Showing drug card for Antihemophilic Factor (DB00025)

• BIOD00029
• BTD00029

• Approved
• Biotech
• Investigational

1. AHF
2. Coagulation factor VIII precursor
3. Procoagulant component
4. antihemophilic factor

1. Advate
2. Alphanate
3. Bioclate
4. Helixate
5. Helixate FS
6. Hemofil M
7. Humate-P
8. Hyate:C
9. Koate-HP
10. Kogenate
11. Kogenate FS
12. Monarc-M
13. Monoclate-P
14. ReFacto
15. Xyntha

ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFN
IAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQ
REKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCR
EGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNR
SLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLL
MDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRF
DDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIG
RKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGI
TDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNME
RDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAG
VQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKH
KMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYE
DSYEDISAYLLSKNNAIEPRSFSQNSRHPSTRQKQFNATTIPENDIEKTDPWFAHRTPMP
KIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPSPGAIDSNNSLSEMTHFRPQ
LHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPSDNLAAGTDN
TSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSW
GKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKTNKTSNNSATNRKTHIDGPSL
LIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQK
KEGPIPPDAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEG
QNFLSEKNKVVVGKGEFTKDVGLKEMVFPSSRNLFLTNLDNLHENNTHNQEKKIQEEIEK
KETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYDGAYAPVLQDFRSLNDSTNR
TKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRSKRALKQFRL
PLEETELEKRIIVDDTSTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSI
PQANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPAASYRKKDSGVQESSHFLQGAKK
NNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHI
YQKDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSK
LLDPLAWDNHYGTQIPKEEWKSQEKSPEKTAFKKKDTILSLNACESNHAIAAINEGQNKP
EIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISVEMKKEDFDIY
DEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTD
GSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGA
EPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHT
NTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHA
INGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYP
GVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITAS
GQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQ
FIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRS
TLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWR
PQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKV
KVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY

• Coagulants
• Thrombotic Agents

• B02BD02

• 20:28.16

1. Titheradge MA, Coore HG: Initial rates of pyruvate transport in mitochondria determined by an "inhibitor-stop" technique. Biochem J. 1975 Sep;150(3):553-6. [PubMed ]
2. Drugs.com
3. Wikipedia
4. RxList

• Humans and other mammals

1. Cytochrome P450 2C9 (CYP2C9)

1. Prothrombin
2. Coagulation factor X
3. Coagulation factor IX
4. Vitamin K-dependent protein C
5. Vitamin K-dependent protein S
6. Calnexin
7. von Willebrand factor
8. 78 kDa glucose-regulated protein
9. Calreticulin
10. Low-density lipoprotein receptor-related protein 1
11. Phytanoyl-CoA dioxygenase, peroxisomal
12. Asialoglycoprotein receptor 2
13. ERGIC-53 protein
14. Multiple coagulation factor deficiency protein 2

MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV

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. Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL: Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin. Blood. 2000 Mar 1;95(5):1694-702. [PubMed ]
2. Ratnoff OD, Lewis JH: Heckathorn's disease: variable functional dificiency of antihemophilic factor (factor VIII). Blood. 1975 Aug;46(2):161-73. [PubMed ]
3. Anderson DM, Shelley S, Crick N, Buraglio M: No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers. J Clin Pharmacol. 2002 Dec;42(12):1358-65. [PubMed ]
4. Piet MP, Chin S, Prince AM, Brotman B, Cundell AM, Horowitz B: The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation. Transfusion. 1990 Sep;30(7):591-8. [PubMed ]
5. Lazarchick J, Ashby MA, Lazarchick JJ, Sens DA: Mechanism of factor VIII inactivation by human antibodies. IV. Antibody binding prevents factor VIII proteolysis by thrombin. Ann Clin Lab Sci. 1986 Nov-Dec;16(6):497-501. [PubMed ]

1. Coagulation factor X precursor
2. EC 3.4.21.6
3. Stuart factor
4. Stuart- Prower factor

MGRPLHLVLLSASLAGLLLLGESLFIRREQANNILARVTRANSFLEEMKKGHLERECMEE
TCSYEEAREVFEDSDKTNEFWNKYKDGDQCETSPCQNQGKCKDGLGEYTCTCLEGFEGKN
CELFTRKLCSLDNGDCDQFCHEEQNSVVCSCARGYTLADNGKACIPTGPYPCGKQTLERR
KRSVAQATSSSGEAPDSITWKPYDAADLDPTENPFDLLDFNQTQPERGDNNLTRIVGGQE
CKDGECPWQALLINEENEGFCGGTILSEFYILTAAHCLYQAKRFKVRVGDRNTEQEEGGE
AVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITFRMNVAPACLPERDWAESTLMTQKTGI
VSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFIITQNMFCAGYDTKQEDACQGDSG
GPHVTRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRGLPKAKSHAPE
VITSSPLK

• Selective cleavage of Arg!Thr and then Arg!Ile bonds in prothrombin to form thrombin

• EGF (PF00008 )
• Trypsin (PF00089 )
• Gla (PF00594 )

• 1-31

• 7-26

• Cytoplasmic

CCTCCCTGGCTGGCCTCCTGCTGCTCGGGGAAAGTCTGTTCATCCGCAGGGAGCAGGCCA
ACAACATCCTGGCGAGGGTCACGAGGGCCAATTCCTTTCTTGAAGAGATGAAGAAAGGAC
ACCTCGAAAGAGAGTGCATGGAAGAGACCTGCTCATACGAAGAGGCCCGCGAGGTCTTTG
AGGACAGCGACAAGACGAATGAATTCTGGAATAAATACAAAGATGGCGACCAGTGTGAGA
CCAGTCCTTGCCAGAACCAGGGCAAATGTAAAGACGGCCTCGGGGAATACACCTGCACCT
GTTTAGAAGGATTCGAAGGCAAAAACTGTGAATTATTCACACGGAAGCTCTGCAGCCTGG
ACAACGGGGACTGTGACCAGTTCTGCCACGAGGAACAGAACTCTGTGGTGTGCTCCTGCG
CCCGCGGGTACACCCTGGCTGACAACGGCAAGGCCTGCATTCCCACAGGGCCCTACCCCT
GTGGGAAACAGACCCTGGAACGCAGGAAGAGGTCAGTGGCCCAGGCCACCAGCAGCAGCG
GGGAGGCCCCTGACAGCATCACATGGAAGCCATATGATGCAGCCGACCTGGACCCCACCG
AGAACCCCTTCGACCTGCTTGACTTCAACCAGACGCAGCCTGAGAGGGGCGACAACAACC
TCACCAGGATCGTGGGAGGCCAGGAATGCAAGGACGGGGAGTGTCCCTGGCAGGCCCTGC
TCATCAATGAGGAAAACGAGGGTTTCTGTGGTGGAACTATTCTGAGCGAGTTCTACATCC
TAACGGCAGCCCACTGTCTCTACCAAGCCAAGAGATTCAAGGTGAGGGTAGGGGACCGGA
ACACGGAGCAGGAGGAGGGCGGTGAGGCGGTGCACGAGGTGGAGGTGGTCATCAAGCACA
ACCGGTTCACAAAGGAGACCTATGACTTCGACATCGCCGTGCTCCGGCTCAAGACCCCCA
TCACCTTCCGCATGAACGTGGCGCCTGCCTGCCTCCCCGAGCGTGACTGGGCCGAGTCCA
CGCTGATGACGCAGAAGACGGGGATTGTGAGCGGCTTCGGGCGCACCCACGAGAAGGGCC
GGCAGTCCACCAGGCTCAAGATGCTGGAGGTGCCCTACGTGGACCGCAACAGCTGCAAGC
TGTCCAGCAGCTTCATCATCACCCAGAACATGTTCTGTGCCGGCTACGACACCAAGCAGG
AGGATGCCTGCCAGGGGGACAGCGGGGGCCCGCACGTCACCCGCTTCAAGGACACCTACT
TCGTGACAGGCATCGTCAGCTGGGGAGAGAGCTGTGCCCGTAAGGGGAAGTACGGGATCT
ACACCAAGGTCACCGCCTTCCTCAAGTGGATCGACAGGTCCATGAAAACCAGGGGCTTGC
CCAAGGCCAAGAGCCATGCCCCGGAGGTCATAACGTCCTCTCCATTAAAGTGA

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. Messier TL, Pittman DD, Long GL, Kaufman RJ, Church WR: Cloning and expression in COS-1 cells of a full-length cDNA encoding human coagulation factor X. Gene. 1991 Mar 15;99(2):291-4. [PubMed ]
3. Fung MR, Hay CW, MacGillivray RT: Characterization of an almost full-length cDNA coding for human blood coagulation factor X. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3591-5. [PubMed ]
4. Jagadeeswaran P, Reddy SV, Rao KJ, Hamsabhushanam K, Lyman G: Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X. Gene. 1989 Dec 14;84(2):517-9. [PubMed ]
5. Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P: Isolation and characterization of human blood-coagulation factor X cDNA. Gene. 1986;41(2-3):311-4. [PubMed ]
6. Leytus SP, Foster DC, Kurachi K, Davie EW: Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry. 1986 Sep 9;25(18):5098-102. [PubMed ]
7. Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW: Characterization of a cDNA coding for human factor X. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3699-702. [PubMed ]
8. McMullen BA, Fujikawa K, Kisiel W, Sasagawa T, Howald WN, Kwa EY, Weinstein B: Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid. Biochemistry. 1983 Jun 7;22(12):2875-84. [PubMed ]
9. Inoue K, Morita T: Identification of O-linked oligosaccharide chains in the activation peptides of blood coagulation factor X. The role of the carbohydrate moieties in the activation of factor X. Eur J Biochem. 1993 Nov 15;218(1):153-63. [PubMed ]
10. Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W: Structure of human des(1-45) factor Xa at 2.2 A resolution. J Mol Biol. 1993 Aug 5;232(3):947-66. [PubMed ]
11. 9618463 Kamata K, Kawamoto H, Honma T, Iwama T, Kim SH: Structural basis for chemical inhibition of human blood coagulation factor Xa. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6630-5.

1. Freedman J, Mody M, Lazarus AH, Dewar L, Song S, Blanchette VS, Garvey MB, Ofosu FA: Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C). Am J Hematol. 2002 Mar;69(3):192-9. [PubMed ]
2. BLATRIX C, SOULIER JP: [Preparation of a fraction rich in prothrombin, proconvertin, Stuart factor and antihemophilic factor B (P.P.B. fraction)] Pathol Biol (Paris). 1959 Dec;7:2477-86. [PubMed ]
3. LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF STUART FACTOR (FACTOR X) BY ACTIVATED ANTIHEMOPHILIC FACTOR (ACTIVATED FACTOR 8). Biochemistry. 1965 Jan;4:113-20. [PubMed ]
4. Radnoff OD, Saito H: Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500). Proc Soc Exp Biol Med. 1975 Jan;148(1):177-82. [PubMed ]
5. Orthner CL: Characterization of proteases in AHF concentrates: effect on factor VIII:von Willebrand protein as assessed by high-pressure gel permeation chromatography. J Lab Clin Med. 1984 Nov;104(5):816-28. [PubMed ]

1. Christmas factor
2. Coagulation factor IX precursor
3. EC 3.4.21.22
4. PTC
5. Plasma thromboplastin component

MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP
FGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAENQKSCEPAVPFPCGR
VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRVVGGEDAKPGQFPW
QVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEETEHTEQKRNVIRII
PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF
HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE
GTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT

• Selective cleavage of Arg!Ile bond in factor X to form factor Xa

• EGF (PF00008 )
• Trypsin (PF00089 )
• Gla (PF00594 )

• 1-28

• None

• Secreted protein

ATGCAGCGCGTGAACATGATCATGGCAGAATCACCAAGCCTCATCACCATCTGCCTTTTA
GGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAAATT
CTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTT
GAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAACCACGAGAAGTTTTTGAAAAC
ACTGAAAAGACAACTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAAT
CCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCCC
TTTGGATTTGAAGGAAAGAACTGTGAATTAGATGTAACATGTAACATTAAGAATGGCAGA
TGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAAGGTGGTTTGCTCCTGTACTGAGGGA
TATCGACTTGCAGAAAACCAGAAGTCCTGTGAACCAGCAGTGCCATTTCCATGTGGAAGA
GTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGGCTGTTTTTCCTGATGTGGAC
TATGTAAATCCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAGGCACCCAATCA
TTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGG
CAGGTTGTTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAA
TGGATTGTAACTGCTGCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGT
GAACATAATATTGAGGAGACAGAACATACAGAGCAAAAGCGAAATGTGATTCGAGCAATT
ATTCCTCACCACAACTACAATGCAGCTATTAATAAGTACAACCATGACATTGCCCTTCTG
GAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTACACCTATTTGCATTGCTGACAAG
GAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGTGGCTGGGCAAGAGTC
TTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGTTGACCGA
GCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTC
CATGAAGGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTG
GAAGGGACCAGTTTCTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGC
AAATATGGAATATATACCAAGGTATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAG
CTCACTTAA

