Showing drug card for Simvastatin (DB00641)

• APRD00104

• Approved
• Small Molecule

1. Simvastatin [Usan:Ban:Inn]
2. Simvastatina [Spanish]
3. Simvastatine [French]
4. Simvastatinum [Latin]

1. Cholestat
2. Coledis
3. Colemin
4. Corolin
5. Denan
6. Labistatin
7. Lipex
8. Lodales
9. Medipo
10. Nivelipol
11. Pantok
12. Rendapid
13. Simovil
14. Sinvacor
15. Sivastin
16. Synvinolin
17. Vasotenal
18. Vytorin
19. Zocor
20. Zocord

1. Inegy (Simvastatin + Ezetimibe)

• Show PDF (issued on 2002-05-01)

• Anticholesteremic Agents
• Antilipemic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors

• C10AA01

• 24:06.08

• Avoid alcohol.
• Avoid drastic changes in dietary habit.
• Avoid taking with grapefruit juice.

1. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE: Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007 Jul 19;5:20. [PubMed ]
2. Drugs.com
3. Wikipedia
4. RxList
5. PDRhealth

• Humans and other mammals

1. Cytochrome P450 3A4 (CYP3A4)
2. Cytochrome P450 2C8 (CYP2C8)

1. Prothrombin
2. Matrix metalloproteinase-9
3. Peroxisome proliferator-activated receptor alpha
4. Vascular endothelial growth factor A
5. Plasminogen activator inhibitor 1
6. 3-hydroxy-3-methylglutaryl-coenzyme A reductase
7. Tumor necrosis factor
8. Interleukin-6
9. Interferon gamma
10. Interleukin-8
11. Cytochrome P450 3A3
12. Bone morphogenetic protein 2
13. Integrin beta-2
14. Small inducible cytokine A2
15. Angiotensinogen
16. Mitogen-activated protein kinase 3
17. Leukocyte antigen
18. Intercellular adhesion molecule 1
19. Ras-related C3 botulinum toxin substrate 1
20. Collagen alpha-1(XIII) chain
21. Stromelysin-1
22. Caspase-3
23. Lymphotoxin-beta
24. Transforming protein RhoA
25. Tumor necrosis factor receptor superfamily member 5

ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA

MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV

1. Activated Factor II [IIa]
2. Coagulation factor II
3. EC 3.4.21.5
4. Prothrombin precursor
5. Thrombin

MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC
VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV
NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE
CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA
QAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETG
DGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYI
DGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTEN
DLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHP
VCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDST
RIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKY
GFYTHVFRLKKWIQKVIDQFGE

• Selective cleavage of Arg!Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B INHIBITOR Benzamidine; D-Phe-Pro-Arg-CH2Cl; Nalpha-(2-naphthyl-sulfonyl-glycyl)-D-p-amidinopheyl-alanylpiperadin e; Argatroban

• Kringle (PF00051 )
• Trypsin (PF00089 )
• Gla (PF00594 )

• 1-24

• None

• Secreted protein
• extracellular space

ATGGCGCACGTCCGAGGCTTGCAGCTGCCTGGCTGCCTGGCCCTGGCTGCCCTGTGTAGC
CTTGTGCACAGCCAGCATGTGTTCCTGGCTCCTCAGCAAGCACGGTCGCTGCTCCAGCGG
GTCCGGCGAGCCAACACCTTCTTGGAGGAGGTGCGCAAGGGCAACCTAGAGCGAGAGTGC
GTGGAGGAGACGTGCAGCTACGAGGAGGCCTTCGAGGCTCTGGAGTCCTCCACGGCTACG
GATGTGTTCTGGGCCAAGTACACAGCTTGTGAGACAGCGAGGACGCCTCGAGATAAGCTT
GCTGCATGTCTGGAAGGTAACTGTGCTGAGGGTCTGGGTACGAACTACCGAGGGCATGTG
AACATCACCCGGTCAGGCATTGAGTGCCAGCTATGGAGGAGTCGCTACCCACATAAGCCT
GAAATCAACTCCACTACCCATCCTGGGGCCGACCTACAGGAGAATTTCTGCCGCAACCCC
GACAGCAGCACCACGGGACCCTGGTGCTACACTACAGACCCCACCGTGAGGAGGCAGGAA
TGCAGCATCCCTGTCTGTGGCCAGGATCAAGTCACTGTAGCGATGACTCCACGCTCCGAA
GGCTCCAGTGTGAATCTGTCACCTCCATTGGAGCAGTGTGTCCCTGATCGGGGGCAGCAG
TACCAGGGGCGCCTGGCGGTGACCACACATGGGCTCCCCTGCCTGGCCTGGGCCAGCGCA
CAGGCCAAGGCCCTGAGCAAGCACCAGGACTTCAACTCAGCTGTGCAGCTGGTGGAGAAC
TTCTGCCGCAACCCAGACGGGGATGAGGAGGGCGTGTGGTGCTATGTGGCCGGGAAGCCT
GGCGACTTTGGGTACTGCGACCTCAACTATTGTGAGGAGGCCGTGGAGGAGGAGACAGGA
GATGGGCTGGATGAGGACTCAGACAGGGCCATCGAAGGGCGTACCGCCACCAGTGAGTAC
CAGACTTTCTTCAATCCGAGGACCTTTGGCTCGGGAGAGGCAGACTGTGGGCTGCGACCT
CTGTTCGAGAAGAAGTCGCTGGAGGACAAAACCGAAAGAGAGCTCCTGGAATCCTACATC
GACGGGCGCATTGTGGAGGGCTCGGATGCAGAGATCGGCATGTCACCTTGGCAGGTGATG
CTTTTCCGGAAGAGTCCCCAGGAGCTGCTGTGTGGGGCCAGCCTCATCAGTGACCGCTGG
GTCCTCACCGCCGCCCACTGCCTCCTGTACCCGCCCTGGGACAAGAACTTCACCGAGAAT
GACCTTCTGGTGCGCATTGGCAAGCACTCCCGCACAAGGTACGAGCGAAACATTGAAAAG
ATATCCATGTTGGAAAAGATCTACATCCACCCCAGGTACAACTGGCGGGAGAACCTGGAC
CGGGACATTGCCCTGATGAAGCTGAAGAAGCCTGTTGCCTTCAGTGACTACATTCACCCT
GTGTGTCTGCCCGACAGGGAGACGGCAGCCAGCTTGCTCCAGGCTGGATACAAGGGGCGG
GTGACAGGCTGGGGCAACCTGAAGGAGACGTGGACAGCCAACGTTGGTAAGGGGCAGCCC
AGTGTCCTGCAGGTGGTGAACCTGCCCATTGTGGAGCGGCCGGTCTGCAAGGACTCCACC
CGGATCCGCATCACTGACAACATGTTCTGTGCTGGTTACAAGCCTGATGAAGGGAAACGA
GGGGATGCCTGTGAAGGTGACAGTGGGGGACCCTTTGTCATGAAGAGCCCCTTTAACAAC
CGCTGGTATCAAATGGGCATCGTCTCATGGGGTGAAGGCTGTGACCGGGATGGGAAATAT
GGCTTCTACACACATGTGTTCCGCCTGAAGAAGTGGATACAGAAGGTCATTGATCAGTTT
GGAGAGTAG

1. Guinto ER, Caccia S, Rose T, Futterer K, Waksman G, Di Cera E: Unexpected crucial role of residue 225 in serine proteases. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1852-7. [PubMed ]
2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed ]
3. Iwahana H, Yoshimoto K, Shigekiyo T, Shirakami A, Saito S, Itakura M: Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia. Int J Hematol. 1992 Feb;55(1):93-100. [PubMed ]
4. Miyata T, Aruga R, Umeyama H, Bezeaud A, Guillin MC, Iwanaga S: Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. Biochemistry. 1992 Aug 25;31(33):7457-62. [PubMed ]
5. Morishita E, Saito M, Kumabashiri I, Asakura H, Matsuda T, Yamaguchi K: Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His). Blood. 1992 Nov 1;80(9):2275-80. [PubMed ]
6. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton JW 2nd: The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990 Jul 20;249(4966):277-80. [PubMed ]
7. Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J: The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989 Nov;8(11):3467-75. [PubMed ]
8. Walz DA, Hewett-Emmett D, Seegers WH: Amino acid sequence of human prothrombin fragments 1 and 2. Proc Natl Acad Sci U S A. 1977 May;74(5):1969-72. [PubMed ]
9. Henriksen RA, Mann KG: Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity. Biochemistry. 1989 Mar 7;28(5):2078-82. [PubMed ]
10. Degen SJ, Davie EW: Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987 Sep 22;26(19):6165-77. [PubMed ]
11. 3242619 Henriksen RA, Mann KG: Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382. Biochemistry. 1988 Dec 27;27(26):9160-5.
12. 3567158 Miyata T, Morita T, Inomoto T, Kawauchi S, Shirakami A, Iwanaga S: Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima. Biochemistry. 1987 Feb 24;26(4):1117-22.
13. 3759958 Rabiet MJ, Blashill A, Furie B, Furie BC: Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma. J Biol Chem. 1986 Oct 5;261(28):13210-5.
14. 3771562 Rabiet MJ, Furie BC, Furie B: Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273. J Biol Chem. 1986 Nov 15;261(32):15045-8.
15. 3801671 Inomoto T, Shirakami A, Kawauchi S, Shigekiyo T, Saito S, Miyoshi K, Morita T, Iwanaga S: Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin. Blood. 1987 Feb;69(2):565-9.
16. 6305407 Degen SJ, MacGillivray RT, Davie EW: Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. Biochemistry. 1983 Apr 26;22(9):2087-97.
17. 6405779 Board PG, Shaw DC: Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site. Br J Haematol. 1983 Jun;54(2):245-54.
18. 7792730 Degen SJ, McDowell SA, Sparks LM, Scharrer I: Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala. Thromb Haemost. 1995 Feb;73(2):203-9.
19. 7865694 James HL, Kim DJ, Zheng DQ, Girolami A: Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site. Blood Coagul Fibrinolysis. 1994 Oct;5(5):841-4.
20. 8071320 Rydel TJ, Yin M, Padmanabhan KP, Blankenship DT, Cardin AD, Correa PE, Fenton JW 2nd, Tulinsky A: Crystallographic structure of human gamma-thrombin. J Biol Chem. 1994 Sep 2;269(35):22000-6.
21. 873923 Butkowski RJ, Elion J, Downing MR, Mann KG: Primary structure of human prethrombin 2 and alpha-thrombin. J Biol Chem. 1977 Jul 25;252(14):4942-57.
22. 9214615 van de Locht A, Bode W, Huber R, Le Bonniec BF, Stone SR, Esmon CT, Stubbs MT: The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin. EMBO J. 1997 Jun 2;16(11):2977-84.

1. Jacobson JR, Dudek SM, Birukov KG, Ye SQ, Grigoryev DN, Girgis RE, Garcia JG: Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol. 2004 May;30(5):662-70. Epub 2003 Nov 20. [PubMed ]
2. Fenton JW 2nd, Brezniak DV, Ofosu FA, Shen GX, Jacobson JR, Garcia JG: Statins and thrombin. Curr Drug Targets Cardiovasc Haematol Disord. 2005 Apr;5(2):115-20. [PubMed ]
3. Yufu T, Hirano K, Bi D, Hirano M, Nishimura J, Iwamoto Y, Kanaide H: Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1506-11. Epub 2005 Apr 28. [PubMed ]
4. Yamakuchi M, Greer JJ, Cameron SJ, Matsushita K, Morrell CN, Talbot-Fox K, Baldwin WM 3rd, Lefer DJ, Lowenstein CJ: HMG-CoA reductase inhibitors inhibit endothelial exocytosis and decrease myocardial infarct size. Circ Res. 2005 Jun 10;96(11):1185-92. Epub 2005 May 19. [PubMed ]
5. Undas A, Celinska-Lowenhoff M, Brummel-Ziedins KE, Brozek J, Szczeklik A, Mann KG: Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1524-5. [PubMed ]

1. 92 kDa gelatinase
2. 92 kDa type IV collagenase
3. EC 3.4.24.35
4. GELB
5. Gelatinase B
6. MMP-9
7. Matrix metalloproteinase-9 precursor

MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTRDGNADGKPCQFPFIFQGQSYS
ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEEPLSKKLFFFSGRQVWVYTGASVLGPRR
LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED

• Cleavage of gelatin types I and V and collagen types IV and V COFACTOR Zinc; Metal; Calcium

• fn2 (PF00040 )
• Hemopexin (PF00045 )
• Peptidase_M10 (PF00413 )
• PG_binding_1 (PF01471 )
• PT (PF04886 )

• 1-19

• None

• Cytoplasmic

ATGAGCCTCTGGCAGCCCCTGGTCCTGGTGCTCCTGGTGCTGGGCTGCTGCTTTGCTGCC
CCCAGACAGCGCCAGTCCACCCTTGTGCTCTTCCCTGGAGACCTGAGAACCAATCTCACC
GACAGGCAGCTGGCAGAGGAATACCTGTACCGCTATGGTTACACTCGGGTGGCAGAGATG
CGTGGAGAGTCGAAATCTCTGGGGCCTGCGCTGCTGCTTCTCCAGAAGCAACTGTCCCTG
CCCGAGACCGGTGAGCTGGATAGCGCCACGCTGAAGGCCATGCGAACCCCACGGTGCGGG
GTCCCAGACCTGGGCAGATTCCAAACCTTTGAGGGCGACCTCAAGTGGCACCACCACAAC
ATCACCTATTGGATCCAAAACTACTCGGAAGACTTGCCGCGGGCGGTGATTGACGACGCC
TTTGCCCGCGCCTTCGCACTGTGGAGCGCGGTGACGCCGCTCACCTTCACTCGCGTGTAC
AGCCGGGACGCAGACATCGTCATCCAGTTTGGTGTCGCGGAGCACGGAGACGGGTATCCC
TTCGACGGGAAGGACGGGCTCCTGGCACACGCCTTTCCTCCTGGCCCCGGCATTCAGGGA
GACGCCCATTTCGACGATGACGAGTTGTGGTCCCTGGGCAAGGGCGTCGTGGTTCCAACT
CGGTTTGGAAACGCAGATGGCGCGGCCTGCCACTTCCCCTTCATCTTCGAGGGCCGCTCC
TACTCTGCCTGCACCACCGACGGTCGCTCCGACGGCTTGCCCTGGTGCAGTACCACGGCC
AACTACGACACCGACGACCGGTTTGGCTTCTGCCCCAGCGAGAGACTCTACACCCGGGAC
GGCAATGCTGATGGGAAACCCTGCCAGTTTCCATTCATCTTCCAAGGCCAATCCTACTCC
GCCTGCACCACGGACGGTCGCTCCGACGGCTACCGCTGGTGCGCCACCACCGCCAACTAC
GACCGGGACAAGCTCTTCGGCTTCTGCCCGACCCGAGCTGACTCGACGGTGATGGGGGGC
AACTCGGCGGGGGAGCTGTGCGTCTTCCCCTTCACTTTCCTGGGTAAGGAGTACTCGACC
TGTACCAGCGAGGGCCGCGGAGATGGGCGCCTCTGGTGCGCTACCACCTCGAACTTTGAC
AGCGACAAGAAGTGGGGCTTCTGCCCGGACCAAGGATACAGTTTGTTCCTCGTGGCGGCG
CATGAGTTCGGCCACGCGCTGGGCTTAGATCATTCCTCAGTGCCGGAGGCGCTCATGTAC
CCTATGTACCGCTTCACTGAGGGGCCCCCCTTGCATAAGGACGACGTGAATGGCATCCGG
CACCTCTATGGTCCTCGCCCTGAACCTGAGCCACGGCCTCCAACCACCACCACACCGCAG
CCCACGGCTCCCCCGACGGTCTGCCCCACCGGACCCCCCACTGTCCACCCCTCAGAGCGC
CCCACAGCTGGCCCCACAGGTCCCCCCTCAGCTGGCCCCACAGGTCCCCCCACTGCTGGC
CCTTCTACGGCCACTACTGTGCCTTTGAGTCCGGTGGACGATGCCTGCAACGTGAACATC
TTCGACGCCATCGCGGAGATTGGGAACCAGCTGTATTTGTTCAAGGATGGGAAGTACTGG
CGATTCTCTGAGGGCAGGGGGAGCCGGCCGCAGGGCCCCTTCCTTATCGCCGACAAGTGG
CCCGCGCTGCCCCGCAAGCTGGACTCGGTCTTTGAGGAGCCGCTCTCCAAGAAGCTTTTC
TTCTTCTCTGGGCGCCAGGTGTGGGTGTACACAGGCGCGTCGGTGCTGGGCCCGAGGCGT
CTGGACAAGCTGGGCCTGGGAGCCGACGTGGCCCAGGTGACCGGGGCCCTCCGGAGTGGC
AGGGGGAAGATGCTGCTGTTCAGCGGGCGGCGCCTCTGGAGGTTCGACGTGAAGGCGCAG
ATGGTGGATCCCCGGAGCGCCAGCGAGGTGGACCGGATGTTCCCCGGGGTGCCTTTGGAC
ACGCACGACGTCTTCCAGTACCGAGAGAAAGCCTATTTCTGCCAGGACCGCTTCTACTGG
CGCGTGAGTTCCCGGAGTGAGTTGAACCAGGTGGACCAAGTGGGCTACGTGACCTATGAC
ATCCTGCAGTGCCCTGAGGACTAG

1. Zhang B, Henney A, Eriksson P, Hamsten A, Watkins H, Ye S: Genetic variation at the matrix metalloproteinase-9 locus on chromosome 20q12.2-13.1. Hum Genet. 1999 Nov;105(5):418-23. [PubMed ]
2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed ]
3. Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y, Seiki M, Sato H: Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene. 2003 Jul 24;22(30):4617-26. [PubMed ]
4. Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem. 1992 Feb 25;267(6):3581-4. [PubMed ]
5. Masure S, Proost P, Van Damme J, Opdenakker G: Purification and identification of 91-kDa neutrophil gelatinase. Release by the activating peptide interleukin-8. Eur J Biochem. 1991 Jun 1;198(2):391-8. [PubMed ]
6. Van Ranst M, Norga K, Masure S, Proost P, Vandekerckhove F, Auwerx J, Van Damme J, Opdenakker G: The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers. Cytokine. 1991 May;3(3):231-9. [PubMed ]
7. Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem. 1991 Sep 5;266(25):16485-90. [PubMed ]
8. Opdenakker G, Masure S, Grillet B, Van Damme J: Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. Lymphokine Cytokine Res. 1991 Aug;10(4):317-24. [PubMed ]
9. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI: SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989 Oct 15;264(29):17213-21. [PubMed ]
10. Sang QX, Birkedal-Hansen H, Van Wart HE: Proteolytic and non-proteolytic activation of human neutrophil progelatinase B. Biochim Biophys Acta. 1995 Sep 6;1251(2):99-108. [PubMed ]
11. 8426746 Sato H, Seiki M: Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene. 1993 Feb;8(2):395-405.

1. Thunyakitpisal PD, Chaisuparat R: Simvastatin, an HMG-CoA reductase inhibitor, reduced the expression of matrix metalloproteinase-9 (Gelatinase B) in osteoblastic cells and HT1080 fibrosarcoma cells. J Pharmacol Sci. 2004 Apr;94(4):403-9. [PubMed ]
2. Kieseier BC, Archelos JJ, Hartung HP: Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases. Arch Neurol. 2004 Jun;61(6):929-32. [PubMed ]
3. Koh KK, Ahn JY, Jin DK, Han SH, Kim HS, Choi IS, Ahn TH, Shin EK, Jeong EM: Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix metalloproteinase in hyperlipidemia. Int J Cardiol. 2004 Nov;97(2):239-44. [PubMed ]
4. Porter KE, Turner NA, O'Regan DJ, Ball SG: Tumor necrosis factor alpha induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin. Cardiovasc Res. 2004 Dec 1;64(3):507-15. [PubMed ]
5. Liu KZ, Li JB, Lu HL, Wen JK, Han M: [Effects of Astragalus and saponins of Panax notoginseng on MMP-9 in patients with type 2 diabetic macroangiopathy] Zhongguo Zhong Yao Za Zhi. 2004 Mar;29(3):264-6. [PubMed ]

1. PPAR-alpha

MVDTESPLCPLSPLEAGDLESPLSEEFLQEMGNIQEISQSIGEDSSGSFGFTEYQYLGSC
PGSDGSVITDTLSPASSPSSVTYPVVPGSVDESPSGALNIECRICGDKASGYHYGVHACE
GCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGMSHNAIRFGRMPRSE
KAKLKAEILTCEHDIEDSETADLKSLAKRIYEAYLKNFNMNKVKARVILSGKASNNPPFV
IHDMETLCMAEKTLVAKLVANGIQNKEAEVRIFHCCQCTSVETVTELTEFAKAIPGFANL
DLNDQVTLLKYGVYEAIFAMLSSVMNKDGMLVAYGNGFITREFLKSLRKPFCDIMEPKFD
FAMKFNALELDDSDISLFVAAIICCGDRPGLLNVGHIEKMQEGIVHVLRLHLQSNHPDDI
FLFPKLLQKMADLRQLVTEHAQLVQIIKKTESDAALHPLLQEIYRDMY

• Hormone_recep (PF00104 )
• zf-C4 (PF00105 )

• None

• None

• Nucleus

ATGGTGGACACGGAAAGCCCACTCTGCCCCCTCTCCCCACTCGAGGCCGGCGATCTAGAG
AGCCCGTTATCTGAAGAGTTCCTGCAAGAAATGGGAAACATCCAAGAGATTTCGCAATCC
ATCGGCGAGGATAGTTCTGGAAGCTTTGGCTTTACGGAATACCAGTATTTAGGAAGCTGT
CCTGGCTCAGATGGCTCGGTCATCACGGACACGCTTTCACCAGCTTCGAGCCCCTCCTCG
GTGACTTATCCTGTGGTCCCCGGCAGCGTGGACGAGTCTCCCAGTGGAGCATTGAACATC
GAATGTAGAATCTGCGGGGACAAGGCCTCAGGCTATCATTACGGAGTCCACGCGTGTGAA
GGCTGCAAGGGCTTCTTTCGGCGAACGATTCGACTCAAGCTGGTGTATGACAAGTGCGAC
CGCAGCTGCAAGATCCAGAAAAAGAACAGAAACAAATGCCAGTATTGTCGATTTCACAAG
TGCCTTTCTGTCGGGATGTCACACAACGCGATTCGTTTTGGACGAATGCCAAGATCTGAG
AAAGCAAAACTGAAAGCAGAAATTCTTACCTGTGAACATGACATAGAAGATTCTGAAACT
GCAGATCTCAAATCTCTGGCCAAGAGAATCTACGAGGCCTACTTGAAGAACTTCAACATG
AACAAGGTCAAAGCCCGGGTCATCCTCTCAGGAAAGGCCAGTAACAATCCACCTTTTGTC
ATACATGATATGGAGACACTGTGTATGGCTGAGAAGACGCTGGTGGCCAAGCTGGTGGCC
AATGGCATCCAGAACAAGGAGGTGGAGGTCCGCATCTTTCACTGCTGCCAGTGCACGTCA
GTGGAGACCGTCACGGAGCTCACGGAATTCGCCAAGGCCATCCCAGCGTTCGCAAACTTG
GACCTGAACGATCAAGTGACATTGCTAAAATACGGAGTTTATGAGGCCATATTCGCCATG
CTGTCTTCTGTGATGAACAAAGACGGGATGCTGGTAGCGTATGGAAATGGGTTTATAACT
CGTGAATTCCTAAAAAGCCTAAGGAAACCGTTCTGTGATATCATGGAACCCAAGTTTGAT
TTTGCCATGAAGTTCAATGCACTGGAACTGGATGACAGTGATATCTCCCTTTTTGTGGCT
GCTATCATTTGCTGTGGAGATCGTCCTGGCCTTCTAAACGTAGGACACATTGAAAAAATG
CAGGAGGGTATTGTACATGTGCTCAGACTCCACCTGCAGAGCAACCACCCGGACGATATC
TTTCTCTTCCCAAAACTTCTTCAAAAAATGGCAGACCTCCGGCAGCTGGTGACGGAGCAT
GCGCAGCTGGTGCAGATCATCAAGAAGACGGAGTCGGATGCTGCGCTGCACCCGCTACTG
CAGGAGATCTACAGGGACATGTACTGA

1. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed ]
2. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA: Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem. 2000 Feb 25;275(8):5308-17. [PubMed ]
3. Sher T, Yi HF, McBride OW, Gonzalez FJ: cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry. 1993 Jun 1;32(21):5598-604. [PubMed ]
4. Mukherjee R, Jow L, Noonan D, McDonnell DP: Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. J Steroid Biochem Mol Biol. 1994 Nov;51(3-4):157-66. [PubMed ]
5. Tugwood JD, Aldridge TC, Lambe KG, Macdonald N, Woodyatt NJ: Peroxisome proliferator-activated receptors: structures and function. Ann N Y Acad Sci. 1996 Dec 27;804:252-65. [PubMed ]
6. Li H, Gomes PJ, Chen JD: RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8479-84. [PubMed ]

1. Bays H, Stein EA: Pharmacotherapy for dyslipidaemia--current therapies and future agents. Expert Opin Pharmacother. 2003 Nov;4(11):1901-38. [PubMed ]
2. Kleemann R, Verschuren L, de Rooij BJ, Lindeman J, de Maat MM, Szalai AJ, Princen HM, Kooistra T: Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood. 2004 Jun 1;103(11):4188-94. Epub 2004 Feb 19. [PubMed ]
3. Delaney J, Hodson MP, Thakkar H, Connor SC, Sweatman BC, Kenny SP, McGill PJ, Holder JC, Hutton KA, Haselden JN, Waterfield CJ: Tryptophan-NAD+ pathway metabolites as putative biomarkers and predictors of peroxisome proliferation. Arch Toxicol. 2005 Apr;79(4):208-23. Epub 2004 Nov 11. [PubMed ]
4. Myerson M, Ngai C, Jones J, Holleran S, Ramakrishnan R, Berglund L, Ginsberg HN: Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia. J Lipid Res. 2005 Dec;46(12):2735-44. Epub 2005 Sep 14. [PubMed ]
5. Paumelle R, Blanquart C, Briand O, Barbier O, Duhem C, Woerly G, Percevault F, Fruchart JC, Dombrowicz D, Glineur C, Staels B: Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway. Circ Res. 2006 Feb 17;98(3):361-9. Epub 2006 Jan 5. [PubMed ]

1. VEGF-A
2. VPF
3. Vascular endothelial growth factor A precursor
4. Vascular permeability factor

MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR

• PDGF (PF00341 )

• 1-26

• None

• Secreted protein. VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin-binding

ATGAACTTTCTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACCTCCACCAT
GCCAAGTGGTCCCAGGCTGCACCCATGGCAGAAGGAGGAGGGCAGAATCATCACGAAGTG
GTGAAGTTCATGGATGTCTATCAGCGCAGCTACTGCCATCCAATCGAGACCCTGGTGGAC
ATCTTCCAGGAGTACCCTGATGAGATCGAGTACATCTTCAAGCCATCCTGTGTGCCCCTG
ATGCGATGCGGGGGCTGCTGCAATGACGAGGGCCTGGAGTGTGTGCCCACTGAGGAGTCC
AACATCACCATGCAGATTATGCGGATCAAACCTCACCAAGGCCAGCACATAGGAGAGATG
AGCTTCCTACAGCACAACAAATGTGAATGCAGACCAAAGAAAGATAGAGCAAGACAAGAA
AAAAAATCAGTTCGAGGAAAGGGAAAGGGGCAAAAACGAAAGCGCAAGAAATCCCGGTAT
AAGTCCTGGAGCGTGTACGTTGGTGCCCGCTGCTGTCTAATGCCCTGGAGCCTCCCTGGC
CCCCATCCCTGTGGGCCTTGCTCAGAGCGGAGAAAGCATTTGTTTGTACAAGATCCGCAG
ACGTGTAAATGTTCCTGCAAAAACACAGACTCGCGTTGCAAGGCGAGGCAGCTTGAGTTA
AACGAACGTACTTGCAGATGTGACAAGCCGAGGCGGTGA

1. Jingjing L, Xue Y, Agarwal N, Roque RS: Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):752-9. [PubMed ]
2. Whittle C, Gillespie K, Harrison R, Mathieson PW, Harper SJ: Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin Sci (Lond). 1999 Sep;97(3):303-12. [PubMed ]
3. Murphy JF, Fitzgerald DJ: Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor. FASEB J. 2001 Jul;15(9):1667-9. [PubMed ]
4. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed ]
5. Weindel K, Marme D, Weich HA: AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun. 1992 Mar 31;183(3):1167-74. [PubMed ]
6. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947-54. [PubMed ]
7. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW: The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991 Dec;5(12):1806-14. [PubMed ]
8. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989 Dec 8;246(4935):1306-9. [PubMed ]
9. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309-12. [PubMed ]
10. Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J: Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017-24. [PubMed ]
11. 7678805 Fiebich BL, Jager B, Schollmann C, Weindel K, Wilting J, Kochs G, Marme D, Hug H, Weich HA: Synthesis and assembly of functionally active human vascular endothelial growth factor homodimers in insect cells. Eur J Biochem. 1993 Jan 15;211(1-2):19-26.
12. 9054410 Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G: VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem. 1997 Mar 14;272(11):7151-8.
13. 9207067 Muller YA, Li B, Christinger HW, Wells JA, Cunningham BC, de Vos AM: Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7192-7.
14. 9336848 Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: 1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor. Protein Sci. 1997 Oct;6(10):2250-60.
15. 9351807 Muller YA, Christinger HW, Keyt BA, de Vos AM: The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding. Structure. 1997 Oct 15;5(10):1325-38.
16. 9450968 Claffey KP, Shih SC, Mullen A, Dziennis S, Cusick JL, Abrams KR, Lee SW, Detmar M: Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability. Mol Biol Cell. 1998 Feb;9(2):469-81.
17. 9634701 Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure. 1998 May 15;6(5):637-48.
18. 9878851 Lei J, Jiang A, Pei D: Identification and characterization of a new splicing variant of vascular endothelial growth factor: VEGF183. Biochim Biophys Acta. 1998 Dec 22;1443(3):400-6.
19. 9922142 Wiesmann C, Christinger HW, Cochran AG, Cunningham BC, Fairbrother WJ, Keenan CJ, Meng G, de Vos AM: Crystal structure of the complex between VEGF and a receptor-blocking peptide. Biochemistry. 1998 Dec 22;37(51):17765-72.

1. Takenaka M, Hirade K, Tanabe K, Akamatsu S, Dohi S, Matsuno H, Kozawa O: Simvastatin stimulates VEGF release via p44/p42 MAP kinase in vascular smooth muscle cells. Biochem Biophys Res Commun. 2003 Jan 31;301(1):198-203. [PubMed ]
2. Maeda T, Kawane T, Horiuchi N: Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology. 2003 Feb;144(2):681-92. [PubMed ]
3. Matsuno H, Takei M, Hayashi H, Nakajima K, Ishisaki A, Kozawa O: Simvastatin enhances the regeneration of endothelial cells via VEGF secretion in injured arteries. J Cardiovasc Pharmacol. 2004 Mar;43(3):333-40. [PubMed ]
4. Miyahara S, Kiryu J, Yamashiro K, Miyamoto K, Hirose F, Tamura H, Katsuta H, Nishijima K, Tsujikawa A, Honda Y: Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes. Am J Pathol. 2004 May;164(5):1697-706. [PubMed ]
5. Maeda T, Matsunuma A, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N: Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem. 2004 Jun 1;92(3):458-71. [PubMed ]

1. Endothelial plasminogen activator inhibitor
2. PAI
3. PAI-1
4. Plasminogen activator inhibitor 1 precursor

MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP

• Serpin (PF00079 )

• 1-23

• None

• Secreted protein

ATGCAGATGTCTCCAGCCCTCACCTGCCTAGTCCTGGGCCTGGCCCTTGTCTTTGGTGAA
GGGTCTGCTGTGCACCATCCCCCATCCTACGTGGCCCACCTGGCCTCAGACTTCGGGGTG
AGGGTGTTTCAGCAGGTGGCGCAGGCCTCCAAGGACCGCAACGTGGTTTTCTCACCCTAT
GGGGTGGCCTCGGTGTTGGCCATGCTCCAGCTGACAACAGGAGGAGAAACCCAGCAGCAG
ATTCAAGCAGCTATGGGATTCAAGATTGATGACAAGGGCATGGCCCCCGCCCTCCGGCAT
CTGTACAAGGAGCTCATGGGGCCATGGAACAAGGACGAGATCAGCACCACAGACGCGATC
TTCGTCCAGCGGGATCTGAAGCTGGTCCAGGGCTTCATGCCCCACTTCTTCAGGCTGTTC
CGGAGCACGGTCAAGCAAGTGGACTTTTCAGAGGTGGAGAGAGCCAGATTCATCATCAAT
GACTGGGTGAAGACACACACAAAAGGTATGATCAGCAACTTGCTTGGGAAAGGAGCCGTG
GACCAGCTGACACGGCTGGTGCTGGTGAATGCCCTCTACTTCAACGGCCAGTGGAAGACT
CCCTTCCCCGACTCCAGCACCCACCGCCGCCTCTTCCACAAATCAGACGGCAGCACTGTC
TCTGTGCCCATGATGGCTCAGACCAACAAGTTCAACTATACTGAGTTCACCACGCCCGAT
GGCCATTACTACGACATCCTGGAACTGCCCTACCACGGGGACACCCTCAGCATGTTCATT
GCTGCCCCTTATGAAAAAGAGGTGCCTCTCTCTGCCCTCACCAACATTCTGAGTGCCCAG
CTCATCAGCCACTGGAAAGGCAACATGACCAGGCTGCCCCGCCTCCTGGTTCTGCCCAAG
TTCTCCCTGGAGACTGAAGTCGACCTCAGGAAGCCCCTAGAGAACCTGGGAATGACCGAC
ATGTTCAGACAGTTTCAGGCTGACTTCACGAGTCTTTCAGACCAAGAGCCTCTCCACGTC
GCGCAGGCGCTGCAGAAAGTGAAGATCGAGGTGAACGAGAGTGGCACGGTGGCCTCCTCA
TCCACAGCTGTCATAGTCTCAGCCCGCATGGCCCCCGAGGAGATCATCATGGACAGACCC
TTCCTCTTTGTGGTCCGGCACAACCCCACAGGAACAGTCCTTTTCATGGGCCAAGTGATG
GAACCCTGA

1. Sharp AM, Stein PE, Pannu NS, Carrell RW, Berkenpas MB, Ginsburg D, Lawrence DA, Read RJ: The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion. Structure. 1999 Feb 15;7(2):111-8. [PubMed ]
2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed ]
3. Nar H, Bauer M, Stassen JM, Lang D, Gils A, Declerck PJ: Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation. J Mol Biol. 2000 Mar 31;297(3):683-95. [PubMed ]
4. Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G: The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J Biol Chem. 2001 Aug 3;276(31):28889-96. Epub 2001 May 30. [PubMed ]
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6. Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ: Structural basis of latency in plasminogen activator inhibitor-1. Nature. 1992 Jan 16;355(6357):270-3. [PubMed ]
7. Pannekoek H, Veerman H, Lambers H, Diergaarde P, Verweij CL, van Zonneveld AJ, van Mourik JA: Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. EMBO J. 1986 Oct;5(10):2539-44. [PubMed ]
8. Follo M, Ginsburg D: Structure and expression of the human gene encoding plasminogen activator inhibitor, PAI-1. Gene. 1989 Dec 14;84(2):447-53. [PubMed ]
9. Loskutoff DJ, Linders M, Keijer J, Veerman H, van Heerikhuizen H, Pannekoek H: Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns. Biochemistry. 1987 Jun 30;26(13):3763-8. [PubMed ]
10. Andreasen PA, Riccio A, Welinder KG, Douglas R, Sartorio R, Nielsen LS, Oppenheimer C, Blasi F, Dano K: Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing. FEBS Lett. 1986 Dec 15;209(2):213-8. [PubMed ]
11. 3026837 Wun TC, Kretzmer KK: cDNA cloning and expression in E. coli of a plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell. FEBS Lett. 1987 Jan 1;210(1):11-6.
12. 3092219 Ny T, Sawdey M, Lawrence D, Millan JL, Loskutoff DJ: Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6776-80.
13. 3097076 Ginsburg D, Zeheb R, Yang AY, Rafferty UM, Andreasen PA, Nielsen L, Dano K, Lebo RV, Gelehrter TD: cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest. 1986 Dec;78(6):1673-80.
14. 3132455 Bosma PJ, van den Berg EA, Kooistra T, Siemieniak DR, Slightom JL: Human plasminogen activator inhibitor-1 gene. Promoter and structural gene nucleotide sequences. J Biol Chem. 1988 Jul 5;263(19):9129-41.
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16. 7522053 Sigurdardottir O, Wiman B: Identification of a PAI-1 binding site in vitronectin. Biochim Biophys Acta. 1994 Sep 21;1208(1):104-10.
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19. 9634700 Xue Y, Bjorquist P, Inghardt T, Linschoten M, Musil D, Sjolin L, Deinum J: Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide. Structure. 1998 May 15;6(5):627-36.