1. Montejo JM, Magallon M, Tizzano E, Solera J: Identification of twenty-one new mutations in the factor IX gene by SSCP analysis. Hum Mutat. 1999;13(2):160-5. [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. Hopfner KP, Lang A, Karcher A, Sichler K, Kopetzki E, Brandstetter H, Huber R, Bode W, Engh RA: Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding. Structure. 1999 Aug 15;7(8):989-96. [PubMed ]
4. Wulff K, Bykowska K, Lopaciuk S, Herrmann FH: Molecular analysis of hemophilia B in Poland: 12 novel mutations of the factor IX gene. Acta Biochim Pol. 1999;46(3):721-6. [PubMed ]
5. Vidal F, Farssac E, Altisent C, Puig L, Gallardo D: Factor IX gene sequencing by a simple and sensitive 15-hour procedure for haemophilia B diagnosis: identification of two novel mutations. Br J Haematol. 2000 Nov;111(2):549-51. [PubMed ]
6. Arruda VR, Hagstrom JN, Deitch J, Heiman-Patterson T, Camire RM, Chu K, Fields PA, Herzog RW, Couto LB, Larson PJ, High KA: Posttranslational modifications of recombinant myotube-synthesized human factor IX. Blood. 2001 Jan 1;97(1):130-8. [PubMed ]
7. Onay UV, Kavakli K, Kilinc Y, Gurgey A, Aktuglu G, Kemahli S, Ozbek U, Caglayan SH: Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations. Br J Haematol. 2003 Feb;120(4):656-9. [PubMed ]
8. Espinos C, Casana P, Haya S, Cid AR, Aznar JA: Molecular analyses in hemophilia B families: identification of six new mutations in the factor IX gene. Haematologica. 2003 Feb;88(2):235-6. [PubMed ]
9. Baron M, Norman DG, Harvey TS, Handford PA, Mayhew M, Tse AG, Brownlee GG, Campbell ID: The three-dimensional structure of the first EGF-like module of human factor IX: comparison with EGF and TGF-alpha. Protein Sci. 1992 Jan;1(1):81-90. [PubMed ]
10. Ludwig M, Sabharwal AK, Brackmann HH, Olek K, Smith KJ, Birktoft JJ, Bajaj SP: Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX. Blood. 1992 Mar 1;79(5):1225-32. [PubMed ]
11. 1517205 Nishimura H, Takao T, Hase S, Shimonishi Y, Iwanaga S: Human factor IX has a tetrasaccharide O-glycosidically linked to serine 61 through the fucose residue. J Biol Chem. 1992 Sep 5;267(25):17520-5.
12. 1615485 Taylor SA, Duffin J, Cameron C, Teitel J, Garvey B, Lillicrap DP: Characterization of the original Christmas disease mutation (cysteine 206----serine): from clinical recognition to molecular pathogenesis. Thromb Haemost. 1992 Jan 23;67(1):63-5.
13. 1634040 Sommer SS: Assessing the underlying pattern of human germline mutations: lessons from the factor IX gene. FASEB J. 1992 Jul;6(10):2767-74.
14. 1854745 Huang LH, Cheng H, Pardi A, Tam JP, Sweeney WV: Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX. Biochemistry. 1991 Jul 30;30(30):7402-9.
15. 1902289 Sarkar G, Cassady JD, Pyeritz RE, Gilchrist GS, Sommer SS: Isoleucine397 is changed to threonine in two females with hemophilia B. Nucleic Acids Res. 1991 Mar 11;19(5):1165.
16. 1958666 Miyata T, Sakai T, Sugimoto M, Naka H, Yamamoto K, Yoshioka A, Fukui H, Mitsui K, Kamiya K, Umeyama H, et al.: Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities. Biochemistry. 1991 Nov 26;30(47):11286-91.
17. 2129367 Iwanaga S, Nishimura H, Kawabata S, Kisiel W, Hase S, Ikenaka T: A new trisaccharide sugar chain linked to a serine residue in the first EGF-like domain of clotting factors VII and IX and protein Z. Adv Exp Med Biol. 1990;281:121-31.
18. 2162822 Bertina RM, van der Linden IK, Mannucci PM, Reinalda-Poot HH, Cupers R, Poort SR, Reitsma PH: Mutations in hemophilia Bm occur at the Arg180-Val activation site or in the catalytic domain of factor IX. J Biol Chem. 1990 Jul 5;265(19):10876-83.
19. 2339358 Wang NS, Zhang M, Thompson AR, Chen SH: Factor IX Chongqing: a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B. Thromb Haemost. 1990 Feb 19;63(1):24-6.
20. 2372509 Taylor SA, Liddell MB, Peake IR, Bloom AL, Lillicrap DP: A mutation adjacent to the beta cleavage site of factor IX (valine 182 to leucine) results in mild haemophilia Bm. Br J Haematol. 1990 Jun;75(2):217-21.
21. 2472424 Chen SH, Thompson AR, Zhang M, Scott CR: Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins. J Clin Invest. 1989 Jul;84(1):113-8.
22. 2511201 Nishimura H, Kawabata S, Kisiel W, Hase S, Ikenaka T, Takao T, Shimonishi Y, Iwanaga S: Identification of a disaccharide (Xyl-Glc) and a trisaccharide (Xyl2-Glc) O-glycosidically linked to a serine residue in the first epidermal growth factor-like domain of human factors VII and IX and protein Z and bovine protein Z. J Biol Chem. 1989 Dec 5;264(34):20320-5.
23. 2592373 Suehiro K, Kawabata S, Miyata T, Takeya H, Takamatsu J, Ogata K, Kamiya T, Saito H, Niho Y, Iwanaga S: Blood clotting factor IX BM Nagoya. Substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase. J Biol Chem. 1989 Dec 15;264(35):21257-65.
24. 2713493 Monroe DM, McCord DM, Huang MN, High KA, Lundblad RL, Kasper CK, Roberts HR: Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo. Blood. 1989 May 1;73(6):1540-4.
25. 2714791 Attree O, Vidaud D, Vidaud M, Amselem S, Lavergne JM, Goossens M: Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior. Genomics. 1989 Apr;4(3):266-72.
26. 2738071 Ware J, Diuguid DL, Liebman HA, Rabiet MJ, Kasper CK, Furie BC, Furie B, Stafford DW: Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties. J Biol Chem. 1989 Jul 5;264(19):11401-6.
27. 2743975 Green PM, Bentley DR, Mibashan RS, Nilsson IM, Giannelli F: Molecular pathology of haemophilia B. EMBO J. 1989 Apr;8(4):1067-72.
28. 2753873 Sakai T, Yoshioka A, Yamamoto K, Niinomi K, Fujimura Y, Fukui H, Miyata T, Iwanaga S: Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine. J Biochem (Tokyo). 1989 May;105(5):756-9.
29. 2773937 Koeberl DD, Bottema CD, Buerstedde JM, Sommer SS: Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG. Am J Hum Genet. 1989 Sep;45(3):448-57.
30. 2775660 Liddell MB, Peake IR, Taylor SA, Lillicrap DP, Giddings JC, Bloom AL: Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145. Br J Haematol. 1989 Aug;72(4):556-60.
31. 2994716 Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736-50.
32. 3009023 Bentley AK, Rees DJ, Rizza C, Brownlee GG: Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4. Cell. 1986 May 9;45(3):343-8.
33. 3243764 Sugimoto M, Miyata T, Kawabata S, Yoshioka A, Fukui H, Takahashi H, Iwanaga S: Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain. J Biochem (Tokyo). 1988 Dec;104(6):878-80.
34. 3340835 Stoflet ES, Koeberl DD, Sarkar G, Sommer SS: Genomic amplification with transcript sequencing. Science. 1988 Jan 29;239(4839):491-4.
35. 3401602 Ware J, Davis L, Frazier D, Bajaj SP, Stafford DW: Genetic defect responsible for the dysfunctional protein: factor IXLong Beach. Blood. 1988 Aug;72(2):820-2.
36. 3790720 Davis LM, McGraw RA, Ware JL, Roberts HR, Stafford DW: Factor IXAlabama: a point mutation in a clotting protein results in hemophilia B. Blood. 1987 Jan;69(1):140-3.
37. 3857619 McGraw RA, Davis LM, Noyes CM, Lundblad RL, Roberts HR, Graham JB, Stafford DW: Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX. Proc Natl Acad Sci U S A. 1985 May;82(9):2847-51.
38. 6089357 Jagadeeswaran P, Lavelle DE, Kaul R, Mohandas T, Warren ST: Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment. Somat Cell Mol Genet. 1984 Sep;10(5):465-73.
39. 6329734 Anson DS, Choo KH, Rees DJ, Giannelli F, Gould K, Huddleston JA, Brownlee GG: The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053-60.
40. 6425296 Morita T, Isaacs BS, Esmon CT, Johnson AE: Derivatives of blood coagulation factor IX contain a high affinity Ca2+-binding site that lacks gamma-carboxyglutamic acid. J Biol Chem. 1984 May 10;259(9):5698-704.
41. 659613 Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38.
42. 6603618 Noyes CM, Griffith MJ, Roberts HR, Lundblad RL: Identification of the molecular defect in factor IX Chapel Hill: substitution of histidine for arginine at position 145. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4200-2.
43. 6687940 Jaye M, de la Salle H, Schamber F, Balland A, Kohli V, Findeli A, Tolstoshev P, Lecocq JP: Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic Acids Res. 1983 Apr 25;11(8):2325-35.
44. 6688526 McMullen BA, Fujikawa K, Kisiel W: The occurrence of beta-hydroxyaspartic acid in the vitamin K-dependent blood coagulation zymogens. Biochem Biophys Res Commun. 1983 Aug 30;115(1):8-14.
45. 7547952 Freedman SJ, Furie BC, Furie B, Baleja JD: Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich domain of factor IX. Biochemistry. 1995 Sep 26;34(38):12126-37.
46. 7606779 Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D: The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. Cell. 1995 Jul 14;82(1):131-41.
47. 7713897 Freedman SJ, Furie BC, Furie B, Baleja JD: Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy. J Biol Chem. 1995 Apr 7;270(14):7980-7.
48. 7981722 Caglayan SH, Vielhaber E, Gursel T, Aktuglu G, Sommer SS: Identification of mutations in four hemophilia B patients of Turkish origin, including a novel deletion of base 6411. Hum Mutat. 1994;4(2):163-5.
49. 8076946 Aguilar-Martinez P, Romey MC, Schved JF, Gris JC, Demaille J, Claustres M: Factor IX gene mutations causing haemophilia B: comparison of SSC screening versus systematic DNA sequencing and diagnostic applications. Hum Genet. 1994 Sep;94(3):287-90.
50. 8199596 Aguilar-Martinez P, Romey MC, Gris JC, Schved JF, Demaille J, Claustres M: A novel mutation (Val-373 to Glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient. Hum Mutat. 1994;3(2):156-8.
51. 8236150 de la Salle C, Charmantier JL, Baas MJ, Schwartz A, Wiesel ML, Grunebaum L, Cazenave JP: A deletion located in the 3' non translated part of the factor IX gene responsible for mild haemophilia B. Thromb Haemost. 1993 Aug 2;70(2):370-1.
52. 8257988 David D, Rosa HA, Pemberton S, Diniz MJ, Campos M, Lavinha J: Single-strand conformation polymorphism (SSCP) analysis of the molecular pathology of hemophilia B. Hum Mutat. 1993;2(5):355-61.
53. 8295821 de la Salle C, Charmantier JL, Ravanat C, Ohlmann P, Hartmann ML, Schuhler S, Bischoff R, Ebel C, Roecklin D, Balland A, et al.: The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa. Nouv Rev Fr Hematol. 1993;35(5):473-80.
54. 8392713 Giannelli F, Green PM, High KA, Sommer S, Poon MC, Ludwig M, Schwaab R, Reitsma PH, Goossens M, Yoshioka A, et al.: Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993. Nucleic Acids Res. 1993 Jul 1;21(13):3075-87.
55. 8663165 Freedman SJ, Blostein MD, Baleja JD, Jacobs M, Furie BC, Furie B: Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX. J Biol Chem. 1996 Jul 5;271(27):16227-36.
56. 8680410 Wulff K, Schroder W, Wehnert M, Herrmann FH: Twenty-five novel mutations of the factor IX gene in haemophilia B. Hum Mutat. 1995;6(4):346-8.
57. 8833911 Chu K, Wu SM, Stanley T, Stafford DW, High KA: A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. J Clin Invest. 1996 Oct 1;98(7):1619-25.
58. 9047312 Li L, Darden TA, Freedman SJ, Furie BC, Furie B, Baleja JD, Smith H, Hiskey RG, Pedersen LG: Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm. Biochemistry. 1997 Feb 25;36(8):2132-8.
59. 9222764 Caglayan SH, Gokmen Y, Aktuglu G, Gurgey A, Sommer SS: Mutations associated with hemophilia B in Turkish patients. Hum Mutat. 1997;10(1):76-9.
60. 9452115 David D, Moreira I, Morais S, de Deus G: Five novel factor IX mutations in unrelated hemophilia B patients. Hum Mutat. 1998;Suppl 1:S301-3.
61. 9590153 Chan V, Chan VW, Yip B, Chim CS, Chan TK: Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome. Am J Hematol. 1998 May;58(1):72-6.
62. 9600455 Heit JA, Thorland EC, Ketterling RP, Lind TJ, Daniels TM, Zapata RE, Ordonez SM, Kasper CK, Sommer SS: Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern. Hum Mutat. 1998;11(5):372-6.