1. Haslinger B, Kleemann R, Toet KH, Kooistra T: Simvastatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-alpha-activated human peritoneal mesothelial cells. Kidney Int. 2003 Jun;63(6):2065-74. [PubMed ]
2. Kunieda Y, Nakagawa K, Nishimura H, Kato H, Ukimura N, Yano S, Kawano H, Kimura S, Nakagawa M, Tsuji H: HMG CoA reductase inhibitor suppresses the expression of tissue factor and plasminogen activator inhibitor-1 induced by angiotensin II in cultured rat aortic endothelial cells. Thromb Res. 2003 Jun 1;110(4):227-34. [PubMed ]
3. Skrha J, Stulc T, Hilgertova J, Weiserova H, Kvasnicka J, Ceska R: Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. Eur J Pharmacol. 2004 Jun 16;493(1-3):183-9. [PubMed ]
4. Ludwig S, Dharmalingam S, Erickson-Nesmith S, Ren S, Zhu F, Ma GM, Zhao R, Fenton JW 2nd, Ofosu FA, Velthuis HT, van Mierlo G, Shen GX: Impact of simvastatin on hemostatic and fibrinolytic regulators in Type 2 diabetes mellitus. Diabetes Res Clin Pract. 2005 Nov;70(2):110-8. [PubMed ]
5. Wei J, Ma C, Wang X: Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 expression of glomerular mesangial cells in hypercholesterolemic rabbits. Biomed Res. 2006 Aug;27(4):149-55. [PubMed ]

1. EC 1.1.1.34
2. HMG-CoA reductase

MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA

• (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+

• HMG-CoA_red (PF00368 )

• None

• 10-39
• 57-78
• 90-114
• 124-149
• 160-187
• 192-220
• 315-339

• Endoplasmic reticulum
• endoplasmic reticulum membrane
• multi-pass membrane protein. Peroxisome
• pero

ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC
ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC
AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT
GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC
CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT
TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC
TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA
GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA
ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA
GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA
GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA
GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA
GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG
TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA
AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA
ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT
GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA
CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA
CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG
AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA
AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC
TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG
GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA
TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG
TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC
AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC
TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG
GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT
TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC
AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT
GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG
GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA
CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT
TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT
CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG
GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA
TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT
GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC
TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA
ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA
GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG
CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA
ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA
CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA
GGAGCTTGCACCAAGAAGACAGCCTGA

1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed ]
2. Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [PubMed ]
3. Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [PubMed ]

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed ]
2. Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. [PubMed ]
3. Cenedella RJ, Kuszak JR, Al-Ghoul KJ, Qin S, Sexton PS: Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats. J Lipid Res. 2003 Jan;44(1):198-211. [PubMed ]
4. Stoebner PE, Michot C, Ligeron C, Durand L, Meynadier J, Meunier L: [Simvastatin-induced lichen planus pemphigoides] Ann Dermatol Venereol. 2003 Feb;130(2 Pt 1):187-90. [PubMed ]
5. Pappu AS, Bacon SP, Illingworth DR: Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. J Lab Clin Med. 2003 Apr;141(4):250-6. [PubMed ]
6. Liu L, Zhang R, Zhao JJ, Rogers JD, Hsieh JY, Fang W, Matuszewski BK, Dobrinska MR: Determination of simvastatin-derived HMG-CoA reductase inhibitors in biomatrices using an automated enzyme inhibition assay with radioactivity detection. J Pharm Biomed Anal. 2003 Apr 24;32(1):107-23. [PubMed ]

1. Cachectin
2. TNF-a
3. TNF-alpha
4. Tumor necrosis factor ligand superfamily member 2
5. Tumor necrosis factor precursor

MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL

• TNF (PF00229 )

• None

• 36-56

• Cell membrane
• single-pass type II membrane protein. Processed form:Secreted protein. Also exists as

ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA

1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed ]
2. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, Chaudhri G: A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999 Apr 15;18(8):2119-26. [PubMed ]
3. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed ]
4. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed ]
5. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed ]
6. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed ]
7. Jones EY, Stuart DI, Walker NP: Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225-8. [PubMed ]
8. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed ]
9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed ]
10. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed ]
11. 3883195 Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.
12. 3932069 Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22.
13. 6392892 Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.
14. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.
15. 8597870 Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60.
16. 9034191 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6.
17. 9442056 Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60.
18. 9488135 Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7.

1. Choi M, Rolle S, Rane M, Haller H, Luft FC, Kettritz R: Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA. Kidney Int. 2003 Jan;63(1):96-106. [PubMed ]
2. Rezaie-Majd A, Prager GW, Bucek RA, Schernthaner GH, Maca T, Kress HG, Valent P, Binder BR, Minar E, Baghestanian M: Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):397-403. Epub 2003 Jan 30. [PubMed ]
3. Haslinger B, Kleemann R, Toet KH, Kooistra T: Simvastatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-alpha-activated human peritoneal mesothelial cells. Kidney Int. 2003 Jun;63(6):2065-74. [PubMed ]
4. Zubelewicz-Szkodzinska B, Szkodzinski J, Danikiewicz A, Romanowski W, Blazelonis A, Muc-Wierzgon M, Pietka-Rzycka A, Muryn Z: Effects of simvastatin on pro-inflammatory cytokines in patients with hypercholesterolemia. Kardiol Pol. 2003 Dec;59(12):465-74. [PubMed ]
5. Matsumoto M, Einhaus D, Gold ES, Aderem A: Simvastatin augments lipopolysaccharide-induced proinflammatory responses in macrophages by differential regulation of the c-Fos and c-Jun transcription factors. J Immunol. 2004 Jun 15;172(12):7377-84. [PubMed ]

1. B-cell stimulatory factor 2
2. BSF-2
3. CDF
4. CTL differentiation factor
5. Hybridoma growth factor
6. IL-6
7. Interferon beta-2
8. Interleukin-6 precursor

MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM

• IL6 (PF00489 )

• 1-29

• None

• Secreted protein

ATGAACTCCTTCTCCACAAGCGCCTTCGGTCCAGTTGCCTTCTCCCTGGGGCTGCTCCTG
GTGTTGCCTGCTGCCTTCCCTGCCCCAGTACCCCCAGGAGAAGATTCCAAAGATGTAGCC
GCCCCACACAGACAGCCACTCACCTCTTCAGAACGAATTGACAAACAAATTCGGTACATC
CTCGACGGCATCTCAGCCCTGAGAAAGGAGACATGTAACAAGAGTAACATGTGTGAAAGC
AGCAAAGAGGCACTGGCAGAAAACAACCTGAACCTTCCAAAGATGGCTGAAAAAGATGGA
TGCTTCCAATCTGGATTCAATGAGGAGACTTGCCTGGTGAAAATCATCACTGGTCTTTTG
GAGTTTGAGGTATACCTAGAGTACCTCCAGAACAGATTTGAGAGTAGTGAGGAACAAGCC
AGAGCTGTCCAGATGAGTACAAAAGTCCTGATCCAGTTCCTGCAGAAAAAGGCAAAGAAT
CTAGATGCAATAACCACCCCTGACCCAACCACAAATGCCAGCCTGCTGACGAAGCTGCAG
GCACAGAACCAGTGGCTGCAGGACATGACAACTCATCTCATTCTGCGCAGCTTTAAGGAG
TTCCTGCAGTCCAGCCTGAGGGCTCTTCGGCAAATGTAG

1. Chen QY: [Stable and efficient expression of human interleukin-6 cDNA in mammalian cells after gene transfer] Zhonghua Zhong Liu Za Zhi. 1992 Sep;14(5):340-4. [PubMed ]
2. May LT, Shaw JE, Khanna AK, Zabriskie JB, Sehgal PB: Marked cell-type-specific differences in glycosylation of human interleukin-6. Cytokine. 1991 May;3(3):204-11. [PubMed ]
3. Lutticken C, Kruttgen A, Moller C, Heinrich PC, Rose-John S: Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6. FEBS Lett. 1991 May 6;282(2):265-7. [PubMed ]
4. Clogston CL, Boone TC, Crandall BC, Mendiaz EA, Lu HS: Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor. Arch Biochem Biophys. 1989 Jul;272(1):144-51. [PubMed ]
5. Ming JE, Cernetti C, Steinman RM, Granelli-Piperno A: Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. J Mol Cell Immunol. 1989;4(4):203-11; discussion 211-2. [PubMed ]
6. Tonouchi N, Miwa K, Karasuyama H, Matsui H: Deletion of 3' untranslated region of human BSF-2 mRNA causes stabilization of the mRNA and high-level expression in mouse NIH3T3 cells. Biochem Biophys Res Commun. 1989 Sep 15;163(2):1056-62. [PubMed ]
7. Zilberstein A, Ruggieri R, Korn JH, Revel M: Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 1986 Oct;5(10):2529-37. [PubMed ]
8. Wong GG, Witek-Giannotti J, Hewick RM, Clark SC, Ogawa M: Interleukin 6: identification as a hematopoietic colony-stimulating factor. Behring Inst Mitt. 1988 Aug;(83):40-7. [PubMed ]
9. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau A: Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6. J Immunol. 1988 Mar 1;140(5):1534-41. [PubMed ]
10. Brakenhoff JP, de Groot ER, Evers RF, Pannekoek H, Aarden LA: Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol. 1987 Dec 15;139(12):4116-21. [PubMed ]
11. 3491322 Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, et al.: Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6-12;324(6092):73-6.
12. 3500852 Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T: Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J. 1987 Oct;6(10):2939-45.
13. 3538015 May LT, Helfgott DC, Sehgal PB: Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957-61.
14. 3758081 Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W: Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem. 1986 Sep 15;159(3):625-32.
15. 7851440 Breton J, La Fiura A, Bertolero F, Orsini G, Valsasina B, Ziliotto R, De Filippis V, Polverino de Laureto P, Fontana A: Structure, stability and biological properties of a N-terminally truncated form of recombinant human interleukin-6 containing a single disulfide bond. Eur J Biochem. 1995 Jan 15;227(1-2):573-81.
16. 8555185 Nishimura C, Watanabe A, Gouda H, Shimada I, Arata Y: Folding topologies of human interleukin-6 and its mutants as studied by NMR spectroscopy. Biochemistry. 1996 Jan 9;35(1):273-81.
17. 9118960 Somers W, Stahl M, Seehra JS: 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J. 1997 Mar 3;16(5):989-97.
18. 9159484 Xu GY, Yu HA, Hong J, Stahl M, McDonagh T, Kay LE, Cumming DA: Solution structure of recombinant human interleukin-6. J Mol Biol. 1997 May 2;268(2):468-81.

1. Li JJ, Chen XJ: Simvastatin inhibits interleukin-6 release in human monocytes stimulated by C-reactive protein and lipopolysaccharide. Coron Artery Dis. 2003 Jun;14(4):329-34. [PubMed ]
2. Li JJ, Fang CH: C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004;62(4):499-506. [PubMed ]
3. Guillen C, de Gortazar AR, Esbrit P: The interleukin-6/soluble interleukin-6 receptor system induces parathyroid hormone-related protein in human osteoblastic cells. Calcif Tissue Int. 2004 Aug;75(2):153-9. Epub 2004 Apr 29. [PubMed ]
4. Tikiz C, Unlu Z, Tikiz H, Ay K, Angin A, Onur E, Var A, Tuzun C: The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters. J Bone Miner Metab. 2004;22(4):365-71. [PubMed ]
5. Gronich N, Drucker L, Shapiro H, Radnay J, Yarkoni S, Lishner M: Simvastatin induces death of multiple myeloma cell lines. J Investig Med. 2004 Jul;52(5):335-44. [PubMed ]

1. IFN-gamma
2. Immune interferon
3. Interferon gamma precursor

MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ

• IFN-gamma (PF00714 )

• 1-23

• None

• Secreted protein

ATGAAATATACAAGTTATATCTTGGCTTTTCAGCTCTGCATCGTTTTGGGTTCTCTTGGC
TGTTACTGCCAGGACCCATATGTAAAAGAAGCAGAAAACCTTAAGAAATATTTTAATGCA
GGTCATTCAGATGTAGCGGATAATGGAACTCTTTTCTTAGGCATTTTGAAGAATTGGAAA
GAGGAGAGTGACAGAAAAATAATGCAGAGCCAAATTGTCTCCTTTTACTTCAAACTTTTT
AAAAACTTTAAAGATGACCAGAGCATCCAAAAGAGTGTGGAGACCATCAAGGAAGACATG
AATGTCAAGTTTTTCAATAGCAACAAAAAGAAACGAGATGACTTCGAAAAGCTGACTAAT
TATTCGGTAACTGACTTGAATGTCCAACGCAAAGCAATACATGAACTCATCCAAGTGATG
GCTGAACTGTCGCCAGCAGCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTTCAA
GGTCGAAGAGCATCCCAGTAA

1. Landar A, Curry B, Parker MH, DiGiacomo R, Indelicato SR, Nagabhushan TL, Rizzi G, Walter MR: Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma. J Mol Biol. 2000 May 26;299(1):169-79. [PubMed ]
2. Grzesiek S, Dobeli H, Gentz R, Garotta G, Labhardt AM, Bax A: 1H, 13C, and 15N NMR backbone assignments and secondary structure of human interferon-gamma. Biochemistry. 1992 Sep 8;31(35):8180-90. [PubMed ]
3. Ealick SE, Cook WJ, Vijay-Kumar S, Carson M, Nagabhushan TL, Trotta PP, Bugg CE: Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702. [PubMed ]
4. Yamamoto S, Hase S, Yamauchi H, Tanimoto T, Ikenaka T: Studies on the sugar chains of interferon-gamma from human peripheral-blood lymphocytes. J Biochem (Tokyo). 1989 Jun;105(6):1034-9. [PubMed ]
5. Nishi T, Fujita T, Nishi-Takaoka C, Saito A, Matsumoto T, Sato M, Oka T, Itoh S, Yip YK, Vilcek J, et al.: Cloning and expression of a novel variant of human interferon-gamma cDNA. J Biochem (Tokyo). 1985 Jan;97(1):153-9. [PubMed ]
6. Pan YC, Stern AS, Familletti PC, Khan FR, Chizzonite R: Structural characterization of human interferon gamma. Heterogeneity of the carboxyl terminus. Eur J Biochem. 1987 Jul 1;166(1):145-9. [PubMed ]
7. Gray PW, Leung DW, Pennica D, Yelverton E, Najarian R, Simonsen CC, Derynck R, Sherwood PJ, Wallace DM, Berger SL, Levinson AD, Goeddel DV: Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503-8. [PubMed ]
8. Devos R, Cheroutre H, Taya Y, Degrave W, Van Heuverswyn H, Fiers W: Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells. Nucleic Acids Res. 1982 Apr 24;10(8):2487-501. [PubMed ]
9. Gray PW, Goeddel DV: Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63. [PubMed ]
10. Taya Y, Devos R, Tavernier J, Cheroutre H, Engler G, Fiers W: Cloning and structure of the human immune interferon-gamma chromosomal gene. EMBO J. 1982;1(8):953-8. [PubMed ]
11. 6427223 Rinderknecht E, O'Connor BH, Rodriguez H: Natural human interferon-gamma. Complete amino acid sequence and determination of sites of glycosylation. J Biol Chem. 1984 Jun 10;259(11):6790-7.
12. 7617032 Walter MR, Windsor WT, Nagabhushan TL, Lundell DJ, Lunn CA, Zauodny PJ, Narula SK: Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. Nature. 1995 Jul 20;376(6537):230-5.

1. McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY: A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. J Immunol. 2004 Mar 1;172(5):2903-8. [PubMed ]
2. Bessler H, Salman H, Bergman M, Straussberg R, Djaldetti M: In vitro effect of statins on cytokine production and mitogen response of human peripheral blood mononuclear cells. Clin Immunol. 2005 Oct;117(1):73-7. [PubMed ]
3. Buttice G, Miller J, Wang L, Smith BD: Interferon-gamma induces major histocompatibility class II transactivator (CIITA), which mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells. Circ Res. 2006 Mar 3;98(4):472-9. Epub 2006 Jan 26. [PubMed ]
4. Coward WR, Marei A, Yang A, Vasa-Nicotera MM, Chow SC: Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes. J Immunol. 2006 May 1;176(9):5284-92. [PubMed ]
5. Zeinstra E, Wilczak N, Chesik D, Glazenburg L, Kroese FG, De Keyser J: Simvastatin inhibits interferon-gamma-induced MHC class II up-regulation in cultured astrocytes. J Neuroinflammation. 2006 Jul 21;3:16. [PubMed ]

1. CXCL8
2. Emoctakin
3. GCP-1
4. Granulocyte chemotactic protein 1
5. IL-8
6. Interleukin-8 precursor
7. MDNCF
8. MONAP
9. Monocyte-derived neutrophil chemotactic factor
10. Monocyte-derived neutrophil-activating peptide
11. NAP-1
12. Neutrophil- activating protein 1
13. Protein 3-10C
14. T-cell chemotactic factor

MTSKLAVALLAAFLISAALCEGAVLPRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPH
CANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENS

• IL8 (PF00048 )

• 1-20

• None

• Secreted protein

ATGACTTCCAAGCTGGCCGTGGCTCTCTTGGCAGCCTTCCTGATTTCTGCAGCTCTGTGT
GAAGGTGCAGTTTTGCCAAGGAGTGCTAAAGAACTTAGATGTCAGTGCATAAAGACATAC
TCCAAACCTTTCCACCCCAAATTTATCAAAGAACTGAGAGTGATTGAGAGTGGACCACAC
TGCGCCAACACAGAAATTATTGTAAAGCTTTCTGATGGAAGAGAGCTCTGTCTGGACCCC
AAGGAAAACTGGGTGCAGAGGGTTGTGGAGAAGTTTTTGAAGAGGGCTGAGAATTCATAA

1. Skelton NJ, Quan C, Reilly D, Lowman H: Structure of a CXC chemokine-receptor fragment in complex with interleukin-8. Structure. 1999 Feb 15;7(2):157-68. [PubMed ]
2. Gerber N, Lowman H, Artis DR, Eigenbrot C: Receptor-binding conformation of the "ELR" motif of IL-8: X-ray structure of the L5C/H33C variant at 2.35 A resolution. Proteins. 2000 Mar 1;38(4):361-7. [PubMed ]
3. Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G: Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood. 2000 Oct 15;96(8):2673-81. [PubMed ]
4. Baggiolini M, Clark-Lewis I: Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992 Jul 27;307(1):97-101. [PubMed ]
5. Baldwin ET, Weber IT, St Charles R, Xuan JC, Appella E, Yamada M, Matsushima K, Edwards BF, Clore GM, Gronenborn AM, et al.: Crystal structure of interleukin 8: symbiosis of NMR and crystallography. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):502-6. [PubMed ]
6. Clore GM, Gronenborn AM: Comparison of the solution nuclear magnetic resonance and crystal structures of interleukin-8. Possible implications for the mechanism of receptor binding. J Mol Biol. 1991 Feb 20;217(4):611-20. [PubMed ]
7. Clark-Lewis I, Moser B, Walz A, Baggiolini M, Scott GJ, Aebersold R: Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry. 1991 Mar 26;30(12):3128-35. [PubMed ]
8. Van Damme J, Rampart M, Conings R, Decock B, Van Osselaer N, Willems J, Billiau A: The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. Eur J Immunol. 1990 Sep;20(9):2113-8. [PubMed ]
9. Baldwin ET, Franklin KA, Appella E, Yamada M, Matsushima K, Wlodawer A, Weber IT: Crystallization of human interleukin-8. A protein chemotactic for neutrophils and T-lymphocytes. J Biol Chem. 1990 Apr 25;265(12):6851-3. [PubMed ]
10. Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM: Three-dimensional structure of interleukin 8 in solution. Biochemistry. 1990 Feb 20;29(7):1689-96. [PubMed ]
11. 2212672 Hebert CA, Luscinskas FW, Kiely JM, Luis EA, Darbonne WC, Bennett GL, Liu CC, Obin MS, Gimbrone MA Jr, Baker JB: Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol. 1990 Nov 1;145(9):3033-40.
12. 2523801 Van Damme J, Van Beeumen J, Conings R, Decock B, Billiau A: Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of beta-thromboglobulin. Eur J Biochem. 1989 May 1;181(2):337-44.
13. 2648135 Yoshimura T, Robinson EA, Appella E, Matsushima K, Showalter SD, Skeel A, Leonard EJ: Three forms of monocyte-derived neutrophil chemotactic factor (MDNCF) distinguished by different lengths of the amino-terminal sequence. Mol Immunol. 1989 Jan;26(1):87-93.
14. 2655583 Golds EE, Mason P, Nyirkos P: Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells and fibroblasts. Biochem J. 1989 Apr 15;259(2):585-8.
15. 2659722 Suzuki K, Miyasaka H, Ota H, Yamakawa Y, Tagawa M, Kuramoto A, Mizuno S: Purification and partial primary sequence of a chemotactic protein for polymorphonuclear leukocytes derived from human lung giant cell carcinoma LU65C cells. J Exp Med. 1989 Jun 1;169(6):1895-901.
16. 2663993 Mukaida N, Shiroo M, Matsushima K: Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366-71.
17. 2664463 Kowalski J, Denhardt DT: Regulation of the mRNA for monocyte-derived neutrophil-activating peptide in differentiating HL60 promyelocytes. Mol Cell Biol. 1989 May;9(5):1946-57.
18. 2681204 Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM: Determination of the secondary structure of interleukin-8 by nuclear magnetic resonance spectroscopy. J Biol Chem. 1989 Nov 15;264(32):18907-11.
19. 2953813 Schmid J, Weissmann C: Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250-6.
20. 3260265 Matsushima K, Morishita K, Yoshimura T, Lavu S, Kobayashi Y, Lew W, Appella E, Kung HF, Leonard EJ, Oppenheim JJ: Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883-93.
21. 3279957 Gregory H, Young J, Schroder JM, Mrowietz U, Christophers E: Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP). Biochem Biophys Res Commun. 1988 Mar 15;151(2):883-90.
22. 3322281 Walz A, Peveri P, Aschauer H, Baggiolini M: Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun. 1987 Dec 16;149(2):755-61.
23. 3480540 Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ: Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233-7.
24. 8631339 Sticht H, Auer M, Schmitt B, Besemer J, Horcher M, Kirsch T, Lindley IJ, Rosch P: Structure and activity of a chimeric interleukin-8-melanoma-growth-stimulatory-activity protein. Eur J Biochem. 1996 Jan 15;235(1-2):26-35.

1. Hernandez-Presa MA, Ortego M, Tunon J, Martin-Ventura JL, Mas S, Blanco-Colio LM, Aparicio C, Ortega L, Gomez-Gerique J, Vivanco F, Egido J: Simvastatin reduces NF-kappaB activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet. Cardiovasc Res. 2003 Jan;57(1):168-77. [PubMed ]
2. Waehre T, Damas JK, Gullestad L, Holm AM, Pedersen TR, Arnesen KE, Torsvik H, Froland SS, Semb AG, Aukrust P: Hydroxymethylglutaryl coenzyme a reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease. J Am Coll Cardiol. 2003 May 7;41(9):1460-7. [PubMed ]
3. Panichi V, Paoletti S, Mantuano E, Manca-Rizza G, Filippi C, Santi S, Taccola D, Donadio C, Tramonti G, Innocenti M, Casto G, Consani C, Sbragia G, Franzoni F, Galetta F, Panicucci E, Barsotti G: In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients. Nephrol Dial Transplant. 2006 Feb;21(2):337-44. Epub 2005 Oct 25. [PubMed ]
4. Yokota K, Miyazaki T, Hirano M, Akiyama Y, Mimura T: Simvastatin inhibits production of interleukin 6 (IL-6) and IL-8 and cell proliferation induced by tumor necrosis factor-alpha in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Rheumatol. 2006 Mar;33(3):463-71. [PubMed ]
5. Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y: Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006 Jun;85(6):520-3. [PubMed ]

1. CYPIIIA3
2. EC 1.14.14.1
3. HLp

MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF
DMECHKKYGKVWGFYDGQQPVLAITDPDMIKLVLVKECYSVFTNREPFGPVGFMKSAISI
AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRRERETGKPVTLKDVFGAYS
MDVITSSSFGVNVDSLNNPQDPLVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV
FPREVTNFLRKAVKRMKESRLEDTQKHRVDFLQLMIDSHKNSKETESHKALSDLELVAQS
IIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMV
VNETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERF
SKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSL
GGLLQPEKPVVLKVESRDGTVSGA

• RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O

• p450 (PF00067 )

• None

• None

• Endoplasmic reticulum
• endoplasmic reticulum membrane
• peripheral membrane protein

ATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGTCAGCCTGGTG
CTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGGAATTCCAGGG
CCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTTTTGTATGTTT
GACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGGTCAACAGCCT
GTGCTGGCTATCACAGATCCTGACATGATCAAACTAGTGCTAGTGAAAGAATGTTATTCT
GTCTTCACAAACCGCGAGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGCCATCTCTATA
GCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTTCACCAGTGGA
AAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGTGAGAAATCTG
AGGCGGGAACGAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGGGGCCTACAGC
ATGGATGTGATCACTAGCTCATCATTTGGAGTGAACGTCGACTCTCTCAACAATCCACAG
GACCCCCTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGATCCATTCTTT
CTCTCAATAACAGTCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAATATCTGTGTG
TTTCCAAGAGAAGTTACAAATTTTTTAAGAAAAGCTGTAAAAAGGATGAAAGAAAGTCGC
CTCGAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGACTCTCATAAG
AATTCAAAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGCCCAATCA
ATTATCTTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCATTATGTAT
GAACTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGCAGTTTTA
CCCAATAAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGACATGGTG
GTGAATGAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTGCAAAAAA
GATGTTGAGATCAATGGGATGTTCATTCCCAAAGGGTGGGTGGTGATGATTCCAAGCTAT
GCTCTTCACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGAAAGATTC
AGCAAGAAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCC
AGAAACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAATCAGAGTC
CTTCAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATTAAGCTTA
GGAGGACTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGATGGCACC
GTAAGTGGAGCCTGA

1. Molowa DT, Schuetz EG, Wrighton SA, Watkins PB, Kremers P, Mendez-Picon G, Parker GA, Guzelian PS: Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5311-5. [PubMed ]
2. Watkins PB, Wrighton SA, Maurel P, Schuetz EG, Mendez-Picon G, Parker GA, Guzelian PS: Identification of an inducible form of cytochrome P-450 in human liver. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6310-4. [PubMed ]

1. Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. [PubMed ]
2. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed ]
3. Dingemanse J, Schaarschmidt D, van Giersbergen PL: Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301. [PubMed ]
4. Hatorp V, Hansen KT, Thomsen MS: Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol. 2003 Jun;43(6):649-60. [PubMed ]
5. Becquemont L: [Drug interactions with antilipemics] Therapie. 2003 Jan-Feb;58(1):85-90. [PubMed ]

1. BMP-2
2. BMP-2A
3. Bone morphogenetic protein 2 precursor

MVAGTRCLLALLLPQVLLGGAAGLVPELGRRKFAAASSGRPSSQPSDEVLSEFELRLLSM
FGLKQRPTPSRDAVVPPYMLDLYRRHSGQPGSPAPDHRLERAASRANTVRSFHHEESLEE
LPETSGKTTRRFFFNLSSIPTEEFITSAELQVFREQMQDALGNNSSFHHRINIYEIIKPA
TANSKFPVTRLLDTRLVNQNASRWESFDVTPAVMRWTAQGHANHGFVVEVAHLEEKQGVS
KRHVRISRSLHQDEHSWSQIRPLLVTFGHDGKGHPLHKREKRQAKHKQRKRLKSSCKRHP
LYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKAC
CVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR

• TGF_beta (PF00019 )
• TGFb_propeptide (PF00688 )

• 1-23

• None

• Secreted protein

ATGGTGGCCGGGACCCGCTGTCTTCTAGCGTTGCTGCTTCCCCAGGTCCTCCTGGGCGGC
GCGGCTGGCCTCGTTCCGGAGCTGGGCCGCAGGAAGTTCGCGGCGGCGTCGTCGGGCCGC
CCCTCATCCCAGCCCTCTGACGAGGTCCTGAGCGAGTTCGAGTTGCGGCTGCTCAGCATG
TTCGGCCTGAAACAGAGACCCACCCCCAGCAGGGACGCCGTGGTGCCCCCCTACATGCTA
GACCTGTATCGCAGGCACTCAGGTCAGCCGGGCTCACCCGCCCCAGACCACCGGTTGGAG
AGGGCAGCCAGCCGAGCCAACACTGTGCGCAGCTTCCACCATGAAGAATCTTTGGAAGAA
CTACCAGAAACGAGTGGGAAAACAACCCGGAGATTCTTCTTTAATTTAAGTTCTATCCCC
ACGGAGGAGTTTATCACCTCAGCAGAGCTTCAGGTTTTCCGAGAACAGATGCAAGATGCT
TTAGGAAACAATAGCAGTTTCCATCACCGAATTAATATTTATGAAATCATAAAACCTGCA
ACAGCCAACTCGAAATTCCCCGTGACCAGACTTTTGGACACCAGGTTGGTGAATCAGAAT
GCAAGCAGGTGGGAAAGTTTTGATGTCACCCCCGCTGTGATGCGGTGGACTGCACAGGGA
CACGCCAACCATGGATTCGTGGTGGAAGTGGCCCACTTGGAGGAGAAACAAGGTGTCTCC
AAGAGACATGTTAGGATAAGCAGGTCTTTGCACCAAGATGAACACAGCTGGTCACAGATA
AGGCCATTGCTAGTAACTTTTGGCCATGATGGAAAAGGGCATCCTCTCCACAAAAGAGAA
AAACGTCAAGCCAAACACAAACAGCGGAAACGCCTTAAGTCCAGCTGTAAGAGACACCCT
TTGTACGTGGACTTCAGTGACGTGGGGTGGAATGACTGGATTGTGGCTCCCCCGGGGTAT
CACGCCTTTTACTGCCACGGAGAATGCCCTTTTCCTCTGGCTGATCATCTGAACTCCACT
AATCATGCCATTGTTCAGACGTTGGTCAACTCTGTTAACTCTAAGATTCCTAAGGCATGC
TGTGTCCCGACAGAACTCAGTGCTATCTCGATGCTGTACCTTGACGAGAATGAAAAGGTT
GTATTAAAGAACTATCAGGACATGGTTGTGGAGGGTTGTGGGTGTCGCTAG

1. Scheufler C, Sebald W, Hulsmeyer M: Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution. J Mol Biol. 1999 Mar 19;287(1):103-15. [PubMed ]
2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed ]
3. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA: Novel regulators of bone formation: molecular clones and activities. Science. 1988 Dec 16;242(4885):1528-34. [PubMed ]

1. Skoglund B, Forslund C, Aspenberg P: Simvastatin improves fracture healing in mice. J Bone Miner Res. 2002 Nov;17(11):2004-8. [PubMed ]
2. Song CL, Dang GT, Guo ZQ: [Effect of simvastatin on bone morphogenetic protein-2 expression and alkaline phosphatase activity of bone marrow stromal cell] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2002 Nov;16(6):384-7. [PubMed ]
3. Song C, Guo Z, Ma Q, Chen Z, Liu Z, Jia H, Dang G: Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem Biophys Res Commun. 2003 Aug 29;308(3):458-62. [PubMed ]
4. Maeda T, Matsunuma A, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N: Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem. 2004 Jun 1;92(3):458-71. [PubMed ]
5. Fromigue O, Hay E, Modrowski D, Bouvet S, Jacquel A, Auberger P, Marie PJ: RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation. Cell Death Differ. 2006 Nov;13(11):1845-56. Epub 2006 Feb 10. [PubMed ]

1. CD18 antigen
2. Cell surface adhesion glycoproteins LFA- 1/CR3/p150,95 subunit beta
3. Complement receptor C3 subunit beta
4. Integrin beta-2 precursor

MLGLRPPLLALVGLLSLGCVLSQECTKFKVSSCRECIESGPGCTWCQKLNFTGPGDPDSI
RCDTRPQLLMRGCAADDIMDPTSLAETQEDHNGGQKQLSPQKVTLYLRPGQAAAFNVTFR
RAKGYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFV
NTHPDKLRNPCPNKEKECQPPFAFRHVLKLTNNSNQFQTEVGKQLISGNLDAPEGGLDAM
MQVAACPEEIGWRNVTRLLVFATDDGFHFAGDGKLGAILTPNDGRCHLEDNLYKRSNEFD
YPSVGQLAHKLAENNIQPIFAVTSRMVKTYEKLTEIIPKSAVGELSEDSSNVVQLIKNAY
NKLSSRVFLDHNALPDTLKVTYDSFCSNGVTHRNQPRGDCDGVQINVPITFQVKVTATEC
IQEQSFVIRALGFTDIVTVQVLPQCECRCRDQSRDRSLCHGKGFLECGICRCDTGYIGKN
CECQTQGRSSQELEGSCRKDNNSIICSGLGDCVCGQCLCHTSDVPGKLIYGQYCECDTIN
CERYNGQVCGGPGRGLCFCGKCRCHPGFEGSACQCERTTEGCLNPRRVECSGRGRCRCNV
CECHSGYQLPLCQECPGCPSPCGKYISCAECLKFEKGPFGKNCSAACPGLQLSNNPVKGR
TCKERDSEGCWVAYTLEQQDGMDRYLIYVDESRECVAGPNIAAIVGGTVAGIVLIGILLL
VIWKALIHLSDLREYRRFEKEKLKSQWNNDNPLFKSATTTVMNPKFAES

• Integrin_beta (PF00362 )
• Integrin_B_tail (PF07965 )
• EGF_2 (PF07974 )
• Integrin_b_cyt (PF08725 )

• 1-22

• 701-723

• Membrane
• single-pass type I membrane protein

ATGCTGGGCCTGCGCCCCCCACTGCTCGCCCTGGTGGGGCTGCTCTCCCTCGGGTGCGTC
CTCTCTCAGGAGTGCACGAAGTTCAAGGTCAGCAGCTGCCGGGAATGCATCGAGTCGGGG
CCCGGCTGCACCTGGTGCCAGAAGCTGAACTTCACAGGGCCGGGGGATCCTGACTCCATT
CGCTGCGACACCCGGCCACAGCTGCTCATGAGGGGCTGTGCGGCTGACGACATCATGGAC
CCCACAAGCCTCGCTGAAACCCAGGAAGACCACAATGGGGGCCAGAAGCAGCTGTCCCCA
CAAAAAGTGACGCTTTACCTGCGACCAGGCCAGGCAGCAGCGTTCAACGTGACCTTCCGG
CGGGCCAAGGGCTACCCCATCGACCTGTACTATCTGATGGACCTCTCCTACTCCATGCTT
GATGACCTCAGGAATGTCAAGAAGCTAGGTGGCGACCTGCTCCGGGCCCTCAACGAGATC
ACCGAGTCCGGCCGCATTGGCTTCGGGTCCTTCGTGGACAAGACCGTGCTGCCGTTCGTG
AACACGCACCCTGATAAGCTGCGAAACCCATGCCCCAACAAGGAGAAAGAGTGCCAGCCC
CCGTTTGCCTTCAGGCACGTGCTGAAGCTGACCAACAACTCCAACCAGTTTCAGACCGAG
GTCGGGAAGCAGCTGATTTCCGGAAACCTGGATGCACCCGAGGGTGGGCTGGACGCCATG
ATGCAGGTCGCCGCCTGCCCGGAGGAAATCGGCTGGCGCAACGTCACGCGGCTGCTGGTG
TTTGCCACTGATGACGGCTTCCATTTCGCGGGCGACGGAAAGCTGGGCGCCATCCTGACC
CCCAACGACGGCCGCTGTCACCTGGAGGACAACTTGTACAAGAGGAGCAACGAATTCGAC
TACCCATCGGTGGGCCAGCTGGCGCACAAGCTGGCTGAAAACAACATCCAGCCCATCTTC
GCGGTGACCAGTAGGATGGTGAAGACCTACGAGAAACTCACCGAGATCATCCCCAAGTCA
GCCGTGGGGGAGCTGTCTGAGGACTCCAGCAATGTGGTCCATCTCATTAAGAATGCTTAC
AATAAACTCTCCTCCAGGGTCTTCCTGGATCACAACGCCCTCCCCGACACCCTGAAAGTC
ACCTACGACTCCTTCTGCAGCAATGGAGTGACGCACAGGAACCAGCCCAGAGGTGACTGT
GATGGCGTGCAGATCAATGTCCCGATCACCTTCCAGGTGAAGGTCACGGCCACAGAGTGC
ATCCAGGAGCAGTCGTTTGTCATCCGGGCGCTGGGCTTCACGGACATAGTGACCGTGCAG
GTTCTTCCCCAGTGTGAGTGCCGGTGCCGGGACCAGAGCAGAGACCGCAGCCTCTGCCAT
GGCAAGGGCTTCTTGGAGTGCGGCATCTGCAGGTGTGACACTGGCTACATTGGGAAAAAC
TGTGAGTGCCAGACACAGGGCCGGAGCAGCCAGGAGCTGGAAGGAAGCTGCCGGAAGGAC
AACAACTCCATCATCTGCTCAGGGCTGGGGGACTGTGTCTGCGGGCAGTGCCTGTGCCAC
ACCAGCGACGTCCCCGGCAAGCTGATATACGGGCAGTACTGCGAGTGTGACACCATCAAC
TGTGAGCGCTACAACGGCCAGGTCTGCGGCGGCCCGGGGAGGGGGCTCTGCTTCTGCGGG
AAGTGCCGCTGCCACCCGGGCTTTGAGGGCTCAGCGTGCCAGTGCGAGAGGACCACTGAG
GGCTGCCTGAACCCGCGGCGTGTTGAGTGTAGTGGTCGTGGCCGGTGCCGCTGCAACGTA
TGCGAGTGCCATTCAGGCTACCAGCTGCCTCTGTGCCAGGAGTGCCCCGGCTGCCCCTCA
CCCTGTGGCAAGTACATCTCCTGCGCCGAGTGCCTGAAGTTCGAAAAGGGCCCCTTTGGG
AAGAACTGCAGCGCGGCGTGTCCGGGCCTGCAGCTGTCGAACAACCCCGTGAAGGGCAGG
ACCTGCAAGGAGAGGGACTCAGAGGGCTGCTGGGTGGCCTACACGCTGGAGCAGCAGGAC
GGGATGGACCGCTACCTCATCTATGTGGATGAGAGCCGAGAGTGTGTGGCAGGCCCCAAC
ATCGCCGCCATCGTCGGGGGCACCGTGGCAGGCATCGTGCTGATCGGCATTCTCCTGCTG
GTCATCTGGAAGGCTCTGATCCACCTGAGCGACCTCCGGGAGTACAGGCGCTTTGAGAAG
GAGAAGCTCAAGTCCCAGTGGAACAATGATAATCCCCTTTTCAAGAGCGCCACCACGACG
GTCATGAACCCCAAGTTTGCTGAGAGTTAG

1. Bianchi E, Denti S, Granata A, Bossi G, Geginat J, Villa A, Rogge L, Pardi R: Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature. 2000 Apr 6;404(6778):617-21. [PubMed ]
2. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. [PubMed ]
3. Fagerholm S, Morrice N, Gahmberg CG, Cohen P: Phosphorylation of the cytoplasmic domain of the integrin CD18 chain by protein kinase C isoforms in leukocytes. J Biol Chem. 2002 Jan 18;277(3):1728-38. Epub 2001 Nov 7. [PubMed ]
4. Nelson C, Rabb H, Arnaout MA: Genetic cause of leukocyte adhesion molecule deficiency. Abnormal splicing and a missense mutation in a conserved region of CD18 impair cell surface expression of beta 2 integrins. J Biol Chem. 1992 Feb 15;267(5):3351-7. [PubMed ]
5. Back AL, Kwok WW, Hickstein DD: Identification of two molecular defects in a child with leukocyte adherence deficiency. J Biol Chem. 1992 Mar 15;267(8):5482-7. [PubMed ]
6. Corbi AL, Vara A, Ursa A, Garcia Rodriguez MC, Fontan G, Sanchez-Madrid F: Molecular basis for a severe case of leukocyte adhesion deficiency. Eur J Immunol. 1992 Jul;22(7):1877-81. [PubMed ]
7. Matsuura S, Kishi F, Tsukahara M, Nunoi H, Matsuda I, Kobayashi K, Kajii T: Leukocyte adhesion deficiency: identification of novel mutations in two Japanese patients with a severe form. Biochem Biophys Res Commun. 1992 May 15;184(3):1460-7. [PubMed ]
8. Weitzman JB, Wells CE, Wright AH, Clark PA, Law SK: The gene organisation of the human beta 2 integrin subunit (CD18). FEBS Lett. 1991 Dec 2;294(1-2):97-103. [PubMed ]
9. Wardlaw AJ, Hibbs ML, Stacker SA, Springer TA: Distinct mutations in two patients with leukocyte adhesion deficiency and their functional correlates. J Exp Med. 1990 Jul 1;172(1):335-45. [PubMed ]
10. Arnaout MA, Dana N, Gupta SK, Tenen DG, Fathallah DM: Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency. J Clin Invest. 1990 Mar;85(3):977-81. [PubMed ]
11. 2954816 Law SK, Gagnon J, Hildreth JE, Wells CE, Willis AC, Wong AJ: The primary structure of the beta-subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150,95 and its relationship to the fibronectin receptor. EMBO J. 1987 Apr;6(4):915-9.
12. 3028646 Kishimoto TK, O'Connor K, Lee A, Roberts TM, Springer TA: Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681-90.
13. 7686755 Back AL, Kerkering M, Baker D, Bauer TR, Embree LJ, Hickstein DD: A point mutation associated with leukocyte adhesion deficiency type 1 of moderate severity. Biochem Biophys Res Commun. 1993 Jun 30;193(3):912-8.
14. 9884339 Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, Klein N: A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999 Jan;103(1):97-106.

1. Katano H, Pesnicak L, Cohen JI: Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV lymphomas. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4960-5. Epub 2004 Mar 23. [PubMed ]
2. Takahashi HK, Mori S, Iwagaki H, Yoshino T, Tanaka N, Nishibori M: Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells. Clin Immunol. 2005 Sep;116(3):211-6. [PubMed ]
3. Fujii T, Masuyama K, Kawashima K: Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways. J Neuroimmunol. 2006 Oct;179(1-2):101-7. Epub 2006 Jul 10. [PubMed ]
4. Fujii T, Takada-Takatori Y, Kawashima K: Roles played by lymphocyte function-associated antigen-1 in the regulation of lymphocytic cholinergic activity. Life Sci. 2007 May 30;80(24-25):2320-4. Epub 2007 Jan 17. [PubMed ]

1. CCL2
2. HC11
3. MCAF
4. MCP-1
5. Monocyte chemoattractant protein 1
6. Monocyte chemotactic and activating factor
7. Monocyte chemotactic protein 1
8. Monocyte secretory protein JE
9. Small inducible cytokine A2 precursor

MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT

• IL8 (PF00048 )

• 1-23

• None

• Secreted protein

ATGAAAGTCTCTGCCGCCCTTCTGTGCCTGCTGCTCATAGCAGCCACCTTCATTCCCCAA
GGGCTCGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTATAACTTCACCAAT
AGGAAGATCTCAGTGCAGAGGCTCGCGAGCTATAGAAGAATCACCAGCAGCAAGTGTCCC
AAAGAAGCTGTGATCTTCAAGACCATTGTGGCCAAGGAGATCTGTGCTGACCCCAAGCAG
AAGTGGGTTCAGGATTCCATGGACCACCTGGACAAGCAAACCCAAACTCCGAAGACTTGA

1. Finzer P, Soto U, Delius H, Patzelt A, Coy JF, Poustka A, zur Hausen H, Rosl F: Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role of the chromatin structure and AP-1 composition. Oncogene. 2000 Jul 6;19(29):3235-44. [PubMed ]
2. Yoshimura T, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Adv Exp Med Biol. 1991;305:47-56. [PubMed ]
3. Gronenborn AM, Clore GM: Modeling the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 on the basis of the solution structure of interleukin-8. Protein Eng. 1991 Feb;4(3):263-9. [PubMed ]
4. Rollins BJ, Morton CC, Ledbetter DH, Eddy RL Jr, Shows TB: Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines clustered at the same locus. Genomics. 1991 Jun;10(2):489-92. [PubMed ]
5. Decock B, Conings R, Lenaerts JP, Billiau A, Van Damme J: Identification of the monocyte chemotactic protein from human osteosarcoma cells and monocytes: detection of a novel N-terminally processed form. Biochem Biophys Res Commun. 1990 Mar 30;167(3):904-9. [PubMed ]
6. Shyy YJ, Li YS, Kolattukudy PE: Structure of human monocyte chemotactic protein gene and its regulation by TPA. Biochem Biophys Res Commun. 1990 Jun 15;169(2):346-51. [PubMed ]
7. Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ: Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487-93. [PubMed ]
8. Rollins BJ, Stier P, Ernst T, Wong GG: The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687-95. [PubMed ]
9. Chang HC, Hsu F, Freeman GJ, Griffin JD, Reinherz EL: Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family. Int Immunol. 1989;1(4):388-97. [PubMed ]
10. Robinson EA, Yoshimura T, Leonard EJ, Tanaka S, Griffin PR, Shabanowitz J, Hunt DF, Appella E: Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1850-4. [PubMed ]
11. 2923622 Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, Matsushima K: Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249-55.
12. 8107690 Li YS, Shyy YJ, Wright JG, Valente AJ, Cornhill JF, Kolattukudy PE: The expression of monocyte chemotactic protein (MCP-1) in human vascular endothelium in vitro and in vivo. Mol Cell Biochem. 1993 Sep 8;126(1):61-8.
13. 8195247 Zhang YJ, Rutledge BJ, Rollins BJ: Structure/activity analysis of human monocyte chemoattractant protein-1 (MCP-1) by mutagenesis. Identification of a mutated protein that inhibits MCP-1-mediated monocyte chemotaxis. J Biol Chem. 1994 Jun 3;269(22):15918-24.
14. 8627182 Weber M, Uguccioni M, Baggiolini M, Clark-Lewis I, Dahinden CA: Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant. J Exp Med. 1996 Feb 1;183(2):681-5.
15. 8639605 Handel TM, Domaille PJ: Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer. Biochemistry. 1996 May 28;35(21):6569-84.
16. 8898111 Kim KS, Rajarathnam K, Clark-Lewis I, Sykes BD: Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3. FEBS Lett. 1996 Oct 21;395(2-3):277-82.
17. 8989326 Lubkowski J, Bujacz G, Boque L, Domaille PJ, Handel TM, Wlodawer A: The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions. Nat Struct Biol. 1997 Jan;4(1):64-9.

1. Kowalski J, Okopien B, Madej A, Zielinski M, Belowski D, Kalina Z, Herman ZS: Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia. Eur J Clin Pharmacol. 2003 Jul;59(3):189-93. Epub 2003 May 17. [PubMed ]
2. Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME: Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis. 2003 Apr;167(2):187-94. [PubMed ]
3. Koh KK, Son JW, Ahn JY, Jin DK, Kim HS, Kim DS, Han SH, Chung WJ, Park GS, Shin EK: Vascular effects of simvastatin combined with ramipril in hypercholesterolemic patients with coronary artery disease, compared with simvastatin alone: a randomized, double-blind, placebo-controlled, crossover study. Atherosclerosis. 2004 Nov;177(1):147-53. [PubMed ]
4. Han KH, Ryu J, Hong KH, Ko J, Pak YK, Kim JB, Park SW, Kim JJ: HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo. Circulation. 2005 Mar 22;111(11):1439-47. [PubMed ]
5. Veillard NR, Braunersreuther V, Arnaud C, Burger F, Pelli G, Steffens S, Mach F: Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis. 2006 Sep;188(1):51-8. [PubMed ]

1. Angiotensinogen precursor
2. Serpin A8

MRKRAPQSEMAPAGVSLRATILCLLAWAGLAAGDRVYIHPFHLVIHNESTCEQLAKANAG
KPKDPTFIPAPIQAKTSPVDEKALQDQLVLVAAKLDTEDKLRAAMVGMLANFLGFRIYGM
HSELWGVVHGATVLSPTAVFGTLASLYLGALDHTADRLQAILGVPWKDKNCTSRLDAHKV
LSALQAVQGLLVAQGRADSQAQLLLSTVVGVFTAPGLHLKQPFVQGLALYTPVVLPRSLD
FTELDVAAEKIDRFMQAVTGWKTGCSLMGASVDSTLAFNTYVHFQGKMKGFSLLAEPQEF
WVDNSTSVSVPMLSGMGTFQHWSDIQDNFSVTQVPFTESACLLLIQPHYASDLDKVEGLT
FQQNSLNWMKKLSPRTIHLTMPQLVLQGSYDLQDLLAQAELPAILHTELNLQKLSNDRIR
VGEVLNSIFFELEADEREPTESTQQLNKPEVLEVTLNRPFLFAVYDQSATALHFLGRVAN
PLSTA

• Serpin (PF00079 )

• 1-33

• None

• Secreted protein

ATGCGGAAGCGAGCACCCCAGTCTGAGATGGCTCCTGCCGGTGTGAGCCTGAGGGCCACC
ATCCTCTGCCTCCTGGCCTGGGCTGGCCTGGCTGCAGGTGACCGGGTGTACATACACCCC
TTCCACCTCGTCATCCACAATGAGAGTACCTGTGAGCAGCTGGCAAAGGCCAATGCCGGG
AAGCCCAAAGACCCCACCTTCATACCTGCTCCAATTCAGGCCAAGACATCCCCTGTGGAT
GAAAAGGCCCTACAGGACCAGCTGGTGCTAGTCGCTGCAAAACTTGACACCGAAGACAAG
TTGAGGGCCGCAATGGTCGGGATGCTGGCCAACTTCTTGGGCTTCCGTATATATGGCATG
CACAGTGAGCTATGGGGCGTGGTCCATGGGGCCACCGTCCTCTCCCCAACGGCTGTCTTT
GGCACCCTGGCCTCTCTCTATCTGGGAGCCTTGGACCACACAGCTGACAGGCTACAGGCA
ATCCTGGGTGTTCCTTGGAAGGACAAGAACTGCACCTCCCGGCTGGATGCGCACAAGGTC
CTGTCTGCCCTGCAGGCTGTACAGGGCCTGCTAGTGGCCCAGGGCAGGGCTGATAGCCAG
GCCCAGCTGCTGCTGTCCACGGTGGTGGGCGTGTTCACAGCCCCAGGCCTGCACCTGAAG
CAGCCGTTTGTGCAGGGCCTGGCTCTCTATACCCCTGTGGTCCTCCCACGCTCTCTGGAC
TTCACAGAACTGGATGTTGCTGCTGAGAAGATTGACAGGTTCATGCAGGCTGTGACAGGA
TGGAAGACTGGCTGCTCCCTGATGGGAGCCAGTGTGGACAGCACCCTGGCTTTCAACACC
TACGTCCACTTCCAAGGGAAGATGAAGGGCTTCTCCCTGCTGGCCGAGCCCCAGGAGTTC
TGGGTGGACAACAGCACCTCAGTGTCTGTTCCCATGCTCTCTGGCATGGGCACCTTCCAG
CACTGGAGTGACATCCAGGACAACTTCTCGGTGACTCAAGTGCCCTTCACTGAGAGCGCC
TGCCTGCTGCTGATCCAGCCTCACTATGCCTCTGACCTGGACAAGGTGGAGGGTCTCACT
TTCCAGCAAAACTCCCTCAACTGGATGAAGAAACTGTCTCCCCGGACCATCCACCTGACC
ATGCCCCAACTGGTGCTGCAAGGATCTTATGACCTGCAGGACCTGCTCGCCCAGGCTGAG
CTGCCCGCCATTCTGCACACCGAGCTGAACCTGCAAAAATTGAGCAATGACCGCATCAGG
GTGGGGGAGGTGCTGAACAGCATTTTTTTTGAGCTTGAAGCGGATGAGAGAGAGCCCACA
GAGTCTACCCAACAGCTTAACAAGCCTGAGGTCTTGGAGGTGACCCTGAACCGCCCATTC
CTGTTTGCTGTGTATGATCAAAGCGCCACTGCCCTGCACTTCCTGGGCCGCGTGGCCAAC
CCGCTGAGCACAGCATGA

1. Goodfriend TL, Peach MJ: Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. [PubMed ]
2. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, et al.: Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169-80. [PubMed ]
3. Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990 May 5;265(13):7576-82. [PubMed ]
4. Kunapuli SP, Kumar A: Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart. Circ Res. 1987 May;60(5):786-90. [PubMed ]
5. Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99. [PubMed ]
6. Kunapuli SP, Benedict CR, Kumar A: Tissue specific hormonal regulation of the rat angiotensinogen gene expression. Arch Biochem Biophys. 1987 May 1;254(2):642-6. [PubMed ]
7. Campbell DJ, Bouhnik J, Coezy E, Menard J, Corvol P: Processing of rat and human angiotensinogen precursors by microsomal membranes. Mol Cell Endocrinol. 1985 Nov;43(1):31-40. [PubMed ]
8. Arakawa K, Minohara A, Yamada J, Nakamura M: Enzymatic degradation and electrophoresis of human angiotensin I. Biochim Biophys Acta. 1968 Sep 10;168(1):106-12. [PubMed ]
9. Kageyama R, Ohkubo H, Nakanishi S: Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry. 1984 Jul 31;23(16):3603-9. [PubMed ]
10. Tewksbury DA, Dart RA, Travis J: The amino terminal amino acid sequence of human angiotensinogen. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1311-5. [PubMed ]
11. 7539791 Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, Gleich GJ, Sottrup-Jensen L: Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem. 1995 Jun 9;270(23):13645-51.
12. 7607642 Hixson JE, Powers PK: Detection and characterization of new mutations in the human angiotensinogen gene (AGT). Hum Genet. 1995 Jul;96(1):110-2.
13. 7744780 Inoue I, Rohrwasser A, Helin C, Jeunemaitre X, Crain P, Bohlender J, Lifton RP, Corvol P, Ward K, Lalouel JM: A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system. J Biol Chem. 1995 May 12;270(19):11430-6.
14. 8513325 Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, et al.: A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet. 1993 May;4(1):59-61.
15. 8621667 Gimenez-Roqueplo AP, Leconte I, Cohen P, Simon D, Guyene TT, Celerier J, Pau B, Corvol P, Clauser E, Jeunemaitre X: The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein. J Biol Chem. 1996 Apr 19;271(16):9838-44.
16. 9492317 Carpenter KA, Wilkes BC, Schiller PW: The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment. Eur J Biochem. 1998 Jan 15;251(1-2):448-53.