1. Hule V: [Factor IX inhibitor (antihemophilic factor B, PTC) in a woman] Vnitr Lek. 1975 Mar;21(3):274-7. [PubMed ]
2. LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF ANTIHEMOPHILIC FACTOR (FACTOR 8) BY ACTIVATED CHRISTMAS FACTOR (ACTIVATED FACTOR9 9). Biochemistry. 1964 Nov;3:1720-5. [PubMed ]
3. Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736-50. [PubMed ]
4. Prince AM, Horowitz B, Brotman B, Huima T, Richardson L, van den Ende MC: Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether. Vox Sang. 1984;46(1):36-43. [PubMed ]
5. Hoofnagle JH, Gerety RJ, Thiel J, Barker LF: The prevalence of hepatitis B surface antigen in commercially prepared plasma products. J Lab Clin Med. 1976 Jul;88(1):102-13. [PubMed ]

1. Anticoagulant protein C
2. Autoprothrombin IIA
3. Blood coagulation factor XIV
4. EC 3.4.21.69
5. Vitamin K-dependent protein C precursor

MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRANSFLEELRHSSLERECI
EEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCASLCCGHGTCIDGIGSFSC
DCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVK
FPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMTRRGDSPWQVVLLDSKKKLACGA
VLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKWELDLDIKEVFVHPNYSKSTTDNDI
ALLHLAQPATLSQTIVPICLPDSGLAERELNQAGQETLVTGWGYHSSREKEAKRNRTFVL
NFIKIPVVPHNECSEVMSNMVSENMLCAGILGDRQDACEGDSGGPMVASFHGTWFLVGLV
SWGEGCGLLHNYGVYTKVSRYLDWIHGHIRDKEAPQKSWAP

• Degradation of blood coagulation factors Va and VIIIa

• EGF (PF00008 )
• Trypsin (PF00089 )
• Gla (PF00594 )

• 1-32

• None

• Cytoplasmic

ATGTGGCAGCTCACAAGCCTCCTGCTGTTCGTGGCCACCTGGGGAATTTCCGGCACACCA
GCTCCTCTTGACTCAGTGTTCTCCAGCAGCGAGCGTGCCCACCAGGTGCTGCGGATCCGC
AAACGTGCCAACTCCTTCCTGGAGGAGCTCCGTCACAGCAGCCTGGAGCGGGAGTGCATA
GAGGAGATCTGTGACTTCGAGGAGGCCAAGGAAATTTTCCAAAATGTGGATGACACACTG
GCCTTCTGGTCCAAGCACGTCGACGGTGACCAGTGCTTGGTCTTGCCCTTGGAGCACCCG
TGCGCCAGCCTGTGCTGCGGGCACGGCACGTGCATCGACGGCATCGGCAGCTTCAGCTGC
GACTGCCGCAGCGGCTGGGAGGGCCGCTTCTGCCAGCGCGAGGTGAGCTTCCTCAATTGC
TCTCTGGACAACGGCGGCTGCACGCATTACTGCCTAGAGGAGGTGGGCTGGCGGCGCTGT
AGCTGTGCGCCTGGCTACAAGCTGGGGGACGACCTCCTGCAGTGTCACCCCGCAGTGAAG
TTCCCTTGTGGGAGGCCCTGGAAGCGGATGGAGAAGAAGCGCAGTCACCTGAAACGAGAC
ACAGAAGACCAAGAAGACCAAGTAGATCCGCGGCTCATTGATGGGAAGATGACCAGGCGG
GGAGACAGCCCCTGGCAGGTGGTCCTGCTGGACTCAAAGAAGAAGCTGGCCTGCGGGGCA
GTGCTCATCCACCCCTCCTGGGTGCTGACAGCGGCCCACTGCATGGATGAGTCCAAGAAG
CTCCTTGTCAGGCTTGGAGAGTATGACCTGCGGCGCTGGGAGAAGTGGGAGCTGGACCTG
GACATCAAGGAGGTCTTCGTCCACCCCAACTACAGCAAGAGCACCACCGACAATGACATC
GCACTGCTGCACCTGGCCCAGCCCGCCACCCTCTCGCAGACCATAGTGCCCATCTGCCTC
CCGGACAGCGGCCTTGCAGAGCGCGAGCTCAATCAGGCCGGCCAGGAGACCCTCGTGACG
GGCTGGGGCTACCACAGCAGCCGAGAGAAGGAGGCCAAGAGAAACCGCACCTTCGTCCTC
AACTTCATCAAGATTCCCGTGGTCCCGCACAATGAGTGCAGCGAGGTCATGAGCAACATG
GTGTCTGAGAACATGCTGTGTGCGGGCATCCTCGGGGACCGGCAGGATGCCTGCGAGGGC
GACAGTGGGGGGCCCATGGTCGCCTCCTTCCACGGCACCTGGTTCCTGGTGGGCCTGGTG
AGCTGGGGTGAGGGCTGTGGGCTCCTTCACAACTACGGCGTTTACACCAAAGTCAGCCGC
TACCTCGACTGGATCCATGGGCACATCAGAGACAAGGAAGCCCCCCAGAAGAGCTGGGCA
CCTTAG

1. Gandrille S, Vidaud M, Aiach M, Alhenc-Gelas M, Fischer AM, Gouault-Heilman M, Toulon P, Fiessinger JN, Goossens M: Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis. Hum Mutat. 1992;1(6):491-500. [PubMed ]
2. Bovill EG, Tomczak JA, Grant B, Bhushan F, Pillemer E, Rainville IR, Long GL: Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations. Blood. 1992 Mar 15;79(6):1456-65. [PubMed ]
3. Grundy CB, Chisholm M, Kakkar VV, Cooper DN: A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. Hum Genet. 1992 Aug;89(6):683-4. [PubMed ]
4. Grundy CB, Schulman S, Tengborn L, Kakkar VV, Cooper DN: Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. Hum Genet. 1992 Aug;89(6):685-6. [PubMed ]
5. Harris RJ, Ling VT, Spellman MW: O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C. J Biol Chem. 1992 Mar 15;267(8):5102-7. [PubMed ]
6. Yamamoto K, Matsushita T, Sugiura I, Takamatsu J, Iwasaki E, Wada H, Deguchi K, Shirakawa S, Saito H: Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. J Lab Clin Med. 1992 Jun;119(6):682-9. [PubMed ]
7. Sugahara Y, Miura O, Yuen P, Aoki N: Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation. Blood. 1992 Jul 1;80(1):126-33. [PubMed ]
8. Miletich JP, Broze GJ Jr: Beta protein C is not glycosylated at asparagine 329. The rate of translation may influence the frequency of usage at asparagine-X-cysteine sites. J Biol Chem. 1990 Jul 5;265(19):11397-404. [PubMed ]
9. Reitsma PH, Poort SR, Allaart CF, Briet E, Bertina RM: The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects. Blood. 1991 Aug 15;78(4):890-4. [PubMed ]
10. Romeo G, Hassan HJ, Staempfli S, Roncuzzi L, Cianetti L, Leonardi A, Vicente V, Mannucci PM, Bertina R, Peschle C, et al.: Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene. Proc Natl Acad Sci U S A. 1987 May;84(9):2829-32. [PubMed ]
11. 2602169 Grundy C, Chitolie A, Talbot S, Bevan D, Kakkar V, Cooper DN: Protein C London 1: recurrent mutation at Arg 169 (CGG----TGG) in the protein C gene causing thrombosis. Nucleic Acids Res. 1989 Dec 25;17(24):10513.
12. 2991859 Beckmann RJ, Schmidt RJ, Santerre RF, Plutzky J, Crabtree GR, Long GL: The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs. Nucleic Acids Res. 1985 Jul 25;13(14):5233-47.
13. 2991887 Foster DC, Yoshitake S, Davie EW: The nucleotide sequence of the gene for human protein C. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4673-7.
14. 3511471 Plutzky J, Hoskins JA, Long GL, Crabtree GR: Evolution and organization of the human protein C gene. Proc Natl Acad Sci U S A. 1986 Feb;83(3):546-50.
15. 6589623 Foster D, Davie EW: Characterization of a cDNA coding for human protein C. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4766-70.
16. 7605880 Millar DS, Bevan D, Chitolie A, Reynaud J, Chisholm M, Kakkar VV, Cooper DN: Three novel mutations in the protein C (PROC) gene causing venous thrombosis. Blood Coagul Fibrinolysis. 1995 Apr;6(2):138-40.
17. 7792728 Lind B, Schwartz M, Thorsen S: Six different point mutations in seven Danish families with symptomatic protein C deficiency. Thromb Haemost. 1995 Feb;73(2):186-93.
18. 7841323 Millar DS, Allgrove J, Rodeck C, Kakkar VV, Cooper DN: A homozygous deletion/insertion mutation in the protein C (PROC) gene causing neonatal Purpura fulminans: prenatal diagnosis in an at-risk pregnancy. Blood Coagul Fibrinolysis. 1994 Aug;5(4):647-9.
19. 7841324 Witt I, Beck S, Seydewitz HH, Tasangil C, Schenck W: A novel homozygous missense mutation (Val 325-->Ala) in the protein C gene causing neonatal purpura fulminans. Blood Coagul Fibrinolysis. 1994 Aug;5(4):651-3.
20. 7865674 Zheng YZ, Sakata T, Matsusue T, Umeyama H, Kato H, Miyata T: Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling. Blood Coagul Fibrinolysis. 1994 Oct;5(5):687-96.
21. 7878626 Long GL, Tomczak JA, Rainville IR, Dreyfus M, Schramm W, Schwarz HP: Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations. Thromb Haemost. 1994 Oct;72(4):526-33.
22. 7919373 Gandrille S, Jude B, Alhenc-Gelas M, Emmerich J, Aiach M: First de novo mutations in the protein C gene of two patients with type I deficiency: a missense mutation and a splice site deletion. Blood. 1994 Oct 15;84(8):2566-70.
23. 7974343 Gaussem P, Gandrille S, Duchemin J, Emmerich J, Alhenc-Gelas M, Aillaud MF, Aiach M: Influence of six mutations of the protein C gene on the Gla domain conformation and calcium affinity. Thromb Haemost. 1994 Jun;71(6):748-54.
24. 8003977 Fisher CL, Greengard JS, Griffin JH: Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen. Protein Sci. 1994 Apr;3(4):588-99.
25. 8292730 Tsay W, Greengard JS, Montgomery RR, McPherson RA, Fucci JC, Koerper MA, Coughlin J, Griffin JH: Genetic mutations in ten unrelated American patients with symptomatic type 1 protein C deficiency. Blood Coagul Fibrinolysis. 1993 Oct;4(5):791-6.
26. 8324221 Gandrille S, Alhenc-Gelas M, Gaussem P, Aillaud MF, Dupuy E, Juhan-Vague I, Aiach M: Five novel mutations located in exons III and IX of the protein C gene in patients presenting with defective protein C anticoagulant activity. Blood. 1993 Jul 1;82(1):159-68.
27. 8398832 Marchetti G, Patracchini P, Gemmati D, Castaman G, Rodeghiero F, Wacey A, Cooper DN, Tuddenham EG, Bernardi F: Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket. Br J Haematol. 1993 Jun;84(2):285-9.
28. 8446940 Reitsma PH, Poort SR, Bernardi F, Gandrille S, Long GL, Sala N, Cooper DN: Protein C deficiency: a database of mutations. For the Protein C & S Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1993 Jan 11;69(1):77-84.
29. 8477066 Mimuro J, Muramatsu S, Kaneko M, Yoshitake S, Iijima K, Nakamura K, Sakata Y, Matsuda M: An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency. Int J Hematol. 1993 Jan;57(1):9-14.
30. 8499565 Poort SR, Pabinger-Fasching I, Mannhalter C, Reitsma PH, Bertina RM: Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency. Blood Coagul Fibrinolysis. 1993 Apr;4(2):273-80.
31. 8499568 Millar DS, Grundy CB, Bignell P, Moffat EH, Martin R, Kakkar VV, Cooper DN: A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis. Blood Coagul Fibrinolysis. 1993 Apr;4(2):345-7.
32. 8829639 Ireland HA, Boisclair MD, Taylor J, Thompson E, Thein SL, Girolami A, De Caterina M, Scopacasa F, De Stefano V, Leone G, Finazzi G, Cohen H, Lane DA: Two novel (R(-11)C; T394D) and two repeat missense mutations in the protein C gene associated with venous thrombosis in six kindreds. Hum Mutat. 1996;7(2):176-9.
33. 9003757 Mather T, Oganessyan V, Hof P, Huber R, Foundling S, Esmon C, Bode W: The 2.8 A crystal structure of Gla-domainless activated protein C. EMBO J. 1996 Dec 16;15(24):6822-31.
34. 9798967 Couture P, Demers C, Morissette J, Delage R, Jomphe M, Couture L, Simard J: Type I protein C deficiency in French Canadians: evidence of a founder effect and association of specific protein C gene mutations with plasma protein C levels. Thromb Haemost. 1998 Oct;80(4):551-6.