1. Kunieda Y, Nakagawa K, Nishimura H, Kato H, Ukimura N, Yano S, Kawano H, Kimura S, Nakagawa M, Tsuji H: HMG CoA reductase inhibitor suppresses the expression of tissue factor and plasminogen activator inhibitor-1 induced by angiotensin II in cultured rat aortic endothelial cells. Thromb Res. 2003 Jun 1;110(4):227-34. [PubMed ]
2. Zeng L, Xu H, Chew TL, Chisholm R, Sadeghi MM, Kanwar YS, Danesh FR: Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27. J Am Soc Nephrol. 2004 Jul;15(7):1711-20. [PubMed ]
3. Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG, Zucker IH: Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation. 2005 Sep 20;112(12):1763-70. Epub 2005 Sep 12. [PubMed ]
4. Bayorh MA, Ganafa AA, Eatman D, Walton M, Feuerstein GZ: Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension. Am J Hypertens. 2005 Nov;18(11):1496-502. [PubMed ]
5. Banes-Berceli AK, Shaw S, Ma G, Brands M, Eaton DC, Stern DM, Fulton D, Caldwell RW, Marrero MB: Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells. Am J Physiol Renal Physiol. 2006 Jul;291(1):F116-21. Epub 2006 Jan 31. [PubMed ]

1. EC 2.7.11.24
2. ERK-1
3. ERT2
4. Extracellular signal-regulated kinase 1
5. Insulin-stimulated MAP2 kinase
6. MAP kinase 1
7. MAPK 1
8. Microtubule- associated protein 2 kinase
9. p44-ERK1
10. p44-MAPK

MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAY
DHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYI
VQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL
KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLS
NRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSD
SKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL
KELIFQETARFQPGVLEAP

• ATP + a protein = ADP + a phosphoprotein

• Pkinase (PF00069 )

• None

• None

ATGGCGGCGGCGGCGGCTCAGGGGGGCGGGGGCGGGGAGCCCCGTAGAACCGAGGGGGTC
GGCCCGGGGGTCCCGGGGGAGGTGGAGATGGTGAAGGGGCAGCCGTTCGACGTGGGCCCG
CGCTACACGCAGTTGCAGTACATCGGCGAGGGCGCGTACGGCATGGTCAGCTCGGCCTAT
GACCACGTGCGCAAGACTCGCGTGGCCATCAAGAAGATCAGCCCCTTCGAACATCAGACC
TACTGCCAGCGCACGCTCCGGGAGATCCAGATCCTGCTGCGCTTCCGCCATGAGAATGTC
ATCGGCATCCGAGACATTCTGCGGGCGTCCACCCTGGAAGCCATGAGAGATGTCTACATT
GTGCAGGACCTGATGGAGACTGACCTGTACAAGTTGCTGAAAAGCCAGCAGCTGAGCAAT
GACCATATCTGCTACTTCCTCTACCAGATCCTGCGGGGCCTCAAGTACATCCACTCCGCC
AACGTGCTCCACCGAGATCTAAAGCCCTCCAACCTGCTCAGCAACACCACCTGCGACCTT
AAGATTTGTGATTTCGGCCTGGCCCGGATTGCCGATCCTGAGCATGACCACACCGGCTTC
CTGACGGAGTATGTGGCTACGCGCTGGTACCGGGCCCCAGAGATCATGCTGAACTCCAAG
GGCTATACCAAGTCCATCGACATCTGGTCTGTGGGCTGCATTCTGGCTGAGATGCTCTCT
AACCGGCCCATCTTCCCTGGCAAGCACTACCTGGATCAGCTCAACCACATTCTGGGCATC
CTGGGCTCCCCATCCCAGGAGGACCTGAATTGTATCATCAACATGAAGGCCCGAAACTAC
CTACAGTCTCTGCCCTCCAAGACCAAGGTGGCTTGGGCCAAGCTTTTCCCCAAGTCAGAC
TCCAAAGCCCTTGACCTGCTGGACCGGATGTTAACCTTTAACCCCAATAAACGGATCACA
GTGGAGGAAGCGCTGGCTCACCCCTACCTGGAGCAGTACTATGACCCGACGGATGAGCCA
GTGGCCGAGGAGCCCTTCACCTTCGCCATGGAGCTGGATGACCTACCTAAGGAGCGGCTG
AAGGAGCTCATCTTCCAGGAGACAGCACGCTTCCAGCCCGGAGTGCTGGAGGCCCCCTAG

1. Gonzalez FA, Raden DL, Rigby MR, Davis RJ: Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 1992 Jun 15;304(2-3):170-8. [PubMed ]
2. Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD: Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1416-22. [PubMed ]
3. Charest DL, Mordret G, Harder KW, Jirik F, Pelech SL: Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1. Mol Cell Biol. 1993 Aug;13(8):4679-90. [PubMed ]
4. Greenway A, Azad A, Mills J, McPhee D: Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. J Virol. 1996 Oct;70(10):6701-8. [PubMed ]

1. Sironi L, Banfi C, Brioschi M, Gelosa P, Guerrini U, Nobili E, Gianella A, Paoletti R, Tremoli E, Cimino M: Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment. Neurobiol Dis. 2006 May;22(2):445-51. Epub 2006 Feb 9. [PubMed ]
2. Tristano AG, Castejon AM, Castro A, Cubeddu LX: Effects of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 2007 Feb 2;353(1):11-7. Epub 2006 Nov 17. [PubMed ]
3. Ogura T, Tanaka Y, Nakata T, Namikawa T, Kataoka H, Ohtsubo Y: Simvastatin reduces insulin-like growth factor-1 signaling in differentiating C2C12 mouse myoblast cells in an HMG-CoA reductase inhibition-independent manner. J Toxicol Sci. 2007 Feb;32(1):57-67. [PubMed ]
4. Jiang JL, Wang S, Li NS, Zhang XH, Deng HW, Li YJ: The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is mediated by MAPK pathways in endothelial cells. Biochem Cell Biol. 2007 Feb;85(1):66-77. [PubMed ]

1. Fragment

RFLQQDKYECHFFNGTERVRFLHRDIYNQEEDLRFDSDVGEYRAVTELGRPDAEYWNSQK
DILEQARAAVDTYCRHNYGAVESFTVQRR

• MHC_II_beta (PF00969 )

• None

• None

CACGTTTCTTGCAGCAGGATAAGTATGAGTGTCATTTCTTCAACGGGACGGAGCGGGTGC
GGTTCCTGCACAGAGACATCTATAACCAAGAGGAGGACTTGCGCTTCGACAGCGACGTGG
GGGAGTACCGGGCGGTGACGGAGCTGGGGCGGCCTGACGCTGAGTACTGGAACAGCCAGA
AGGACATCCTGGAGCAGGCGCGGGCCGCGGTGGACACCTACTGCAGACACAACTACGGGG
CTGTGGAGAGCTTCACAGTGCAGCGGCGA

1. Kervaire B, Tiercy JM: Sequence of a new HLA-DR allele, DRB5*0106. Eur J Immunogenet. 1997 Jun;24(3):225-8. [PubMed ]

1. Cherfan P, Tompa A, Wikby A, Lofgren S, Jonasson L: Effects of simvastatin on human T cells in vivo. Atherosclerosis. 2007 Jul;193(1):186-92. Epub 2006 Jul 24. [PubMed ]
2. Ghittoni R, Napolitani G, Benati D, Ulivieri C, Patrussi L, Laghi Pasini F, Lanzavecchia A, Baldari CT: Simvastatin inhibits the MHC class II pathway of antigen presentation by impairing Ras superfamily GTPases. Eur J Immunol. 2006 Nov;36(11):2885-93. [PubMed ]
3. Mahmoud KM, Sobh MA, El-Shenawy F, Isamil AM, El-Magd MA, Hassan NA, El-Agroudy AE, Sheashaa HA, Opelz G, Ghoneim MA: Can intravenous immunoglobulin and simvastatin solve the problem of sensitization in renal transplant candidates? Int Urol Nephrol. 2007;39(3):979-81. Epub 2007 May 31. [PubMed ]

1. CD54 antigen
2. ICAM-1
3. Intercellular adhesion molecule 1 precursor
4. Major group rhinovirus receptor

MAPSSPRPALPALLVLLGALFPGPGNAQTSVSPSKVILPRGGSVLVTCSTSCDQPKLLGI
ETPLPKKELLLPGNNRKVYELSNVQEDSQPMCYSNCPDGQSTAKTFLTVYWTPERVELAP
LPSWQPVGKNLTLRCQVEGGAPRANLTVVLLRGEKELKREPAVGEPAEVTTTVLVRRDHH
GANFSCRTELDLRPQGLELFENTSAPYQLQTFVLPATPPQLVSPRVLEVDTQGTVVCSLD
GLFPVSEAQVHLALGDQRLNPTVTYGNDSFSAKASVSVTAEDEGTQRLTCAVILGNQSQE
TLQTVTIYSFPAPNVILTKPEVSEGTEVTVKCEAHPRAKVTLNGVPAQPLGPRAQLLLKA
TPEDNGRSFSCSATLEVAGQLIHKNQTRELRVLYGPRLDERDCPGNWTWPENSQQTPMCQ
AWGNPLPELKCLKDGTFPLPIGESVTVTRDLEGTYLCRARSTQGEVTRKVTVNVLSPRYE
IVIITVVAAAVIMGTAGLSTYLYNRQRKIKKYRLQQAQKGTPMKPNTQATPP

• ICAM_N (PF03921 )

• 1-27

• 481-503

• Membrane
• single-pass type I membrane protein

ATGGCTCCCAGCAGCCCCCGGCCCGCGCTGCCCGCACTCCTGGTCCTGCTCGGGGCTCTG
TTCCCAGGACCTGGCAATGCCCAGACATCTGTGTCCCCCTCAAAAGTCATCCTGCCCCGG
GGAGGCTCCGTGCTGGTGACATGCAGCACCTCCTGTGACCAGCCCAAGTTGTTGGGCATA
GAGACCCCGTTGCCTAAAAAGGAGTTGCTCCTGCCTGGGAACAACCGGAAGGTGTATGAA
CTGAGCAATGTGCAAGAAGATAGCCAACCAATGTGCTATTCAAACTGCCCTGATGGGCAG
TCAACAGCTAAAACCTTCCTCACCGTGTACTGGACTCCAGAACGGGTGGAACTGGCACCC
CTCCCCTCTTGGCAGCCAGTGGGCAAGAACCTTACCCTACGCTGCCAGGTGGAGGGTGGG
GCACCCCGGGCCAACCTCACCGTGGTGCTGCTCCGTGGGGAGAAGGAGCTGAAACGGGAG
CCAGCTGTGGGGGAGCCCGCTGAGGTCACGACCACGGTGCTGGTGAGGAGAGATCACCAT
GGAGCCAATTTCTCGTGCCGCACTGAACTGGACCTGCGGCCCCAAGGGCTGGAGCTGTTT
GAGAACACCTCGGCCCCCTACCAGCTCCAGACCTTTGTCCTGCCAGCGACTCCCCCACAA
CTTGTCAGCCCCCGGGTCCTAGAGGTGGACACGCAGGGGACCGTGGTCTGTTCCCTGGAC
GGGCTGTTCCCAGTCTCGGAGGCCCAGGTCCACCTGGCACTGGGGGACCAGAGGTTGAAC
CCCACAGTCACCTATGGCAACGACTCCTTCTCGGCCAAGGCCTCAGTCAGTGTGACCGCA
GAGGACGAGGGCACCCAGCGGCTGACGTGTGCAGTAATACTGGGGAACCAGAGCCAGGAG
ACACTGCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGTGATTCTGACGAAGCCA
GAGGTCTCAGAAGGGACCGAGGTGACAGTGAAGTGTGAGGCCCACCCTAGAGCCAAGGTG
ACGCTGAATGGGGTTCCAGCCCAGCCACTGGGCCCGAGGGCCCAGCTCCTGCTGAAGGCC
ACCCCAGAGGACAACGGGCGCAGCTTCTCCTGCTCTGCAACCCTGGAGGTGGCCGGCCAG
CTTATACACAAGAACCAGACCCGGGAGCTTCGTGTCCTGTATGGCCCCCGACTGGACGAG
AGGGATTGTCCGGGAAACTGGACGTGGCCAGAAAATTCCCAGCAGACTCCAATGTGCCAG
GCTTGGGGGAACCCATTGCCCGAGCTCAAGTGTCTAAAGGATGGCACTTTCCCACTGCCC
ATCGGGGAATCAGTGACTGTCACTCGAGATCTTGAGGGCACCTACCTCTGTCGGGCCAGG
AGCACTCAAGGGGAGGTCACCCGCGAGGTGACCGTGAATGTGCTCTCCCCCCGGTATGAG
ATTGTCATCATCACTGTGGTAGCAGCCGCAGTCATAATGGGCACTGCAGGCCTCAGCACG
TACCTCTATAACCGCCAGCGGAAGATCAAGAAATACAGACTACAACAGGCCCAAAAAGGG
ACCCCCATGAAACCGAACACACAAGCCACGCCTCCCTGA

1. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed ]
2. Kolatkar PR, Bella J, Olson NH, Bator CM, Baker TS, Rossmann MG: Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. EMBO J. 1999 Nov 15;18(22):6249-59. [PubMed ]
3. Voraberger G, Schafer R, Stratowa C: Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester. J Immunol. 1991 Oct 15;147(8):2777-86. [PubMed ]
4. Stade BG, Messer G, Riethmuller G, Johnson JP: Structural characteristics of the 5' region of the human ICAM-1 gene. Immunobiology. 1990 Dec;182(1):79-87. [PubMed ]
5. Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A: The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839-47. [PubMed ]
6. Tomassini JE, Graham D, DeWitt CM, Lineberger DW, Rodkey JA, Colonno RJ: cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4907-11. [PubMed ]
7. Simmons D, Makgoba MW, Seed B: ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624-7. [PubMed ]
8. Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA: Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988 Mar 25;52(6):925-33. [PubMed ]
9. Vora DK, Rosenbloom CL, Beaudet AL, Cottingham RW: Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics. 1994 Jun;21(3):473-7. [PubMed ]
10. Wenzel K, Ernst M, Rohde K, Baumann G, Speer A: DNA polymorphisms in adhesion molecule genes--a new risk factor for early atherosclerosis. Hum Genet. 1996 Jan;97(1):15-20. [PubMed ]
11. 9259284 Fernandez-Reyes D, Craig AG, Kyes SA, Peshu N, Snow RW, Berendt AR, Marsh K, Newbold CI: A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet. 1997 Aug;6(8):1357-60.
12. 9539702 Casasnovas JM, Stehle T, Liu JH, Wang JH, Springer TA: A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4134-9.
13. 9539703 Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG: The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4140-5.

1. Sbarouni E, Flevari P, Kroupis C, Kyriakides ZS, Koniavitou K, Kremastinos DT: The effects of raloxifene and simvastatin on plasma lipids and endothelium. Cardiovasc Drugs Ther. 2003 Jul;17(4):319-23. [PubMed ]
2. Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D: Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004 Mar;53(3):701-10. [PubMed ]
3. Lopes-Virella MF, Mironova M, Stephan E, Durazo-Arvizu R, Virella G: Role of simvastatin as an immunomodulator in type 2 diabetes. Diabetes Care. 2004 Apr;27(4):908-13. [PubMed ]
4. Miyahara S, Kiryu J, Yamashiro K, Miyamoto K, Hirose F, Tamura H, Katsuta H, Nishijima K, Tsujikawa A, Honda Y: Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes. Am J Pathol. 2004 May;164(5):1697-706. [PubMed ]
5. Zapolska-Downar D, Siennicka A, Kaczmarczyk M, Kolodziej B, Naruszewicz M: Simvastatin modulates TNFalpha-induced adhesion molecules expression in human endothelial cells. Life Sci. 2004 Jul 30;75(11):1287-302. [PubMed ]

1. Cell migration-inducing gene 5 protein
2. Ras- like protein TC25
3. Ras-related C3 botulinum toxin substrate 1 precursor
4. p21-Rac1

MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAG
QEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR
DDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPP
PVKKRKRKCLLL

• Ras (PF00071 )

• None

• None

• Cell membrane
• cytoplasmic side. Melanosome. Note=Inner surface of plasma membrane pos
• lipid-anchor

ATGCAGGCCATCAAGTGTGTGGTGGTGGGAGACGGAGCTGTAGGTAAAACTTGCCTACTG
ATCAGTTACACAACCAATGCATTTCCTGGAGAATATATCCCTACTGTCTTTGACAATTAT
TCTGCCAATGTTATGGTAGATGGAAAACCGGTGAATCTGGGCTTATGGGATACAGCTGGA
CAAGAAGATTATGACAGATTACGCCCCCTATCCTATCCGCAAACAGATGTGTTCTTAATT
TGCTTTTCCCTTGTGAGTCCTGCATCATTTGAAAATGTCCGTGCAAAGTGGTATCCTGAG
GTGCGGCACCACTGTCCCAACACTCCCATCATCCTAGTGGGAACTAAACTTGATCTTAGG
GATGATAAAGACACGATCGAGAAACTGAAGGAGAAGAAGCTGACTCCCATCACCTATCCG
CAGGGTCTAGCCATGGCTAAGGAGATTGGTGCTGTAAAATACCTGGAGTGCTCGGCGCTC
ACACAGCGAGGCCTCAAGACAGTGTTTGACGAAGCGATCCGAGCAGTCCTCTGCCCGCCT
CCCGTGAAGAAGAGGAAGAGAAAATGCCTGCTGTTGTAA

1. Nishihara H, Kobayashi S, Hashimoto Y, Ohba F, Mochizuki N, Kurata T, Nagashima K, Matsuda M: Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim Biophys Acta. 1999 Nov 11;1452(2):179-87. [PubMed ]
2. Jordan P, Brazao R, Boavida MG, Gespach C, Chastre E: Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene. 1999 Nov 18;18(48):6835-9. [PubMed ]
3. Johansson A, Driessens M, Aspenstrom P: The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J Cell Sci. 2000 Sep;113 ( Pt 18):3267-75. [PubMed ]
4. Vikis HG, Li W, He Z, Guan KL: The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12457-62. [PubMed ]
5. Matos P, Skaug J, Marques B, Beck S, Verissimo F, Gespach C, Boavida MG, Scherer SW, Jordan P: Small GTPase Rac1: structure, localization, and expression of the human gene. Biochem Biophys Res Commun. 2000 Nov 2;277(3):741-51. [PubMed ]
6. Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K: Structure of the TPR domain of p67phox in complex with Rac.GTP. Mol Cell. 2000 Oct;6(4):899-907. [PubMed ]
7. Worthylake DK, Rossman KL, Sondek J: Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature. 2000 Dec 7;408(6813):682-8. [PubMed ]
8. Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A: How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol. 2001 Jan;8(1):23-6. [PubMed ]
9. Stebbins CE, Galan JE: Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell. 2000 Dec;6(6):1449-60. [PubMed ]
10. Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H: Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. Genes Cells. 2001 Feb;6(2):107-19. [PubMed ]
11. 11346801 Tarricone C, Xiao B, Justin N, Walker PA, Rittinger K, Gamblin SJ, Smerdon SJ: The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways. Nature. 2001 May 10;411(6834):215-9.
12. 11513578 Grizot S, Faure J, Fieschi F, Vignais PV, Dagher MC, Pebay-Peyroula E: Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation. Biochemistry. 2001 Aug 28;40(34):10007-13.
13. 11955434 Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, Stephens LR: P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell. 2002 Mar 22;108(6):809-21.
14. 12134158 Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS: Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol. 2002 Aug;4(8):574-82.
15. 12853948 Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64.
16. 1903399 Kinsella BT, Erdman RA, Maltese WA: Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA. J Biol Chem. 1991 May 25;266(15):9786-94.
17. 2108320 Drivas GT, Shih A, Coutavas E, Rush MG, D'Eustachio P: Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990 Apr;10(4):1793-8.
18. 2674130 Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R: rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem. 1989 Oct 5;264(28):16378-82.
19. 7673236 Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G, Camonis JH: Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7.
20. 9033596 Hirshberg M, Stockley RW, Dodson G, Webb MR: The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat Struct Biol. 1997 Feb;4(2):147-52.

1. Negre-Aminou P, van Leeuwen RE, van Thiel GC, van den IJssel P, de Jong WW, Quinlan RA, Cohen LH: Differential effect of simvastatin on activation of Rac(1) vs. activation of the heat shock protein 27-mediated pathway upon oxidative stress, in human smooth muscle cells. Biochem Pharmacol. 2002 Nov 15;64(10):1483-91. [PubMed ]
2. Li JJ, Chen MZ, Chen X, Fang CH: Rapid effects of simvastatin on lipid profile and C-reactive protein in patients with hypercholesterolemia. Clin Cardiol. 2003 Oct;26(10):472-6. [PubMed ]
3. Zeng L, Xu H, Chew TL, Chisholm R, Sadeghi MM, Kanwar YS, Danesh FR: Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27. J Am Soc Nephrol. 2004 Jul;15(7):1711-20. [PubMed ]
4. Ferri N, Colombo G, Ferrandi C, Raines EW, Levkau B, Corsini A: Simvastatin reduces MMP1 expression in human smooth muscle cells cultured on polymerized collagen by inhibiting Rac1 activation. Arterioscler Thromb Vasc Biol. 2007 May;27(5):1043-9. Epub 2007 Feb 15. [PubMed ]
5. Marino F, Guasti L, Cosentino M, Ferrari M, Rasini E, Maio RC, Cimpanelli MG, Cereda E, Crespi C, Simoni C, Restelli D, Venco A, Lecchini S: Angiotensin II type 1 receptor expression in polymorphonuclear leukocytes from high-risk subjects: changes after treatment with simvastatin. J Cardiovasc Pharmacol. 2007 May;49(5):299-305. [PubMed ]

1. COLXIIIA1
2. XIII

MVAERTHKAAATGARGPGELGAPGTVALVAARAERGARLPSPGSCGLLTLALCSLALSLL
AHFRTAELQARVLRLEAERGEQQMETAILGRVNQLLDEKWKLHSRRRREAPKTSPGCNCP
PGPPGPTGRPGLPGDKGAIGMPGRVGSPGDAGLSIIGPRGPPGQPGTRGFPGFPGPIGLD
GKPGHPGPKGDMGLTGPPGQPGPQGQKGEKGQCGEYPHRECLSSMPAALRSSQIIALKLL
PLLNSVRLAPPPVIKRRTFQGEQSQASIQGPPGPPGPPGPSGPLGHPGLPGPMGPPGLPG
PPGPKGDPGIQGYHGRKGERGMPGMPGKHGAKGAPGIAVAGMKGEPGIPGTKGEKGAEGS
PGLPGLLGQKGEKGDAGNSIGGGRGEPGPPGLPGPPGPKGEAGVDGQVGPPGQPGDKGER
GAAGEQGPDGPKGSKGEPGKGEMVDYNGNINEALQEIRTLALMGPPGLPGQIGPPGAPGI
PGQKGEIGLPGPPGHDGEKGPRGKPGDMGPPGPQGPPGKDGPPGVKGENGHPGSPGEKGE
KGETGQAGSPGEKGEAGEKGNPGAEVPGLPGPEGPPGPPGLQGVPGPKGEAGLDGAKGEK
GFQGEKGDRGPLGLPGASGLDGRPGPPGTPGPIGVPGPAGPKGERGSKGDPGMTGPTGAA
GLPGLHGPPGDKGNRGERGKKGSRGPKGDKGDQGAPGLDAPCPLGEDGLPVQGCWNK

• Collagen (PF01391 )

• None

• 45-61

• Cell membrane
• single-pass type II membrane protein

ATGGTAGCGGAGCGCACCCACAAAGCGGCAGCCACCGGTGCCCGCGGCCCTGGGGAGTTG
GGCGCGCCCGGGACGGTGGCTCTGGTGGCGGCGCGGGCGGAGCGCGGCGCACGGCTGCCG
AGTCCAGGGTCGTGCGGGCTGCTGACGCTGGCCCTCTGCTCGCTGGCACTCAGCCTGCTC
GCCCACTTTCGGACGGCCGAGCTGCAGGCCCGGGTGCTGCGCCTGGAAGCGGAGCGCGGG
GAGCAGCAAATGGAGACAGCTATTTTGGGACGAGTCAATCAACTGCTGGACGAGAAATGG
AAGCTCCACTCAAGGAGGCGCCGGGAGGCCCCAAAGACATCTCCAGGATGTAACTGCCCA
CCAGGACCTCCTGGTCCCACTGGAAGACCCGGACTCCCAGGGGACAAAGGTGCCATTGGG
ATGCCTGGACGTGTGGGGTCCCCCGGAGACGCTGGGCTGTCCATCATTGGTCCCCGCGGC
CCCCCTGGTCAACCAGGCACTAGAGGTTTCCCTGGATTTCCGGGTCCCATTGGGCTGGAC
GGCAAACCGGGCCACCCAGGACCAAAGGGCGACATGGGTCTGACGGGTCCCCCAGGACAG
CCGGGACCCCAGGGACAAAAAGGAGAAAAGGGTCAGTGTGGAGAGTACCCACACCGGGAG
TGCCTAAGCAGCATGCCAGCAGCTCTGCGCTCCAGCCAGATAATTGCCCTGAAGCTGCTG
CCTCTCCTCAATTCAGTGCGACTGGCTCCACCCCCGGTCATAAAAAGGCGGACATTCCAG
GGCGAACAGAGCCAGGCCAGCATCCAAGGTCCACCAGGGCCCCCAGGCCCCCCTGGACCA
AGTGGACCTCTGGGGCACCCAGGACTGCCAGGGCCTATGGGGCCACCTGGCTTACCTGGG
CCTCCTGGACCAAAGGGAGACCCAGGGATCCAGGGCTACCACGGCCGGAAGGGAGAACGG
GGCATGCCAGGGATGCCAGGCAAGCATGGAGCCAAGGGGGCGCCCGGAATTGCCGTGGCT
GGGATGAAGGGTGAGCCAGGGATCCCAGGAACCAAGGGTGAGAAGGGGGCTGAAGGCTCC
CCTGGGCTTCCTGGCCTCCTGGGGCAGAAGGGAGAGAAAGGCGATGCTGGCAACTCCATT
GGAGGAGGCAGAGGGGAACCTGGCCCTCCAGGGCTCCCTGCGCCCCCAGGGCCAAAGGGA
GAAGCAGGTGTCGATGGCCAGGTTGGCCCCCCAGGGCAGCCAGGAGACAAGGGGGAGCGT
GGAGCAGCTGGAGAACAGGGACCAGATGGCCCCAAGGGCTCCAAGGGAGAACCAGGGAAA
GGAGAGATGGTGGATTACAATGGAAACATCAATGAGGCTCTCCAGGAGATCCGGACGCTG
GCCTTGATGGGGCCTCCTGGTCTTCCTGGGCAAATTGGCCCACCTGGAGCTCCAGGGATT
CCAGGCCAGAAGGGGGAGATTGGACTGCCAGGCCCTCCAGGACACGATGGGGAAAAGGGA
CCTCGCGGTAAACCAGGAGACATGGGCCCTCCTGGTCCCCAAGGCCCCCCAGGAAAGGAT
GGACCTCCAGGAGTGAAGGGAGAAAACGGGCACCCAGGGAGCCCAGGAGAGAAGGGGGAA
AAAGGGGAGACAGGACAAGCAGGCTCACCGGGAGAGAAAGGAGAAGCCGGGGAGAAGGGC
AATCCAGGAGCAGAGGTTCCTGGGCTGCCAGGGCCAGAGGGGCCTCCCGGACCTCCGGGG
CTCCAAGGTGTTCCTGGACCAAAGGGGGAAGCAGGACTAGATGGAGCAAAAGGAGAGAAA
GGCTTCCAGGGAGAAAAAGGAGACCGTGGTCCCCTGGGACTACCCGGAGCTTCAGGTTTG
GACGGCAGGCCTGGGCCACCGGGTACTCCAGGACCAATTGGAGTTCCAGGCCCAGCGGGA
CCAAAGGGCGAGAGGGGCAGCAAAGGAGACCCTGGGATGACAGGACCAACGGGAGCAGCT
GGGCTTCCTGGTTTACATGGACCACCCGGGGACAAGGGAAACCGGGGGGAGAGGGGGAAG
AAAGGCTCTAGAGGGCCTAAAGGGGACAAGGGAGACCAAGGAGCGCCTGGATTAGATGCC
CCCTGCCCATTGGGCGAAGATGGCTTACCAGTCCAAGGCTGCTGGAACAAGTGA

1. Pihlajaniemi T, Tamminen M: The alpha 1 chain of type XIII collagen consists of three collagenous and four noncollagenous domains, and its primary transcript undergoes complex alternative splicing. J Biol Chem. 1990 Oct 5;265(28):16922-8. [PubMed ]
2. Tikka L, Pihlajaniemi T, Henttu P, Prockop DJ, Tryggvason K: Gene structure for the alpha 1 chain of a human short-chain collagen (type XIII) with alternatively spliced transcripts and translation termination codon at the 5' end of the last exon. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7491-5. [PubMed ]
3. Pihlajaniemi T, Myllyla R, Seyer J, Kurkinen M, Prockop DJ: Partial characterization of a low molecular weight human collagen that undergoes alternative splicing. Proc Natl Acad Sci U S A. 1987 Feb;84(4):940-4. [PubMed ]

1. Cipollone F, Fazia M, Iezzi A, Zucchelli M, Pini B, De Cesare D, Ucchino S, Spigonardo F, Bajocchi G, Bei R, Muraro R, Artese L, Piattelli A, Chiarelli F, Cuccurullo F, Mezzetti A: Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans. Circulation. 2003 Mar 25;107(11):1479-85. [PubMed ]
2. Rombouts K, Kisanga E, Hellemans K, Wielant A, Schuppan D, Geerts A: Effect of HMG-CoA reductase inhibitors on proliferation and protein synthesis by rat hepatic stellate cells. J Hepatol. 2003 May;38(5):564-72. [PubMed ]
3. Maeda T, Matsunuma A, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N: Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem. 2004 Jun 1;92(3):458-71. [PubMed ]
4. Grodzinska L, Starzyk D, Bieron K, Goszcz A, Korbut R: Simvastatin effects in normo- and hypercholesterolaemic patients with peripheral arterial occlusive disease: a pilot study. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):413-9. [PubMed ]
5. Buttice G, Miller J, Wang L, Smith BD: Interferon-gamma induces major histocompatibility class II transactivator (CIITA), which mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells. Circ Res. 2006 Mar 3;98(4):472-9. Epub 2006 Jan 26. [PubMed ]

1. EC 3.4.24.17
2. MMP-3
3. Matrix metalloproteinase-3
4. SL-1
5. Stromelysin-1 precursor
6. Transin-1

MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPV
VKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVN
YTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNV
LAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLY
HSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFDAVS
TLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKGNQF
WAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNSMEP
GFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC

• Preferential cleavage where P1', P2' and P3' are hydrophobic residues

• Hemopexin (PF00045 )
• Peptidase_M10 (PF00413 )
• PG_binding_1 (PF01471 )

• 1-17

• None

• Cytoplasmic

ATGAAGAGTCTTCCAATCCTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATTG
GATGGAGCTGCAAGGGGTGAGGACACCAGCATGAACCTTGTTCAGAAATATCTAGAAAAC
TACTACGACCTCAAAAAAGATGTGAAACAGTTTGTTAGGAGAAAGGACAGTGGTCCTGTT
GTTAAAAAAATCCGAGAAATGCAGAAGTTCCTTGGATTGGAGGTGACGGGGAAGCTGGAC
TCCGACACTCTGGAGGTGATGCGCAAGCCCAGGTGTGGAGTTCCTGATGTTGGTCACTTC
AGAACCTTTCCTGGCATCCCGAAGTGGAGGAAAACCCACCTTACATACAGGATTGTGAAT
TATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCTGTTGAGAAAGCTCTGAAAGTC
TGGGAAGAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGAGGCTGATATAATG
ATCTCTTTTGCAGTTAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAAATGTT
TTGGCCCATGCCTATGCCCCTGGGCCAGGGATTAATGGAGATGCCCACTTTGATGATGAT
GAACAATGGACAAAGGATACAACAGGGACCAATTTATTTCTCGTTGCTGCTCATGAAATT
GGCCACTCCCTGGGTCTCTTTCACTCAGCCAACACTGAAGCTTTGATGTACCCACTCTAT
CACTCACTCACAGACCTGACTCGGTTCCGCCTGTCTCAAGATGATATAAATGGCATTCAG
TCCCTCTATGGACCTCCCCCTGACTCCCCTGAGACCCCCCTGGTACCCACGGAACCTGTC
CCTCCAGAACCTGGGACGCCAGCCAACTGTGATCCTGCTTTGTCCTTTGATGCTGTCAGC
ACTCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTTGGCGCAAATCCCTCAGG
AAGCTTGAACCTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCTTCAGGCGTG
GATGCCGCATATGAAGTTACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATTC
TGGGCCATCAGAGGAAATGAGGTACGAGCTGGATACCCAAGAGGCATCCACACCCTAGGT
TTCCCTCCAACCGTGAGGAAAATCGATGCAGCCATTTCTGATAAGGAAAAGAACAAAACA
TATTTCTTTGTAGAGGACAAATACTGGAGATTTGATGAGAAGAGAAATTCCATGGAGCCA
GGCTTTCCCAAGCAAATAGCTGAAGACTTTCCAGGGATTGACTCAAAGATTGATGCTGTT
TTTGAAGAATTTGGGTTCTTTTATTTCTTTACTGGATCTTCACAGTTGGAGTTTGACCCA
AATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGCTGGCTTAATTGTTGA

1. Pavlovsky AG, Williams MG, Ye QZ, Ortwine DF, Purchase CF 2nd, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D, Humblet C, Blundell TL: X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity. Protein Sci. 1999 Jul;8(7):1455-62. [PubMed ]
2. Chen L, Rydel TJ, Gu F, Dunaway CM, Pikul S, Dunham KM, Barnett BL: Crystal structure of the stromelysin catalytic domain at 2.0 A resolution: inhibitor-induced conformational changes. J Mol Biol. 1999 Oct 29;293(3):545-57. [PubMed ]
3. Nagase H, Enghild JJ, Suzuki K, Salvesen G: Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry. 1990 Jun 19;29(24):5783-9. [PubMed ]
4. Whitham SE, Murphy G, Angel P, Rahmsdorf HJ, Smith BJ, Lyons A, Harris TJ, Reynolds JJ, Herrlich P, Docherty AJ: Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J. 1986 Dec 15;240(3):913-6. [PubMed ]
5. Saus J, Quinones S, Otani Y, Nagase H, Harris ED Jr, Kurkinen M: The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin. J Biol Chem. 1988 May 15;263(14):6742-5. [PubMed ]
6. Wilhelm SM, Collier IE, Kronberger A, Eisen AZ, Marmer BL, Grant GA, Bauer EA, Goldberg GI: Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6725-9. [PubMed ]
7. Gooley PR, O'Connell JF, Marcy AI, Cuca GC, Salowe SP, Bush BL, Hermes JD, Esser CK, Hagmann WK, Springer JP, et al.: The NMR structure of the inhibited catalytic domain of human stromelysin-1. Nat Struct Biol. 1994 Feb;1(2):111-8. [PubMed ]
8. Becker JW, Marcy AI, Rokosz LL, Axel MG, Burbaum JJ, Fitzgerald PM, Cameron PM, Esser CK, Hagmann WK, Hermes JD, et al.: Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme. Protein Sci. 1995 Oct;4(10):1966-76. [PubMed ]
9. Dhanaraj V, Ye QZ, Johnson LL, Hupe DJ, Ortwine DF, Dunbar JB Jr, Rubin JR, Pavlovsky A, Humblet C, Blundell TL: X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily. Structure. 1996 Apr 15;4(4):375-86. [PubMed ]
10. Esser CK, Bugianesi RL, Caldwell CG, Chapman KT, Durette PL, Girotra NN, Kopka IE, Lanza TJ, Levorse DA, MacCoss M, Owens KA, Ponpipom MM, Simeone JP, Harrison RK, Niedzwiecki L, Becker JW, Marcy AI, Axel MG, Christen AJ, McDonnell J, Moore VL, Olszewski JM, Saphos C, Visco DM, Hagmann WK, et al.: Inhibition of stromelysin-1 (MMP-3) by P1'-biphenylylethyl carboxyalkyl dipeptides. J Med Chem. 1997 Mar 14;40(6):1026-40. [PubMed ]
11. 9288970 Gomis-Ruth FX, Maskos K, Betz M, Bergner A, Huber R, Suzuki K, Yoshida N, Nagase H, Brew K, Bourenkov GP, Bartunik H, Bode W: Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature. 1997 Sep 4;389(6646):77-81.
12. 9760240 Li YC, Zhang X, Melton R, Ganu V, Gonnella NC: Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor. Biochemistry. 1998 Oct 6;37(40):14048-56.
13. 9792098 Finzel BC, Baldwin ET, Bryant GL Jr, Hess GF, Wilks JW, Trepod CM, Mott JE, Marshall VP, Petzold GL, Poorman RA, O'Sullivan TJ, Schostarez HJ, Mitchell MA: Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity. Protein Sci. 1998 Oct;7(10):2118-26.
14. 9827994 Stockman BJ, Waldon DJ, Gates JA, Scahill TA, Kloosterman DA, Mizsak SA, Jacobsen EJ, Belonga KL, Mitchell MA, Mao B, Petke JD, Goodman L, Powers EA, Ledbetter SR, Kaytes PS, Vogeli G, Marshall VP, Petzold GL, Poorman RA: Solution structures of stromelysin complexed to thiadiazole inhibitors. Protein Sci. 1998 Nov;7(11):2281-6.