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Vitamin K-dependent protein S precursor

MRVLGGRCGALLACLLLVLPVSEANFLSKQQASQVLVRKRRANSLLEETKQGNLERECIE
ELCNKEEAREVFENDPETDYFYPKYLVCLRSFQTGLFTAARQSTNAYPDLRSCVNAIPDQ
CSPLPCNEDGYMSCKDGKASFTCTCKPGWQGEKCEFDINECKDPSNINGGCSQICDNTPG
SYHCSCKNGFVMLSNKKDCKDVDECSLKPSICGTAVCKNIPGDFECECPEGYRYNLKSKS
CEDIDECSENMCAQLCVNYPGGYTCYCDGKKGFKLAQDQKSCEVVSVCLPLNLDTKYELL
YLAEQFAGVVLYLKFRLPEISRFSAEFDFRTYDSEGVILYAESIDHSAWLLIALRGGKIE
VQLKNEHTSKITTGGDVINNGLWNMVSVEELEHSISIKIAKEAVMDINKPGPLFKPENGL
LETKVYFAGFPRKVESELIKPINPRLDGCIRSWNLMKQGASGIKEIIQEKQNKHCLVTVE
KGSYYPGSGIAQFHIDYNNVSSAEGWHVNVTLNIRPSTGTGVMLALVSGNNTVPFAVSLV
DSTSEKSQDILLSVENTVIYRIQALSLCSDQQSHLEFRVNRNNLELSTPLKIETISHEDL
QRQLAVLDKAMKAKVATYLGGLPDVPFSATPVNAFYNGCMEVNINGVQLDLDEAISKHND
IRAHSCPSVWKKTKNS

• EGF (PF00008 )
• Laminin_G_1 (PF00054 )
• Gla (PF00594 )
• Laminin_G_2 (PF02210 )
• EGF_CA (PF07645 )

• 1-24

• None

• Secreted protein

ATGAGGGTCCTGGGTGGGCGCTGCGGGGCGCCGCTGGCGTGTCTCCTCCTAGTGCTTCCC
GTCTCAGAGGCAAACCTTCTGTCAAAGCAACAGGCTTCACAAGTCCTGGTTAGGAAGCGT
CGTGCAAATTCTTTACTTGAAGAAACCAAACAGGGTAATCTTGAAAGAGAATGCATCGAA
GAACTGTGCAATAAAGAAGAAGCCAGGGAGGTCTTTGAAAATGACCCGGAAACGGATTAT
TTTTATCCAAAATACTTAGTTTGTCTTCGCTCTTTTCAAACTGGGTTATTCACTGCTGCA
CGTCAGTCAACTAATGCTTATCCTGACCTAAGAAGCTGTGTCAATGCCATTCCAGACCAG
TGTAGTCCTCTGCCATGCAATGAAGATGGATATATGAGCTGCAAAGATGGAAAAGCTTCT
TTTACTTGCACTTGTAAACCAGGTTGGCAAGGAGAAAAGTGTGAATTTGACATAAATGAA
TGCAAAGATCCCTCAAATATAAATGGAGGTTGCAGTCAAATTTGTGATAATACACCTGGA
AGTTACCACTGTTCCTGTAAAAATGGTTTTGTTATGCTTTCAAATAAGAAAGATTGTAAA
GATGTGGATGAATGCTCTTTGAAGCCAAGCATTTGTGGCACAGCTGTGTGCAAGAACATC
CCAGGAGATTTTGAATGTGAATGCCCCGAAGGCTACAGATATAATCTCAAATCAAAGTCT
TGTGAAGATATAGATGAATGCTCTGAGAACATGTGTGCTCAGCTTTGTGTCAATTACCCT
GGAGGTTACACTTGCTATTGTGATGGGAAGAAAGGATTCAAACTTGCCCAAGATCAGAAG
AGTTGTGAGGTTGTTTCAGTGTGCCTTCCCTTGAACCTTGACACAAAGTATGAATTACTT
TACTTGGCGGAGCAGTTTGCAGGGGTTGTTTTATATTTAAAATTTCGTTTGCCAGAAATC
AGCAGATTTTCAGCAGAATTTGATTTCCGGACATATGATTCAGAAGGCGTGATACTGTAC
GCAGAATCTATCGATCACTCAGCGTGGCTCCTGATTGCACTTCGTGGTGGAAAGATTGAA
GTTCAGCTTAAGAATGAACATACATCCAAAATCACAACTGGAGGTGATGTTATTAATAAT
GGTCTATGGAATATGGTGTCTGTGGAAGAATTAGAACATAGTATTAGCATTAAAATAGCT
AAAGAAGCTGTGATGGATATAAATAAACCTGGACCCCTTTTTAAGCCGGAAAATGGATTG
CTGGAAACCAAAGTATACTTTGCAGGATTCCCTCGGAAAGTGGAAAGTGAACTCATTAAA
CCGATTAACCCTCGTCTAGATGGATGTATACGAAGCTGGAATTTGATGAAGCAAGGAGCT
TCTGGAATAAAGGAAATTATTCAAGAAAAACAAAATAAGCATTGCCTGGTTACTGTGGAG
AAGGGCTCCTACTATCCTGGTTCTGGAATTGCTCAATTTCACATAGATTATAATAATGTA
TCCAGTGCTGAGGGTTGGCATGTAAATGTGACCTTGAATATTCGTCCATCCACGGGCACT
GGTGTTATGCTTGCCTTGGTTTCTGGTAACAACACAGTGCCCTTTGCTGTGTCCTTGGTG
GACTCCACCTCTGAAAAATCACAGGATATTCTGTTATCTGTTGAAAATACTGTAATATAT
CGGATACAGGCCCTAAGTCTATGTTCCGATCAACAATCTCATCTGGAATTTAGAGTCAAC
AGAAACAATCTGGAGTTGTCGACACCACTTAAAATAGAAACCATCTCCCATGAAGACCTT
CAAAGACAACTTGCCGTCTTGGACAAAGCAATGAAAGCAAAAGTGGCCACATACCTGGGT
GGCCTTCCAGATGTTCCATTCAGTGCCACACCAGTGAATGCCTTTTATAATGGCTGCATG
GAAGTGAATATTAATGGTGTACAGTTGGATCTGGATGAAGCCATTTCTAAACATAATGAT
ATTAGAGCTCACTCATGTCCATCAGTTTGGAAAAAGACAAAGAATTCTTAA

1. Espinosa-Parrilla Y, Morell M, Souto JC, Tirado I, Fontcuberta J, Estivill X, Sala N: Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency. Hum Mutat. 1999;14(1):30-9. [PubMed ]
2. Bertina RM, Ploos van Amstel HK, van Wijngaarden A, Coenen J, Leemhuis MP, Deutz-Terlouw PP, van der Linden IK, Reitsma PH: Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460. Blood. 1990 Aug 1;76(3):538-48. [PubMed ]
3. Schmidel DK, Tatro AV, Phelps LG, Tomczak JA, Long GL: Organization of the human protein S genes. Biochemistry. 1990 Aug 28;29(34):7845-52. [PubMed ]
4. Ploos van Amstel HK, Reitsma PH, van der Logt CP, Bertina RM: Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution. Biochemistry. 1990 Aug 28;29(34):7853-61. [PubMed ]
5. Ploos van Amstel HK, van der Zanden AL, Reitsma PH, Bertina RM: Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for the post-translational processing. FEBS Lett. 1987 Sep 28;222(1):186-90. [PubMed ]
6. Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlback B, Stenflo J, Wydro R: Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6716-20. [PubMed ]
7. Hoskins J, Norman DK, Beckmann RJ, Long GL: Cloning and characterization of human liver cDNA encoding a protein S precursor. Proc Natl Acad Sci U S A. 1987 Jan;84(2):349-53. [PubMed ]
8. Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K: Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood. 1994 Feb 1;83(3):683-90. [PubMed ]

1. Siegert G, Kostka H, Gehrisch S, Schwarz T, Schellong S, Jaross W: Method-dependent influence of certain polymorphisms in the factor V B-domain on the response to activated protein C. Blood Coagul Fibrinolysis. 2000 Sep;11(6):519-27. [PubMed ]

1. Calnexin precursor
2. IP90
3. Major histocompatibility complex class I antigen- binding protein p88
4. p90

MEGKWLLCMLLVLGTAIVEAHDGHDDDVIDIEDDLDDVIEEVEDSKPDTTAPPSSPKVTY
KAPVPTGEVYFADSFDRGTLSGWILSKAKKDDTDDEIAKYDGKWEVEEMKESKLPGDKGL
VLMSRAKHHAISAKLNKPFLFDTKPLIVQYEVNFQNGIECGGAYVKLLSKTPELNLDQFH
DKTPYTIMFGPDKCGEDYKLHFIFRHKNPKTGIYEEKHAKRPDADLKTYFTDKKTHLYTL
ILNPDNSFEILVDQSVVNSGNLLNDMTPPVNPSREIEDPEDRKPEDWDERPKIPDPEAVK
PDDWDEDAPAKIPDEEATKPEGWLDDEPEYVPDPDAEKPEDWDEDMDGEWEAPQIANPRC
ESAPGCGVWQRPVIDNPNYKGKWKPPMIDNPSYQGIWKPRKIPNPDFFEDLEPFRMTPFS
AIGLELWSMTSDIFFDNFIICADRRIVDDWANDGWGLKKAADGAAEPGVVGQMIEAAEER
PWLWVVYILTVALPVFLVILFCCSGKKQTSGMEYKKTDAPQPDVKEEEEEKEEEKDKGDE
EEEGEEKLEEKQKSDAEEDGGTVSQEEEDRKPKAEEDEILNRSPRNRKPRRE

• Calreticulin (PF00262 )

• 1-20

• 482-502

• Endoplasmic reticulum
• endoplasmic reticulum membrane
• single-pass type I membrane protein. Melanoso

ATGGAAGGGAAGTGGTTGCTGTGTATGTTACTGGTGCTTGGAACTGCTATTGTTGAGGCT
CATGATGGACATGATGATGATGTGATTGATATTGAGGATGACCTTGACGATGTCATTGAA
GAGGTAGAAGACTCAAAACCAGATACCACTGCTCCTCCTTCATCTCCCAAGGTTACTTAC
AAAGCTCCAGTTCCAACAGGGGAAGTATATTTTGCTGATTCTTTTGACAGAGGAACTCTG
TCAGGGTGGATTTTATCCAAAGCCAAGAAAGACGATACCGATGATGAAATTGCCAAATAT
GATGGAAAGTGGGAGGTAGAGGAAATGAAGGAGTCAAAGCTTCCAGGTGATAAAGGACTT
GTGTTGATGTCTCGGGCCAAGCATCATGCGATCTCTGCTAAACTGAACAAGCCCTTCCTG
TTTGACACCAAGCCTCTCATTGTTCAGTATGAGGTTAATTTCCAAAATGGAATAGAATGT
GGTGGTGCCTATGTGAAACTGCTTTCTAAAACACCAGAACTCAACCTGGATCAGTTCCAT
GACAAGACCCCTTATACGATTATGTTTGGTCCAGATAAATGTGGAGAGGACTATAAACTG
CACTTCATCTTCCGACACAAAAACCCCAAAACGGGTATCTATGAAGAAAAACATGCTAAG
AGGCCAGATGCAGATCTGAAGACCTATTTTACTGATAAGAAAACACATCTTTACACACTA
ATCTTGAATCCAGATAATAGTTTTGAAATACTGGTTGACCAATCTGTGGTGAATAGTGGA
AATCTGCTCAATGACATGACTCCTCCTGTAAATCCTTCACGTGAAATTGAGGACCCAGAA
GACCGGAAGCCCGAGGATTGGGATGAAAGACCAAAAATCCCAGATCCAGAAGCTGTCAAG
CCAGATGACTGGGATGAAGATGCCCCTGCTAAGATTCCAGATGAAGAGGCCACAAAACCC
GAAGGCTGGTTAGATGATGAGCCTGAGTACGTACCTGATCCAGACGCAGAGAAACCTGAG
GATTGGGATGAAGACATGGATGGAGAATGGGAGGCTCCTCAGATTGCCAACCCTAGATGT
GAGTCAGCTCCTGGATGTGGTGTCTGGCAGCGACCTGTGATTGACAACCCCAATTATAAA
GGCAAATGGAAGCCTCCTATGATTGACAATCCCAGTTACCAGGGAATCTGGAAACCCAGG
AAAATACCAAATCCAGATTTCTTTGAAGATCTGGAACCTTTCAGAATGACTCCTTTTAGT
GCTATTGGTTTGGAGCTGTGGTCCATGACCTCTGACATTTTTTTTGACAACTTTATCATT
TGTGCTGATCGAAGAATAGTTGATGATTGGGCCAATGATGGATGGGGCCTGAAGAAAGCT
GCTGATGGGGCTGCTGAGCCAGGCGTTGTGGGGCAGATGATCGAGGCAGCTGAAGAGCGC
CCGTGGCTGTGGGTAGTCTATATTCTAACTGTAGCCCTTCCTGTGTTCCTGGTTATCCTC
TTCTGCTGTTCTGGAAAGAAACAGACCAGTGGTATGGAGTATAAGAAAACTGATGCACCT
CAACCGGATGTGAAGGAAGAGGAAGAAGAGAAGGAAGAGGAAAAGGACAAGGGAGATGAG
GAGGAGGAAGGAGAAGAGAAACTTGAAGAGAAACAGAAAAGTGATGCTGAAGAAGATGGT
GGCACTGTCAGTCAAGAGGAGGAAGACAGAAAACCTAAAGCAGAGGAGGATGAAATTTTG
AACAGATCACCAAGAAACAGAAAGCCACGAAGAGAGTGA

1. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. Electrophoresis. 1992 Dec;13(12):960-9. [PubMed ]
2. Galvin K, Krishna S, Ponchel F, Frohlich M, Cummings DE, Carlson R, Wands JR, Isselbacher KJ, Pillai S, Ozturk M: The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8452-6. [PubMed ]
3. Honore B, Rasmussen HH, Celis A, Leffers H, Madsen P, Celis JE: The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin exhibit strikingly different levels in quiescent keratinocytes as compared to their proliferating normal and transformed counterparts: cDNA cloning and expression of calnexin. Electrophoresis. 1994 Mar-Apr;15(3-4):482-90. [PubMed ]
4. Tjoelker LW, Seyfried CE, Eddy RL Jr, Byers MG, Shows TB, Calderon J, Schreiber RB, Gray PW: Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5. Biochemistry. 1994 Mar 22;33(11):3229-36. [PubMed ]
5. David V, Hochstenbach F, Rajagopalan S, Brenner MB: Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin). J Biol Chem. 1993 May 5;268(13):9585-92. [PubMed ]

1. Becker S, Simpson JC, Pepperkok R, Heinz S, Herder C, Grez M, Seifried E, Tonn T: Confocal microscopy analysis of native, full length and B-domain deleted coagulation factor VIII trafficking in mammalian cells. Thromb Haemost. 2004 Jul;92(1):23-35. [PubMed ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
3. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]
4. Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2007 Sep 26;. [PubMed ]
5. Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. [PubMed ]

1. vWF
2. von Willebrand factor precursor

MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYL
LAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYL
ETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTL
TSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPL
VDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGME
YRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPG
TSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQD
HSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDL
RIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSG
LAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVS
PLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQ
CGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPED
IFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADN
LRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGE
TVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGS
NPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGR
YIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVD
FGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPY
LDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGY
ECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCE
VAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVE
DISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVE
YHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRI
ALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVL
SSVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVA
FVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGD
ILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLP
GDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTL
SPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITT
IDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILV
TDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTM
VTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCD
RGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNK
EQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEV
NVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRD
GTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFY
AICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHC
DGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQI
CTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHC
ERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVN
STVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAV
MGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQ
WASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERME
ACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGEC
CGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHK
CLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMY
SIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK

• VWA (PF00092 )
• VWC (PF00093 )
• VWD (PF00094 )
• TIL (PF01826 )
• DUF1787 (PF08742 )

• 1-22

• None

• Secreted protein. Note=Localized to storage granules

ATGATTCCTGCCAGATTTGCCGGGGTGCTGCTTGCTCTGGCCCTCATTTTGCCAGGGACC
CTTTGTGCAGAAGGAACTCGCGGCAGGTCATCCACGGCCCGATGCAGCCTTTTCGGAAGT
GACTTCGTCAACACCTTTGATGGGAGCATGTACAGCTTTGCGGGATACTGCAGTTACCTC
CTGGCAGGGGGCTGCCAGAAACGCTCCTTCTCGATTATTGGGGACTTCCAGAATGGCAAG
AGAGTGAGCCTCTCCGTGTATCTTGGGGAATTTTTTGACATCCATTTGTTTGTCAATGGT
ACCGTGACACAGGGGGACCAAAGAGTCTCCATGCCCTATGCCTCCAAAGGGCTGTATCTA
GAAACTGAGGCTGGGTACTACAAGCTGTCCGGTGAGGCCTATGGCTTTGTGGCCAGGATC
GATGGCAGCGGCAACTTTCAAGTCCTGCTGTCAGACAGATACTTCAACAAGACCTGCGGG
CTGTGTGGCAACTTTAACATCTTTGCTGAAGATGACTTTATGACCCAAGAAGGGACCTTG
ACCTCGGACCCTTATGACTTTGCCAACTCATGGGCTCTGAGCAGTGGAGAACAGTGGTGT
GAACGGGCATCTCCTCCCAGCAGCTCATGCAACATCTCCTCTGGGGAAATGCAGAAGGGC
CTGTGGGAGCAGTGCCAGCTTCTGAAGAGCACCTCGGTGTTTGCCCGCTGCCACCCTCTG
GTGGACCCCGAGCCTTTTGTGGCCCTGTGTGAGAAGACTTTGTGTGAGTGTGCTGGGGGG
CTGGAGTGCGCCTGCCCTGCCCTCCTGGAGTACGCCCGGACCTGTGCCCAGGAGGGAATG
GTGCTGTACGGCTGGACCGACCACAGCGCGTGCAGCCCAGTGTGCCCTGCTGGTATGGAG
TATAGGCAGTGTGTGTCCCCTTGCGCCAGGACCTGCCAGAGCCTGCACATCAATGAAATG
TGTCAGGAGCGATGCGTGGATGGCTGCAGCTGCCCTGAGGGACAGCTCCTGGATGAAGGC
CTCTGCGTGGAGAGCACCGAGTGTCCCTGCGTGCATTCCGGAAAGCGCTACCCTCCCGGC
ACCTCCCTCTCTCGAGACTGCAACACCTGCATTTGCCGAAACAGCCAGTGGATCTGCAGC
AATGAAGAATGTCCAGGGGAGTGCCTTGTCACAGGTCAATCACACTTCAAGAGCTTTGAC
AACAGATACTTCACCTTCAGTGGGATCTGCCAGTACCTGCTGGCCCGGGATTGCCAGGAC
CACTCCTTCTCCATTGTCATTGAGACTGTCCAGTGTGCTGATGACCGCGACGCTGTGTGC
ACCCGCTCCGTCACCGTCCGGCTGCCTGGCCTGCACAACAGCCTTGTGAAACTGAAGCAT
GGGGCAGGAGTTGCCATGGATGGCCAGGACGTCCAGCTCCCCCTCCTGAAAGGTGACCTC
CGCATCCAGCATACAGTGACGGCCTCCGTGCGCCTCAGCTACGGGGAGGACCTGCAGATG
GACTGGGATGGCCGCGGGAGGCTGCTGGTGAAGCTGTCCCCCGTCTATGCCGGGAAGACC
TGCGGCCTGTGTGGGAATTACAATGGCAACCAGGGCGACGACTTCCTTACCCCCTCTGGG
CTGGCGGAGCCCCGGGTGGAGGACTTCGGGAACGCCTGGAAGCTGCACGGGGACTGCCAG
GACCTGCAGAAGCAGCACAGCGATCCCTGCGCCCTCAACCCGCGCATGACCAGGTTCTCC
GAGGAGGCGTGCGCGGTCCTGACGTCCCCCACATTCGAGGCCTGCCATCGTGCCGTCAGC
CCGCTGCCCTACCTGCGGAACTGCCGCTACGACGTGTGCTCCTGCTCGGACGGCCGCGAG
TGCCTGTGCGGCGCCCTGGCCAGCTATGCCGCGGCCTGCGCGGGGAGAGGCGTGCGCGTC
GCGTGGCGCGAGCCAGGCCGCTGTGAGCTGAACTGCCCGAAAGGCCAGGTGTACCTGCAG
TGCGGGACCCCCTGCAACCTGACCTGCCGCTCTCTCTCTTACCCGGATGAGGAATGCAAT
GAGGCCTGCCTGGAGGGCTGCTTCTGCCCCCCAGGGCTCTACATGGATGAGAGGGGGGAC
TGCGTGCCCAAGGCCCAGTGCCCCTGTTACTATGACGGTGAGATCTTCCAGCCAGAAGAC
ATCTTCTCAGACCATCACACCATGTGCTACTGTGAGGATGGCTTCATGCACTGTACCATG
AGTGGAGTCCCCGGAAGCTTGCTGCCTGACGCTGTCCTCAGCAGTCCCCTGTCTCATCGC
AGCAAAAGGAGCCTATCCTGTCGGCCCCCCATGGTCAAGCTGGTGTGTCCCGCTGACAAC
CTGCGGGCTGAAGGGCTCGAGTGTACCAAAACGTGCCAGAACTATGACCTGGAGTGCATG
AGCATGGGCTGTGTCTCTGGCTGCCTCTGCCCCCCGGGCATGGTCCGGCATGAGAACAGA
TGTGTGGCCCTGGAAAGGTGTCCCTGCTTCCATCAGGGCAAGGAGTATGCCCCTGGAGAA
ACAGTGAAGATTGGCTGCAACACTTGTGTCTGTCGGGACCGGAAGTGGAACTGCACAGAC
CATGTGTGTGATGCCACGTGCTCCACGATCGGCATGGCCCACTACCTCACCTTCGACGGG
CTCAAATACCTGTTCCCCGGGGAGTGCCAGTACGTTCTGGTGCAGGATTACTGCGGCAGT
AACCCTGGGACCTTTCGGATCCTAGTGGGGAATAAGGGATGCAGCCACCCCTCAGTGAAA
TGCAAGAAACGGGTCACCATCCTGGTGGAGGGAGGAGAGATTGAGCTGTTTGACGGGGAG
GTGAATGTGAAGAGGCCCATGAAGGATGAGACTCACTTTGAGGTGGTGGAGTCTGGCCGG
TACATCATTCTGCTGCTGGGCAAAGCCCTCTCCGTGGTCTGGGACCGCCACCTGAGCATC
TCCGTGGTCCTGAAGCAGACATACCAGGAGAAAGTGTGTGGCCTGTGTGGGAATTTTGAT
GGCATCCAGAACAATGACCTCACCAGCAGCAACCTCCAAGTGGAGGAAGACCCTGTGGAC
TTTGGGAACTCCTGGAAAGTGAGCTCGCAGTGTGCTGACACCAGAAAAGTGCCTCTGGAC
TCATCCCCTGCCACCTGCCATAACAACATCATGAAGCAGACGATGGTGGATTCCTCCTGT
AGAATCCTTACCAGTGACGTCTTCCAGGACTGCAACAAGCTGGTGGACCCCGAGCCATAT
CTGGATGTCTGCATTTACGACACCTGCTCCTGTGAGTCCATTGGGGACTGCGCCTGCTTC
TGCGACACCATTGCTGCCTATGCCCACGTGTGTGCCCAGCATGGCAAGGTGGTGACCTGG
AGGACGGCCACATTGTGCCCCCAGAGCTGCGAGGAGAGGAATCTCCGGGAGAACGGGTAT
GAGTGTGAGTGGCGCTATAACAGCTGTGCACCTGCCTGTCAAGTCACGTGTCAGCACCCT
GAGCCACTGGCCTGCCCTGTGCAGTGTGTGGAGGGCTGCCATGCCCACTGCCCTCCAGGG
AAAATCCTGGATGAGCTTTTGCAGACCTGCGTTGACCCTGAAGACTGTCCAGTGTGTGAG
GTGGCTGGCCGGCGTTTTGCCTCAGGAAAGAAAGTCACCTTGAATCCCAGTGACCCTGAG
CACTGCCAGATTTGCCACTGTGATGTTGTCAACCTCACCTGTGAAGCCTGCCAGGAGCCG
GGAGGCCTGGTGGTGCCTCCCACAGATGCCCCGGTGAGCCCCACCACTCTGTATGTGGAG
GACATCTCGGAACCGCCGTTGCACGATTTCTACTGCAGCAGGCTACTGGACCTGGTCTTC
CTGCTGGATGGCTCCTCCAGGCTGTCCGAGGCTGAGTTTGAAGTGCTGAAGGCCTTTGTG
GTGGACATGATGGAGCGGCTGCGCATCTCCCAGAAGTGGGTCCGCGTGGCCGTGGTGGAG
TACCACGACGGCTCCCACGCCTACATCGGGCTCAAGGACCGGAAGCGACCGTCAGAGCTG
CGGCGCATTGCCAGCCAGGTGAAGTATGCGGGCAGCCAGGTGGCCTCCACCAGCGAGGTC
TTGAAATACACACTGTTCCAAATCTTCAGCAAGATCGACCGCCCTGAAGCCTCCCGCATC
GCCCTGCTCCTGATGGCCAGCCAGGAGCCCCAACGGATGTCCCGGAACTTTGTCCGCTAC
GTCCAGGGCCTGAAGAAGAAGAAGGTCATTGTGATCCCGGTGGGCATTGGGCCCCATGCC
AACCTCAAGCAGATCCGCCTCATCGAGAAGCAGGCCCCTGAGAACAAGGCCTTCGTGCTG
AGCAGTGTGGATGAGCTGGAGCAGCAAAGGGACGAGATCGTTAGCTACCTCTGTGACCTT
GCCCCTGAAGCCCCTCCTCCTACTCTGCCCCCCCACATGGCACAAGTCACTGTGGGCCCG
GGGCTCTTGGGGGTTTCGACCCTGGGGCCCAAGAGGAACTCCATGGTTCTGGATGTGGCG
TTCGTCCTGGAAGGATCGGACAAAATTGGTGAAGCCGACTTCAACAGGAGCAAGGAGTTC
ATGGAGGAGGTGATTCAGCGGATGGATGTGGGCCAGGACAGCATCCACGTCACGGTGCTG
CAGTACTCCTACATGGTGACCGTGGAGTACCCCTTCAGCGAGGCACAGTCCAAAGGGGAC
ATCCTGCAGCGGGTGCGAGAGATCCGCTACCAGGGCGGCAACAGGACCAACACTGGGCTG
GCCCTGCGGTACCTCTCTGACCACAGCTTCTTGGTCAGCCAGGGTGACCGGGAGCAGGCG
CCCAACCTGGTCTACATGGTCACCGGAAATCCTGCCTCTGATGAGATCAAGAGGCTGCCT
GGAGACATCCAGGTGGTGCCCATTGGAGTGGGCCCTAATGCCAACGTGCAGGAGCTGGAG
AGGATTGGCTGGCCCAATGCCCCTATCCTCATCCAGGACTTTGAGACGCTCCCCCGAGAG
GCTCCTGACCTGGTGCTGCAGAGGTGCTGCTCCGGAGAGGGGCTGCAGATCCCCACCCTC
TCCCCTGCACCTGACTGCAGCCAGCCCCTGGACGTGATCCTTCTCCTGGATGGCTCCTCC
AGTTTCCCAGCTTCTTATTTTGATGAAATGAAGAGTTTCGCCAAGGCTTTCATTTCAAAA
GCCAATATAGGGCCTCGTCTCACTCAGGTGTCAGTGCTGCAGTATGGAAGCATCACCACC
ATTGACGTGCCATGGAACGTGGTCCCGGAGAAAGCCCATTTGCTGAGCCTTGTGGACGTC
ATGCAGCGGGAGGGAGGCCCCAGCCAAATCGGGGATGCCTTGGGCTTTGCTGTGCGATAC
TTGACTTCAGAAATGCATGGTGCCAGGCCGGGAGCCTCAAAGGCGGTGGTCATCCTGGTC
ACGGACGTCTCTGTGGATTCAGTGGATGCAGCAGCTGATGCCGCCAGGTCCAACAGAGTG
ACAGTGTTCCCTATTGGAATTGGAGATCGCTACGATGCAGCCCAGCTACGGATCTTGGCA
GGCCCAGCAGGCGACTCCAACGTGGTGAAGCTCCAGCGAATCGAAGACCTCCCTACCATG
GTCACCTTGGGCAATTCCTTCCTCCACAAACTGTGCTCTGGATTTGTTAGGATTTGCATG
GATGAGGATGGGAATGAGAAGAGGCCCGGGGACGTCTGGACCTTGCCAGACCAGTGCCAC
ACCGTGACTTGCCAGCCAGATGGCCAGACCTTGCTGAAGACTCATCGGGTCAACTGTGAC
CGGGGGCTGAGGCCTTCGTGCCCTAACAGCCAGTCCCCTGTTAAAGTGGAAGAGACCTGT
GGCTGCCGCTGGACCTGCCCCTGCGTGTGCACAGGCAGCTCCACTCGGCACATCGTGACC
TTTGATGGGCAGAATTTCAAGCTGACTGGCAGCTGTTCTTATGTCCTATTTCAAAACAAG
GAGCAGGACCTGGAGGTGATTCTCCATAATGGTGCCTGCAGCCCTGGAGCAAGGCAGGGC
TGCATGAAATCCATCGAGGTGAAGCACAGTGCCCTCTCCGTCGAGCTGCACAGTGACATG
GAGGTGACGGTGAATGGGAGACTGGTCTCTGTTCCTTACGTGGGTGGGAACATGGAAGTC
AACGTTTATGGTGCCATCATGCATGAGGTCAGATTCAATCACCTTGGTCACATCTTCACA
TTCACTCCACAAAACAATGAGTTCCAACTGCAGCTCAGCCCCAAGACTTTTGCTTCAAAG
ACGTATGGTCTGTGTGGGATCTGTGATGAGAACGGAGCCAATGACTTCATGCTGAGGGAT
GGCACAGTCACCACAGACTGGAAAACACTTGTTCAGGAATGGACTGTGCAGCGGCCAGGG
CAGACGTGCCAGCCCATCCTGGAGGAGCAGTGTCTTGTCCCCGACAGCTCCCACTGCCAG
GTCCTCCTCTTACCACTGTTTGCTGAATGCCACAAGGTCCTGGCTCCAGCCACATTCTAT
GCCATCTGCCAGCAGGACAGTTGCCACCAGGAGCAAGTGTGTGAGGTGATCGCCTCTTAT
GCCCACCTCTGTCGGACCAACGGGGTCTGCGTTGACTGGAGGACACCTGATTTCTGTGCT
ATGTCATGCCCACCATCTCTGGTCTACAACCACTGTGAGCATGGCTGTCCCCGGCACTGT
GATGGCAACGTGAGCTCCTGTGGGGACCATCCCTCCGAAGGCTGTTTCTGCCCTCCAGAT
AAAGTCATGTTGGAAGGCAGCTGTGTCCCTGAAGAGGCCTGCACTCAGTGCATTGGTGAG
GATGGAGTCCAGCACCAGTTCCTGGAAGCCTGGGTCCCGGACCACCAGCCCTGTCAGATC
TGCACATGCCTCAGCGGGCGGAAGGTCAACTGCACAACGCAGCCCTGCCCCACGGCCAAA
GCTCCCACGTGTGGCCTGTGTGAAGTAGCCCGCCTCCGCCAGAATGCAGACCAGTGCTGC
CCCGAGTATGAGTGTGTGTGTGACCCAGTGAGCTGTGACCTGCCCCCAGTGCCTCACTGT
GAACGTGGCCTCCAGCCCACACTGACCAACCCTGGCGAGTGCAGACCCAACTTCACCTGC
GCCTGCAGGAAGGAGGAGTGCAAAAGAGTGTCCCCACCCTCCTGCCCCCCGCACCGTTTG
CCCACCCTTCGGAAGACCCAGTGCTGTGATGAGTATGAGTGTGCCTGCAACTGTGTCAAC
TCCACAGTGAGCTGTCCCCTTGGGTACTTGGCCTCAACCGCCACCAATGACTGTGGCTGT
ACCACAACCACCTGCCTTCCCGACAAGGTGTGTGTCCACCGAAGCACCATCTACCCTGTG
GGCCAGTTCTGGGAGGAGGGCTGCGATGTGTGCACCTGCACCGACATGGAGGATGCCGTG
ATGGGCCTCCGCGTGGCCCAGTGCTCCCAGAAGCCCTGTGAGGACAGCTGTCGGTCGGGC
TTCACTTACGTTCTGCATGAAGGCGAGTGCTGTGGAAGGTGCCTGCCATCTGCCTGTGAG
GTGGTGACTGGCTCACCGCGGGGGGACTCCCAGTCTTCCTGGAAGAGTGTCGGCTCCCAG
TGGGCCTCCCCGGAGAACCCCTGCCTCATCAATGAGTGTGTCCGAGTGAAGGAGGAGGTC
TTTATACAACAAAGGAACGTCTCCTGCCCCCAGCTGGAGGTCCCTGTCTGCCCCTCGGGC
TTTCAGCTGAGCTGTAAGACCTCAGCGTGCTGCCCAAGCTGTCGCTGTGAGCGCATGGAG
GCCTGCATGCTCAATGGCACTGTCATTGGGCCCGGGAAGACTGTGATGATCGATGTGTGC
ACGACCTGCCGCTGCATGGTGCAGGTGGGGGTCATCTCTGGATTCAAGCTGGAGTGCAGG
AAGACCACCTGCAACCCCTGCCCCCTGGGTTACAAGGAAGAAAATAACACAGGTGAATGT
TGTGGGAGATGTTTGCCTACGGCTTGCACCATTCAGCTAAGAGGAGGACAGATCATGACA
CTGAAGCGTGATGAGACGCTCCAGGATGGCTGTGATACTCACTTCTGCAAGGTCAATGAG
AGAGGAGAGTACTTCTGGGAGAAGAGGGTCACAGGCTGCCCACCCTTTGATGAACACAAG
TGTCTGGCTGAGGGAGGTAAAATTATGAAAATTCCAGGCACCTGCTGTGACACATGTGAG
GAGCCTGAGTGCAACGACATCACTGCCAGGCTGCAGTATGTCAAGGTGGGAAGCTGTAAG
TCTGAAGTAGAGGTGGATATCCACTACTGCCAGGGCAAATGTGCCAGCAAAGCCATGTAC
TCCATTGACATCAACGATGTGCAGGACCAGTGCTCCTGCTGCTCTCCGACACGGACGGAG
CCCATGCAGGTGGCCCTGCACTGCACCAATGGCTCTGTTGTGTACCATGAGGTTCTCAAT
GCCATGGAGTGCAAATGCTCCCCCAGGAAGTGCAGCAAGTGA