1. Lazzerini PE, Capecchi PL, Nerucci F, Fioravanti A, Chellini F, Piccini M, Bisogno S, Marcolongo R, Laghi Pasini F: Simvastatin reduces MMP-3 level in interleukin 1beta stimulated human chondrocyte culture. Ann Rheum Dis. 2004 Jul;63(7):867-9. [PubMed ]
2. Huang CY, Wu TC, Lin WT, Leu HB, Lin CP, Lin SJ, Chen JW: Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients. Eur J Clin Invest. 2006 Feb;36(2):76-84. [PubMed ]

1. Apopain
2. CASP-3
3. CPP-32
4. Caspase-3 precursor
5. Cysteine protease CPP32
6. EC 3.4.22.56
7. SCA-1
8. SREBP cleavage activity 1
9. Yama protein

MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH

• Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp! with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position

• Peptidase_C14 (PF00656 )

• None

• None

• Cytoplasm

ATGGAGAACACTGAAAACTCAGTGGATTCAAAATCCATTAAAAATTTGGAACCAAAGATC
ATACATGGAAGCGAATCAATGGACTCTGGAATATCCCTGGACAACAGTTATAAAATGGAT
TATCCTGAGATGGGTTTATGTATAATAATTAATAATAAGAATTTTCATAAAAGCACTGGA
ATGACATCTCGGTCTGGTACAGATGTCGATGCAGCAAACCTCAGGGAAACATTCAGAAAC
TTGAAATATGAAGTCAGGAATAAAAATGATCTTACACGTGAAGAAATTGTGGAATTGATG
CGTGATGTTTCTAAAGAAGATCACAGCAAAAGGAGCAGTTTTGTTTGTGTGCTTCTGAGC
CATGGTGAAGAAGGAATAATTTTTGGAACAAATGGACCTGTTGACCTGAAAAAAATAACA
AACTTTTTCAGAGGGGATCGTTGTAGAAGTCTAACTGGAAAACCCAAACTTTTCATTATT
CAGGCCTGCCGTGGTACAGAACTGGACTGTGGCATTGAGACAGACAGTGGTGTTGATGAT
GACATGGCGTGTCATAAAATACCAGTGGATGCCGACTTCTTGTATGCATACTCCACAGCA
CCTGGTTATTATTCTTGGCGAAATTCAAAGGATGGCTCCTGGTTCATCCAGTCGCTTTGT
GCCATGCTGAAACAGTATGCCGACAAGCTTGAATTTATGCACATTCTTACCCGGGTTAAC
CGAAAGGTGGCAACAGAATTTGAGTCCTTTTCCTTTGACGCTACTTTTCATGCAAAGAAA
CAGATTCCATGTATTGTTTCCATGCTCACAAAAGAACTCTATTTTTATCACTAA

1. Lee D, Long SA, Adams JL, Chan G, Vaidya KS, Francis TA, Kikly K, Winkler JD, Sung CM, Debouck C, Richardson S, Levy MA, DeWolf WE Jr, Keller PM, Tomaszek T, Head MS, Ryan MD, Haltiwanger RC, Liang PH, Janson CA, McDevitt PJ, Johanson K, Concha NO, Chan W, Abdel-Meguid SS, Badger AM, Lark MW, Nadeau DP, Suva LJ, Gowen M, Nuttall ME: Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. J Biol Chem. 2000 May 26;275(21):16007-14. [PubMed ]
2. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.: Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. [PubMed ]
3. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM: Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801-9. [PubMed ]
4. Fernandes-Alnemri T, Litwack G, Alnemri ES: CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 1994 Dec 9;269(49):30761-4. [PubMed ]
5. Rotonda J, Nicholson DW, Fazil KM, Gallant M, Gareau Y, Labelle M, Peterson EP, Rasper DM, Ruel R, Vaillancourt JP, Thornberry NA, Becker JW: The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat Struct Biol. 1996 Jul;3(7):619-25. [PubMed ]
6. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR: Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442-9. [PubMed ]
7. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES: In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9. [PubMed ]
8. Mittl PR, Di Marco S, Krebs JF, Bai X, Karanewsky DS, Priestle JP, Tomaselli KJ, Grutter MG: Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone. J Biol Chem. 1997 Mar 7;272(10):6539-47. [PubMed ]

1. Cheng G, Shan J, Ma J, Shi YP: [Simvastatin induced apoptosis and its effect on apoptosis-related gene expression in rat vascular smooth muscle cell] Zhejiang Da Xue Xue Bao Yi Xue Ban. 2002 Feb;31(1):11-14. [PubMed ]
2. Cheng G, Shan J, Xu G, Huang J, Ma J, Ying S, Zhu L: Apoptosis induced by simvastatin in rat vascular smooth muscle cell through Ca2+-calpain and caspase-3 dependent pathway. Pharmacol Res. 2003 Dec;48(6):571-8. [PubMed ]
3. Kaneta S, Satoh K, Kano S, Kanda M, Ichihara K: All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells. Atherosclerosis. 2003 Oct;170(2):237-43. [PubMed ]
4. Rung E, Friberg PA, Shao R, Larsson DG, Nielsen ECh, Svensson PA, Carlsson B, Carlsson LM, Billig H: Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro. Biol Reprod. 2005 Mar;72(3):538-45. Epub 2004 Sep 22. [PubMed ]
5. Fujino M, Miura S, Tanigawa H, Matsuo Y, Saku K: Counteracting effects of high density lipoprotein-cholesterol subfractions on statin-induced growth arrest. Cardiovasc Drugs Ther. 2005 Mar;19(2):113-8. [PubMed ]

1. LT-beta
2. TNF-C
3. Tumor necrosis factor C
4. Tumor necrosis factor ligand superfamily member 3

MGALGLEGRGGRLQGRGSLLLAVAGATSLVTLLLAVPITVLAVLALVPQDQGGLVTETAD
PGAQAQQGLGFQKLPEEEPETDLSPGLPAAHLIGAPLKGQGLGWETTKEQAFLTSGTQFS
DAEGLALPQDGLYYLYCLVGYRGRAPPGGGDPQGRSVTLRSSLYRAGGAYGPGTPELLLE
GAETVTPVLDPARRQGYGPLWYTSVGFGGLVQLRRGERVYVNISHPDMVDFARGKTFFGA
VMVG

• TNF (PF00229 )

• None

• 19-48

• Membrane
• single-pass type II membrane protein (Potential)

ATGGGGGCACTGGGGCTGGAGGGCAGGGGTGGGAGGCTCCAGGGGAGGGGTTCCCTCCTG
CTAGCTGTGGCAGGAGCCACTTCTCTGGTGACCTTGTTGCTGGCGGTGCCTATCACTGTC
CTGGCTGTGCTGGCCTTAGTGCCCCAGGATCAGGGAGGACTGGTAACGGAGACGGCCGAC
CCCGGGGCACAGGCCCAGCAAGGACTGGGGTTTCAGAAGCTGCCAGAGGAGGAGCCAGAA
ACAGATCTCAGCCCCGGGCTCCCAGCTGCCCACCTCATAGGCGCTCCGCTGAAGGGGCAG
GGGCTAGGCTGGGAGACGACGAAGGAACAGGCGTTTCTGACGAGCGGGACGCAGTTCTCG
GACGCCGAGGGGCTGGCGCTCCCGCAGGACGGCCTCTATTACCTCTACTGTCTCGTCGGC
TACCGGGGCCGGGCGCCCCCTGGCGGCGGGGACCCCCAGGGCCGCTCGGTCACGCTGCGC
AGCTCTCTGTACCGGGCGGGGGGCGCCTACGGGCCGGGCACTCCCGAGCTGCTGCTCGAG
GGCGCCGAGACGGTGACTCCAGTGCTGGACCCGGCCAGGAGACAAGGGTACGGGCCTCTC
TGGTACACGAGCGTGGGGTTCGGCGGCCTGGTGCAGCTCCGGAGGGGCGAGAGGGTGTAC
GTCAACATCAGTCACCCCGATATGGTGGACTTCGCGAGAGGGAAGACCTTCTTTGGGGCC
GTGATGGTGGGGTGA

1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed ]
2. Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, Ware CF: Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell. 1993 Mar 26;72(6):847-56. [PubMed ]
3. Warzocha K, Renard N, Charlot C, Bienvenu J, Coiffier B, Salles G: Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas. Biochem Biophys Res Commun. 1997 Sep 18;238(2):273-6. [PubMed ]

1. Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R, Campbell C, Gracie JA, Liew FY, McInnes IB: A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003 Feb 1;170(3):1524-30. [PubMed ]
2. Frick M, Dulak J, Cisowski J, Jozkowicz A, Zwick R, Alber H, Dichtl W, Schwarzacher SP, Pachinger O, Weidinger F: Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells. Atherosclerosis. 2003 Oct;170(2):229-36. [PubMed ]
3. Yilmaz A, Reiss C, Tantawi O, Weng A, Stumpf C, Raaz D, Ludwig J, Berger T, Steinkasserer A, Daniel WG, Garlichs CD: HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis. Atherosclerosis. 2004 Jan;172(1):85-93. [PubMed ]
4. Jiang JL, Jiang DJ, Tang YH, Li NS, Deng HW, Li YJ: Effect of simvastatin on endothelium-dependent vaso-relaxation and endogenous nitric oxide synthase inhibitor. Acta Pharmacol Sin. 2004 Jul;25(7):893-901. [PubMed ]
5. Tikiz C, Unlu Z, Tikiz H, Ay K, Angin A, Onur E, Var A, Tuzun C: The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters. J Bone Miner Metab. 2004;22(4):365-71. [PubMed ]

1. H12
2. Transforming protein RhoA precursor

MAAIRKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDT
AGQEDYDRLRPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKD
LRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTKDGVREVFEMATRAALQ
ARRGKKKSGCLVL

• Ras (PF00071 )

• None

• None

• Membrane
• lipid-anchor

ATGGCTGCCATCCGGAAGAAACTGGTGATTGTTGGTGATGGAGCCTGTGGAAAGACATGC
TTGCTCATAGTCTTCAGCAAGGACCAGTTCCCAGAGGTGTATGTGCCCACAGTGTTTGAG
AACTATGTGGCAGATATCGAGGTGGATGGAAAGCAGGTAGAGTTGGCTTTGTGGGACACA
GCTGGGCAGGAAGATTATGATCGCCTGAGGCCCCTCTCCTACCCAGATACCGATGTTATA
CTGATGTGTTTTTCCATCGACAGCCCTGATAGTTTAGAAAACATCCCAGAAAAGTGGACC
CCAGAAGTCAAGCATTTCTGTCCCAACGTGCCCATCATCCTGGTTGGGAATAAGAAGGAT
CTTCGGAATGATGAGCACACAAGGCGGGAGCTAGCCAAGATGAAGCAGGAGCCGGTGAAA
CCTGAAGAAGGCAGAGATATGGCAAACAGGATTGGCGCTTTTGGGTACATGGAGTGTTCA
GCAAAGACCAAAGATGGAGTGAGAGAGGTTTTTGAAATGGCTACGAGAGCTGCTCTGCAA
GCTAGACGTGGGAAGAAAAAATCTGGTTGCCTTGTCTTGTGA

1. Reynaud C, Fabre S, Jalinot P: The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in Rho signaling to the serum response element. J Biol Chem. 2000 Oct 27;275(43):33962-8. [PubMed ]
2. Klussmann E, Edemir B, Pepperle B, Tamma G, Henn V, Klauschenz E, Hundsrucker C, Maric K, Rosenthal W: Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling. FEBS Lett. 2001 Nov 2;507(3):264-8. [PubMed ]
3. Shao F, Merritt PM, Bao Z, Innes RW, Dixon JE: A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell. 2002 May 31;109(5):575-88. [PubMed ]
4. Shao F, Vacratsis PO, Bao Z, Bowers KE, Fierke CA, Dixon JE: Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):904-9. Epub 2003 Jan 21. [PubMed ]
5. Moscow JA, Morrow CS, He R, Mullenbach GT, Cowan KH: Structure and function of the 5'-flanking sequence of the human cytosolic selenium-dependent glutathione peroxidase gene (hgpx1). J Biol Chem. 1992 Mar 25;267(9):5949-58. [PubMed ]
6. Yeramian P, Chardin P, Madaule P, Tavitian A: Nucleotide sequence of human rho cDNA clone 12. Nucleic Acids Res. 1987 Feb 25;15(4):1869. [PubMed ]
7. Moscow JA, He R, Gudas JM, Cowan KH: Utilization of multiple polyadenylation signals in the human RHOA protooncogene. Gene. 1994 Jul 8;144(2):229-36. [PubMed ]
8. Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S: The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J. 1996 Apr 15;15(8):1885-93. [PubMed ]
9. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K: Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J. 1996 May 1;15(9):2208-16. [PubMed ]
10. Wei Y, Zhang Y, Derewenda U, Liu X, Minor W, Nakamoto RK, Somlyo AV, Somlyo AP, Derewenda ZS: Crystal structure of RhoA-GDP and its functional implications. Nat Struct Biol. 1997 Sep;4(9):699-703. [PubMed ]
11. 9545299 Ihara K, Muraguchi S, Kato M, Shimizu T, Shirakawa M, Kuroda S, Kaibuchi K, Hakoshima T: Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue. J Biol Chem. 1998 Apr 17;273(16):9656-66.

1. Ott C, Iwanciw D, Graness A, Giehl K, Goppelt-Struebe M: Modulation of the expression of connective tissue growth factor by alterations of the cytoskeleton. J Biol Chem. 2003 Nov 7;278(45):44305-11. Epub 2003 Sep 1. [PubMed ]
2. Porter KE, Turner NA, O'Regan DJ, Balmforth AJ, Ball SG: Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA. Cardiovasc Res. 2004 Mar 1;61(4):745-55. [PubMed ]
3. Crespo J, Martinez-Gonzalez J, Rius J, Badimon L: Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. Epub 2005 Apr 21. [PubMed ]
4. Tang D, Park HJ, Georgescu SP, Sebti SM, Hamilton AD, Galper JB: Simvastatin potentiates tumor necrosis factor alpha-mediated apoptosis of human vascular endothelial cells via the inhibition of the geranylgeranylation of RhoA. Life Sci. 2006 Sep 5;79(15):1484-92. Epub 2006 Apr 29. [PubMed ]
5. Xu H, Zeng L, Peng H, Chen S, Jones J, Chew TL, Sadeghi MM, Kanwar YS, Danesh FR: HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced "inside-out" signaling to extracellular matrix by preventing RhoA activation. Am J Physiol Renal Physiol. 2006 Nov;291(5):F995-1004. Epub 2006 Jun 13. [PubMed ]

1. B-cell surface antigen CD40
2. Bp50
3. CD40L receptor
4. CDw40
5. Tumor necrosis factor receptor superfamily member 5 precursor

MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECL
PCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCV
LHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTN
KTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPD
DLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ

• TNFR_c6 (PF00020 )

• 1-20

• 194-215

• Isoform I:Cell membrane
• single-pass type I membrane protein. Isoform II:Secreted protein

ATGGTTCGTCTGCCTCTGCAGTGCGTCCTCTGGGGCTGCTTGCTGACCGCTGTCCATCCA
GAACCACCCACTGCATGCAGAGAAAAACAGTACCTAATAAACAGTCAGTGCTGTTCTTTG
TGCCAGCCAGGACAGAAACTGGTGAGTGACTGCACAGAGTTCACTGAAACGGAATGCCTT
CCTTGCGGTGAAAGCGAATTCCTAGACACCTGGAACAGAGAGACACACTGCCACCAGCAC
AAATACTGCGACCCCAACCTAGGGCTTCGGGTCCAGCAGAAGGGCACCTCAGAAACAGAC
ACCATCTGCACCTGTGAAGAAGGCTGGCACTGTACGAGTGAGGCCTGTGAGAGCTGTGTC
CTGCACCGCTCATGCTCGCCCGGCTTTGGGGTCAAGCAGATTGCTACAGGGGTTTCTGAT
ACCATCTGCGAGCCCTGCCCAGTCGGCTTCTTCTCCAATGTGTCATCTGCTTTCGAAAAA
TGTCACCCTTGGACAAGCTGTGAGACCAAAGACCTGGTTGTGCAACAGGCAGGCACAAAC
AAGACTGATGTTGTCTGTGGTCCCCAGGATCGGCTGAGAGCCCTGGTGGTGATCCCCATC
ATCTTCGGGATCCTGTTTGCCATCCTCTTGGTGCTGGTCTTTATCAAAAAGGTGGCCAAG
AAGCCAACCAATAAGGCCCCCCACCCCAAGCAGGAACCCCAGGAGATCAATTTTCCCGAC
GATCTTCCTGGCTCCAACACTGCTGCTCCAGTGCAGGAGACTTTACATGGATGCCAACCG
GTCACCCAGGAGGATGGCAAAGAGAGTCGCATCTCAGTGCAGGAGAGACAGTGA

1. Ni CZ, Welsh K, Leo E, Chiou CK, Wu H, Reed JC, Ely KR: Molecular basis for CD40 signaling mediated by TRAF3. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10395-9. [PubMed ]
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3. Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, Avanzini MA, Marconi M, Badolato R, Ugazio AG, Levy Y, Catalan N, Durandy A, Tbakhi A, Notarangelo LD, Plebani A: Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12614-9. [PubMed ]
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