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6. Donner M, Kristoffersson AC, Lenk H, Scheibel E, Dahlback B, Nilsson IM, Holmberg L: Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden. Br J Haematol. 1992 Sep;82(1):58-65. [PubMed ]
7. Lavergne JM, De Paillette L, Bahnak BR, Ribba AS, Fressinaud E, Meyer D, Pietu G: Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX. Br J Haematol. 1992 Sep;82(1):66-72. [PubMed ]
8. Pietu G, Ribba AS, de Paillette L, Cherel G, Lavergne JM, Bahnak BR, Meyer D: Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB. Blood Coagul Fibrinolysis. 1992 Aug;3(4):415-21. [PubMed ]
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12. 1729889 Murray EW, Giles AR, Lillicrap D: Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease. Am J Hum Genet. 1992 Jan;50(1):199-207.
13. 1761120 Donner M, Andersson AM, Kristoffersson AC, Nilsson IM, Dahlback B, Holmberg L: An Arg545----Cys545 substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease. Eur J Haematol. 1991 Nov;47(5):342-5.
14. 1832934 Gaucher C, Mercier B, Jorieux S, Oufkir D, Mazurier C: Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease. Br J Haematol. 1991 Aug;78(4):506-14.
15. 1906179 Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C: Expression of von Willebrand factor "Normandy": an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6377-81.
16. 1988024 Mancuso DJ, Tuley EA, Westfield LA, Lester-Mancuso TL, Le Beau MM, Sorace JM, Sadler JE: Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry. 1991 Jan 8;30(1):253-69.
17. 2010538 Randi AM, Rabinowitz I, Mancuso DJ, Mannucci PM, Sadler JE: Molecular basis of von Willebrand disease type IIB. Candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences. J Clin Invest. 1991 Apr;87(4):1220-6.
18. 2011604 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrle PA, Yoshioka A, Ruggeri ZM: Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2946-50.
19. 2584182 Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB, Sorace JM, Alevy YG, Sadler JE: Structure of the gene for human von Willebrand factor. J Biol Chem. 1989 Nov 25;264(33):19514-27.
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21. 2828057 Bonthron D, Orkin SH: The human von Willebrand factor gene. Structure of the 5' region. Eur J Biochem. 1988 Jan 15;171(1-2):51-7.
22. 2864688 Sadler JE, Shelton-Inloes BB, Sorace JM, Harlan JM, Titani K, Davie EW: Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6394-8.
23. 3019665 Verweij CL, Diergaarde PJ, Hart M, Pannekoek H: Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein considerably larger than the mature vWF subunit. EMBO J. 1986 Aug;5(8):1839-47.
24. 3089784 Samor B, Michalski JC, Debray H, Mazurier C, Goudemand M, Van Halbeek H, Vliegenthart JF, Montreuil J: Primary structure of a new tetraantennary glycan of the N-acetyllactosaminic type isolated from human factor VIII/von Willebrand factor. Eur J Biochem. 1986 Jul 15;158(2):295-8.
25. 3488076 Shelton-Inloes BB, Titani K, Sadler JE: cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms. Biochemistry. 1986 Jun 3;25(11):3164-71.
26. 3489923 Bonthron D, Orr EC, Mitsock LM, Ginsburg D, Handin RI, Orkin SH: Nucleotide sequence of pre-pro-von Willebrand factor cDNA. Nucleic Acids Res. 1986 Sep 11;14(17):7125-7.
27. 3495266 Shelton-Inloes BB, Broze GJ Jr, Miletich JP, Sadler JE: Evolution of human von Willebrand factor: cDNA sequence polymorphisms, repeated domains, and relationship to von Willebrand antigen II. Biochem Biophys Res Commun. 1987 Apr 29;144(2):657-65.
28. 3496594 Collins CJ, Underdahl JP, Levene RB, Ravera CP, Morin MJ, Dombalagian MJ, Ricca G, Livingston DM, Lynch DC: Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4393-7.
29. 3502076 Marti T, Rosselet SJ, Titani K, Walsh KA: Identification of disulfide-bridged substructures within human von Willebrand factor. Biochemistry. 1987 Dec 15;26(25):8099-109.
30. 3524673 Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Chopek MW, Sadler JE, Fujikawa K: Amino acid sequence of human von Willebrand factor. Biochemistry. 1986 Jun 3;25(11):3171-84.
31. 3873280 Lynch DC, Zimmerman TS, Collins CJ, Brown M, Morin MJ, Ling EH, Livingston DM: Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell. 1985 May;41(1):49-56.
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33. 3875078 Verweij CL, de Vries CJ, Distel B, van Zonneveld AJ, van Kessel AG, van Mourik JA, Pannekoek H: Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene. Nucleic Acids Res. 1985 Jul 11;13(13):4699-717.
34. 7620154 Hilbert L, Gaucher C, Mazurier C: Identification of two mutations (Arg611Cys and Arg611His) in the A1 loop of von Willebrand factor (vWF) responsible for type 2 von Willebrand disease with decreased platelet-dependent function of vWF. Blood. 1995 Aug 1;86(3):1010-8.
35. 7734373 Castaman G, Eikenboom JC, Rodeghiero F, Briet E, Reitsma PH: A novel candidate mutation (Arg611-->His) in type I 'platelet discordant' von Willebrand's disease with desmopressin-induced thrombocytopenia. Br J Haematol. 1995 Mar;89(3):656-8.
36. 7789955 Schneppenheim R, Thomas KB, Krey S, Budde U, Jessat U, Sutor AH, Zieger B: Identification of a candidate missense mutation in a family with von Willebrand disease type IIC. Hum Genet. 1995 Jun;95(6):681-6.
37. 7989040 Schneppenheim R, Krey S, Bergmann F, Bock D, Budde U, Lange M, Linde R, Mittler U, Meili E, Mertes G, et al.: Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet. 1994 Dec;94(6):640-52.
38. 8011991 Uno H, Nishida N, Ishizaki J, Suzuki M, Nishikubo T, Miyata S, Takahashi Y, Yoshioka A, Tsuda K: Investigation of type IIC von Willebrand disease. Int J Hematol. 1994 Apr;59(3):219-25.
39. 8088787 Zhang ZP, Blomback M, Egberg N, Falk G, Anvret M: Characterization of the von Willebrand factor gene (VWF) in von Willebrand disease type III patients from 24 families of Swedish and Finnish origin. Genomics. 1994 May 1;21(1):188-93.
40. 8123843 Hilbert L, Gaucher C, de Romeuf C, Horellou MH, Vink T, Mazurier C: Leu 697-->Val mutation in mature von Willebrand factor is responsible for type IIB von Willebrand disease. Blood. 1994 Mar 15;83(6):1542-50.
41. 8123844 Lyons SE, Cooney KA, Bockenstedt P, Ginsburg D: Characterization of Leu777Pro and Ile865Thr type IIA von Willebrand disease mutations. Blood. 1994 Mar 15;83(6):1551-7.
42. 8338947 Inbal A, Englender T, Kornbrot N, Randi AM, Castaman G, Mannucci PM, Sadler JE: Identification of three candidate mutations causing type IIA von Willebrand disease using a rapid, nonradioactive, allele-specific hybridization method. Blood. 1993 Aug 1;82(3):830-6.
43. 8348943 Donner M, Kristoffersson AC, Berntorp E, Scheibel E, Thorsen S, Dahlback B, Nilsson IM, Holmberg L: Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor. Eur J Haematol. 1993 Jul;51(1):38-44.
44. 8376405 Rabinowitz I, Randi AM, Shindler KS, Tuley EA, Rustagi PK, Sadler JE: Type IIB mutation His-505-->Asp implicates a new segment in the control of von Willebrand factor binding to platelet glycoprotein Ib. J Biol Chem. 1993 Sep 25;268(27):20497-501.
45. 8435341 Gaucher C, Hanss M, Dechavanne M, Mazurier C: Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease. Br J Haematol. 1993 Jan;83(1):94-9.
46. 8486782 Holmberg L, Dent JA, Schneppenheim R, Budde U, Ware J, Ruggeri ZM: von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure. J Clin Invest. 1993 May;91(5):2169-77.
47. 8547152 Hilbert L, Gaucher C, Mazurier C: Effects of different amino-acid substitutions in the leucine 694-proline 708 segment of recombinant von Willebrand factor. Br J Haematol. 1995 Dec;91(4):983-90.
48. 8622978 Schneppenheim R, Brassard J, Krey S, Budde U, Kunicki TJ, Holmberg L, Ware J, Ruggeri ZM: Defective dimerization of von Willebrand factor subunits due to a Cys-> Arg mutation in type IID von Willebrand disease. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3581-6.
49. 9312128 Bienkowska J, Cruz M, Atiemo A, Handin R, Liddington R: The von willebrand factor A3 domain does not contain a metal ion-dependent adhesion site motif. J Biol Chem. 1997 Oct 3;272(40):25162-7.
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51. 9553097 Emsley J, Cruz M, Handin R, Liddington R: Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib. J Biol Chem. 1998 Apr 24;273(17):10396-401.

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3. Gill JC, Ewenstein BM, Thompson AR, Mueller-Velten G, Schwartz BA: Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy. Haemophilia. 2003 Nov;9(6):688-95. [PubMed ]
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5. Altieri DC, Capitanio AM, Mannucci PM: von Willebrand factor contaminating porcine factor VIII concentrate (Hyate:C) causes platelet aggregation. Br J Haematol. 1986 Aug;63(4):703-11. [PubMed ]

1. 78 kDa glucose-regulated protein precursor
2. BiP
3. Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78
4. GRP 78
5. Heat shock 70 kDa protein 5
6. Immunoglobulin heavy chain-binding protein

MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNR
ITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVV
EKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQ
RQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNG
VFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS
SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIV
LVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVC
PLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLG
TFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIER
MVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE
KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL

• HSP70 (PF00012 )

• 1-18

• None

• Endoplasmic reticulum
• endoplasmic reticulum lumen. Melanosome. Note=Identified by mass spectrometry

ATGAAGCTCTCCCTGGTGGCCGCGATGCTGCTGCTGCTCAGCGCGGCGCGGGCCGAGGAG
GAGGACAAGAAGGAGGACGTGGGCACGGTGGTCGGCATCGACTTGGGGACCACCTACTCC
TGCGTCGGCGTGTTCAAGAACGGCCGCGTGGAGATCATCGCCAACGATCAGGGCAACCGC
ATCACGCCGTCCTATGTCGCCTTCACTCCTGAAGGGGAACGTCTGATTGGCGATGCCGCC
AAGAACCAGCTCACCTCCAACCCCGAGAACACGGTCTTTGACGCCAAGCGGCTCATCGGC
CGCACGTGGAATGACCCGTCTGTGCAGCAGGACATCAAGTTCTTGCCGTTCAAGGTGGTT
GAAAAGAAAACTAAACCATACATTCAAGTTGATATTGGAGGTGGGCAAACAAAGACATTT
GCTCCTGAAGAAATTTCTGCCATGGTTCTCACTAAAATGAAAGAAACCGCTGAGGCTTAT
TTGGGAAAGAAGGTTACCCATGCAGTTGTTACTGTACCAGCCTATTTTAATGATGCCCAA
CGCCAAGCAACCAAAGACGCTGGAACTATTGCTGGCCTAAATGTTATGAGGATCATCAAC
GAGCCTACGGCAGCTGCTATTGCTTATGGCCTGGATAAGAGGGAGGGGGAGAAGAACATC
CTGGTGTTTGACCTGGGTGGCGGAACCTTCGATGTGTCTCTTCTCACCATTGACAATGGT
GTCTTCGAAGTTGTGGCCACTAATGGAGATACTCATCTGGGTGGAGAAGACTTTGACCAG
CGTGTCATGGAACACTTCATCAAACTGTACAAAAAGAAGACGGGCAAAGATGTCAGGAAG
GACAATAGAGCTGTGCAGAAACTCCGGCGCGAGGTAGAAAAGGCCAAGGCCCTGTCTTCT
CAGCATCAAGCAAGAATTGAAATTGAGTCCTTCTATGAAGGAGAAGACTTTTCTGAGACC
CTGACTCGGGCCAAATTTGAAGAGCTCAACATGGATCTGTTCCGGTCTACTATGAAGCCC
GTCCAGAAAGTGTTGGAAGATTCTGATTTGAAGAAGTCTGATATTGATGAAATTGTTCTT
GTTGGTGGCTCGACTCGAATTCCAAAGATTCAGCAACTGGTTAAAGAGTTCTTCAATGGC
AAGGAACCATCCCGTGGCATAAACCCAGATGAAGCTGTAGCGTATGGTGCTGCTGTCCAG
GCTGGTGTGCTCTCTGGTGATCAAGATACAGGTGACCTGGTACTGCTTCATGTATGTCCC
CTTACACTTGGTATTGAAACTGTAGGAGGTGTCATGACCAAACTGATTCCAAGTAATACA
GTGGTGCCTACCAAGAACTCTCAGATCTTTTCTACAGCTTCTGATAATCAACCAACTGTT
ACAATCAAGGTCTATGAAGGTGAAAGACCCCTGACAAAAGACAATCATCTTCTGGGTACA
TTTGATCTGACTGGAATTCCTCCTGCTCCTCGTGGGGTCCCACAGATTGAAGTCACCTTT
GAGATAGATGTGAATGGTATTCTTCGAGTGACAGCTGAAGACAAGGGTACAGGGAACAAA
AATAAGATCACAATCACCAATGACCAGAATCGCCTGACACCTGAAGAAATCGAAAGGATG
GTTAATGATGCTGAGAAGTTTGCTGAGGAAGACAAAAAGCTGAAGGAGCGCATTGATACT
AGAAATGAGTTGGAAAGCTATGCCTATTCTCTAAAGAATCAGATTGGAGATAAAGAAAAG
CTGGGAGGTAAACTTTCCTCTGAAGATAAGGAGACCATGGAAAAAGCTGTAGAAGAAAAG
ATTGAATGGCTGGAAAGCCACCAAGATGCTGACATTGAAGACTTCAAAGCTAAGAAGAAG
GAACTGGAAGAAATTGTTCAACCAATTATCAGCAAACTCTATGGAAGTGCAGGCCCTCCC
CCAACTGGTGAAGAGGATACAGCAGAAAAAGATGAGTTGTAG

1. Chao CC, Lin-Chao S: A direct-repeat sequence of the human BiP gene is required for A23187-mediated inducibility and an inducible nuclear factor binding. Nucleic Acids Res. 1992 Dec 25;20(24):6481-5. [PubMed ]
2. Dana RC, Welch WJ, Deftos LJ: Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. [PubMed ]
3. Ting J, Lee AS: Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation. DNA. 1988 May;7(4):275-86. [PubMed ]
4. Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS: Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2. Electrophoresis. 1997 Mar-Apr;18(3-4):588-98. [PubMed ]
5. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. CRP55
2. Calregulin
3. Calreticulin precursor
4. ERp60
5. HACBP
6. grp60

MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDE
EKDKGLQTSQDARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQT
DMHGDSEYNIMFGPDICGPGTKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDN
TYEVKIDNSQVESGSLEDDWDFLPPKKIKDPDASKPEDWDERAKIDDPTDSKPEDWDKPE
HIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQIDNPDYKGTWIHPEIDNPEYS
PDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVTKAAEKQMKDK
QDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL

• Calreticulin (PF00262 )

• 1-17

• None

• Endoplasmic reticulum

ATGCTGCTATCCGTGCCGCTGCTGCTCGGCCTCCTCGGCCTGGCCGTCGCCGAGCCCGCC
GTCTACTTCAAGGAGCAGTTTCTGGACGGAGACGGGTGGACTTCCCGCTGGATCGAATCC
AAACACAAGTCAGATTTTGGCAAATTCGTTCTCAGTTCCGGCAAGTTCTACGGTGACGAG
GAGAAAGATAAAGGTTTGCAGACAAGCCAGGATGCACGCTTTTATGCTCTGTCGGCCAGT
TTCGAGCCTTTCAGCAACAAAGGCCAGACGCTGGTGGTGCAGTTCACGGTGAAACATGAG
CAGAACATCGACTGTGGGGGCGGCTATGTGAAGCTGTTTCCTAATAGTTTGGACCAGACA
GACATGCACGGAGACTCAGAATACAACATCATGTTTGGTCCCGACATCTGTGGCCCTGGC
ACCAAGAAGGTTCATGTCATCTTCAACTACAAGGGCAAGAACGTGCTGATCAACAAGGAC
ATCCGTTGCAAGGATGATGAGTTTACACACCTGTACACACTGATTGTGCGGCCAGACAAC
ACCTATGAGGTGAAGATTGACAACAGCCAGGTGGAGTCCGGCTCCTTGGAAGACGATTGG
GACTTCCTGCCACCCAAGAAGATAAAGGATCCTGATGCTTCAAAACCGGAAGACTGGGAT
GAGCGGGCCAAGATCGATGATCCCACAGACTCCAAGCCTGAGGACTGGGACAAGCCCGAG
CATATCCCTGACCCTGATGCTAAGAAGCCCGAGGACTGGGATGAAGAGATGGACGGAGAG
TGGGAACCCCCAGTGATTCAGAACCCTGAGTACAAGGGTGAGTGGAAGCCCCGGCAGATC
GACAACCCAGATTACAAGGGCACTTGGATCCACCCAGAAATTGACAACCCCGAGTATTCT
CCCGATCCCAGTATCTATGCCTATGATAACTTTGGCGTGCTGGGCCTGGACCTCTGGCAG
GTCAAGTCTGGCACCATCTTTGACAACTTCCTCATCACCAACGATGAGGCATACGCTGAG
GAGTTTGGCAACGAGACGTGGGGCGTAACAAAGGCAGCAGAGAAACAAATGAAGGACAAA
CAGGACGAGGAGCAGAGGCTTAAGGAGGAGGAAGAAGACAAGAAACGCAAAGAGGAGGAG
GAGGCAGAGGACAAGGAGGATGATGAGGACAAAGATGAGGATGAGGAGGATGAGGAGGAC
AAGGAGGAAGATGAGGAGGAAGATGTCCCCGGCCAGGCCAAGGACGAGCTGTAG

1. Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R, et al.: Human liver protein map: a reference database established by microsequencing and gel comparison. Electrophoresis. 1992 Dec;13(12):992-1001. [PubMed ]
2. McCauliffe DP, Yang YS, Wilson J, Sontheimer RD, Capra JD: The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters. J Biol Chem. 1992 Feb 5;267(4):2557-62. [PubMed ]
3. Rojiani MV, Finlay BB, Gray V, Dedhar S: In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. Biochemistry. 1991 Oct 15;30(41):9859-66. [PubMed ]
4. Rokeach LA, Haselby JA, Meilof JF, Smeenk RJ, Unnasch TR, Greene BM, Hoch SO: Characterization of the autoantigen calreticulin. J Immunol. 1991 Nov 1;147(9):3031-9. [PubMed ]
5. McCauliffe DP, Lux FA, Lieu TS, Sanz I, Hanke J, Newkirk MM, Bachinski LL, Itoh Y, Siciliano MJ, Reichlin M, et al.: Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen. J Clin Invest. 1990 May;85(5):1379-91. [PubMed ]
6. Krause KH, Simmerman HK, Jones LR, Campbell KP: Sequence similarity of calreticulin with a Ca2(+)-binding protein that co-purifies with an Ins(1,4,5)P3-sensitive Ca2+ store in HL-60 cells. Biochem J. 1990 Sep 1;270(2):545-8. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]
3. Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2007 Sep 26;. [PubMed ]
4. Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. [PubMed ]
5. Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. [PubMed ]

1. A2MR
2. APOER
3. Alpha-2-macroglobulin receptor
4. Apolipoprotein E receptor
5. CD91 antigen
6. LRP
7. Low-density lipoprotein receptor-related protein 1 precursor

MLTPPLLLLLPLLSALVAAAIDAPKTCSPKQFACRDQITCISKGWRCDGERDCPDGSDEA
PEICPQSKAQRCQPNEHNCLGTELCVPMSRLCNGVQDCMDGSDEGPHCRELQGNCSRLGC
QHHCVPTLDGPTCYCNSSFQLQADGKTCKDFDECSVYGTCSQLCTNTDGSFICGCVEGYL
LQPDNRSCKAKNEPVDRPPVLLIANSQNILATYLSGAQVSTITPTSTRQTTAMDFSYANE
TVCWVHVGDSAAQTQLKCARMPGLKGFVDEHTINISLSLHHVEQMAIDWLTGNFYFVDDI
DDRIFVCNRNGDTCVTLLDLELYNPKGIALDPAMGKVFFTDYGQIPKVERCDMDGQNRTK
LVDSKIVFPHGITLDLVSRLVYWADAYLDYIEVVDYEGKGRQTIIQGILIEHLYGLTVFE
NYLYATNSDNANAQQKTSVIRVNRFNSTEYQVVTRVDKGGALHIYHQRRQPRVRSHACEN
DQYGKPGGCSDICLLANSHKARTCRCRSGFSLGSDGKSCKKPEHELFLVYGKGRPGIIRG
MDMGAKVPDEHMIPIENLMNPRALDFHAETGFIYFADTTSYLIGRQKIDGTERETILKDG
IHNVEGVAVDWMGDNLYWTDDGPKKTISVARLEKAAQTRKTLIEGKMTHPRAIVVDPLNG
WMYWTDWEEDPKDSRRGRLERAWMDGSHRDIFVTSKTVLWPNGLSLDIPAGRLYWVDAFY
DRIETILLNGTDRKIVYEGPELNHAFGLCHHGNYLFWTEYRSGSVYRLERGVGGAPPTVT
LLRSERPPIFEIRMYDAQQQQVGTNKCRVNNGGCSSLCLATPGSRQCACAEDQVLDADGV
TCLANPSYVPPPQCQPGEFACANSRCIQERWKCDGDNDCLDNSDEAPALCHQHTCPSDRF
KCENNRCIPNRWLCDGDNDCGNSEDESNATCSARTCPPNQFSCASGRCIPISWTCDLDDD
CGDRSDESASCAYPTCFPLTQFTCNNGRCININWRCDNDNDCGDNSDEAGCSHSCSSTQF
KCNSGRCIPEHWTCDGDNDCGDYSDETHANCTNQATRPPGGCHTDEFQCRLDGLCIPLRW
RCDGDTDCMDSSDEKSCEGVTHVCDPSVKFGCKDSARCISKAWVCDGDNDCEDNSDEENC
ESLACRPPSHPCANNTSVCLPPDKLCDGNDDCGDGSDEGELCDQCSLNNGGCSHNCSVAP
GEGIVCSCPLGMELGPDNHTCQIQSYCAKHLKCSQKCDQNKFSVKCSCYEGWVLEPDGES
CRSLDPFKPFIIFSNRHEIRRIDLHKGDYSVLVPGLRNTIALDFHLSQSALYWTDVVEDK
IYRGKLLDNGALTSFEVVIQYGLATPEGLAVDWIAGNIYWVESNLDQIEVAKLDGTLRTT
LLAGDIEHPRAIALDPRDGILFWTDWDASLPRIEAASMSGAGRRTVHRETGSGGWPNGLT
VDYLEKRILWIDARSDAIYSARYDGSGHMEVLRGHEFLSHPFAVTLYGGEVYWTDWRTNT
LAKANKWTGHNVTVVQRTNTQPFDLQVYHPSRQPMAPNPCEANGGQGPCSHLCLINYNRT
VSCACPHLMKLHKDNTTCYEFKKFLLYARQMEIRGVDLDAPYYNYIISFTVPDIDNVTVL
DYDAREQRVYWSDVRTQAIKRAFINGTGVETVVSADLPNAHGLAVDWVSRNLFWTSYDTN
KKQINVARLDGSFKNAVVQGLEQPHGLVVHPLRGKLYWTDGDNISMANMDGSNRTLLFSG
QKGPVGLAIDFPESKLYWISSGNHTINRCNLDGSGLEVIDAMRSQLGKATALAIMGDKLW
WADQVSEKMGTCSKADGSGSVVLRNSTTLVMHMKVYDESIQLDHKGTNPCSVNNGDCSQL
CLPTSETTRSCMCTAGYSLRSGQQACEGVGSFLLYSVHEGIRGIPLDPNDKSDALVPVSG
TSLAVGIDFHAENDTIYWVDMGLSTISRAKRDQTWREDVVTNGIGRVEGIAVDWIAGNIY
WTDQGFDVIEVARLNGSFRYVVISQGLDKPRAITVHPEKGYLFWTEWGQYPRIERSRLDG
TERVVLVNVSISWPNGISVDYQDGKLYWCDARTDKIERIDLETGENREVVLSSNNMDMFS
VSVFEDFIYWSDRTHANGSIKRGSKDNATDSVPLRTGIGVQLKDIKVFNRDRQKGTNVCA
VANGGCQQLCLYRGRGQRACACAHGMLAEDGASCREYAGYLLYSERTILKSIHLSDERNL
NAPVQPFEDPEHMKNVIALAFDYRAGTSPGTPNRIFFSDIHFGNIQQINDDGSRRITIVE
NVGSVEGLAYHRGWDTLYWTSYTTSTITRHTVDQTRPGAFERETVITMSGDDHPRAFVLD
ECQNLMFWTNWNEQHPSIMRAALSGANVLTLIEKDIRTPNGLAIDHRAEKLYFSDATLDK
IERCEYDGSHRYVILKSEPVHPFGLAVYGEHIFWTDWVRRAVQRANKHVGSNMKLLRVDI
PQQPMGIIAVANDTNSCELSPCRINNGGCQDLCLLTHQGHVNCSCRGGRILQDDLTCRAV
NSSCRAQDEFECANGECINFSLTCDGVPHCKDKSDEKPSYCNSRRCKKTFRQCSNGRCVS
NMLWCNGADDCGDGSDEIPCNKTACGVGEFRCRDGTCIGNSSRCNQFVDCEDASDEMNCS
ATDCSSYFRLGVKGVLFQPCERTSLCYAPSWVCDGANDCGDYSDERDCPGVKRPRCPLNY
FACPSGRCIPMSWTCDKEDDCEHGEDETHCNKFCSEAQFECQNHRCISKQWLCDGSDDCG
DGSDEAAHCEGKTCGPSSFSCPGTHVCVPERWLCDGDKDCADGADESIAAGCLYNSTCDD
REFMCQNRQCIPKHFVCDHDRDCADGSDESPECEYPTCGPSEFRCANGRCLSSRQWECDG
ENDCHDQSDEAPKNPHCTSPEHKCNASSQFLCSSGRCVAEALLCNGQDDCGDSSDERGCH
INECLSRKLSGCSQDCEDLKIGFKCRCRPGFRLKDDGRTCADVDECSTTFPCSQRCINTH
GSYKCLCVEGYAPRGGDPHSCKAVTDEEPFLIFANRYYLRKLNLDGSNYTLLKQGLNNAV
ALDFDYREQMIYWTDVTTQGSMIRRMHLNGSNVQVLHRTGLSNPDGLAVDWVGGNLYWCD
KGRDTIEVSKLNGAYRTVLVSSGLREPRALVVDVQNGYLYWTDWGDHSLIGRIGMDGSSR
SVIVDTKITWPNGLTLDYVTERIYWADAREDYIEFASLDGSNRHVVLSQDIPHIFALTLF
EDYVYWTDWETKSINRAHKTTGTNKTLLISTLHRPMDLHVFHALRQPDVPNHPCKVNNGG
CSNLCLLSPGGGHKCACPTNFYLGSDGRTCVSNCTASQFVCKNDKCIPFWWKCDTEDDCG
DHSDEPPDCPEFKCRPGQFQCSTGICTNPAFICDGDNDCQDNSDEANCDIHVCLPSQFKC
TNTNRCIPGIFRCNGQDNCGDGEDERDCPEVTCAPNQFQCSITKRCIPRVWVCDRDNDCV
DGSDEPANCTQMTCGVDEFRCKDSGRCIPARWKCDGEDDCGDGSDEPKEECDERTCEPYQ
FRCKNNRCVPGRWQCDYDNDCGDNSDEESCTPRPCSESEFSCANGRCIAGRWKCDGDHDC
ADGSDEKDCTPRCDMDQFQCKSGHCIPLRWRCDADADCMDGSDEEACGTGVRTCPLDEFQ
CNNTLCKPLAWKCDGEDDCGDNSDENPEECARFVCPPNRPFRCKNDRVCLWIGRQCDGTD
NCGDGTDEEDCEPPTAHTTHCKDKKEFLCRNQRCLSSSLRCNMFDDCGDGSDEEDCSIDP
KLTSCATNASICGDEARCVRTEKAAYCACRSGFHTVPGQPGCQDINECLRFGTCSQLCNN
TKGGHLCSCARNFMKTHNTCKAEGSEYQVLYIADDNEIRSLFPGHPHSAYEQAFQGDESV
RIDAMDVHVKAGRVYWTNWHTGTISYRSLPPAAPPTTSNRHRRQIDRGVTHLNISGLKMP
RGIAIDWVAGNVYWTDSGRDVIEVAQMKGENRKTLISGMIDEPHAIVVDPLRGTMYWSDW
GNHPKIETAAMDGTLRETLVQDNIQWPTGLAVDYHNERLYWADAKLSVIGSIRLNGTDPI
VAADSKRGLSHPFSIDVFEDYIYGVTYINNRVFKIHKFGHSPLVNLTGGLSHASDVVLYH
QHKQPEVTNPCDRKKCEWLCLLSPSGPVCTCPNGKRLDNGTCVPVPSPTPPPDAPRPGTC
NLQCFNGGSCFLNARRQPKCRCQPRYTGDKCELDQCWEHCRNGGTCAASPSGMPTCRCPT
GFTGPKCTQQVCAGYCANNSTCTVNQGNQPQCRCLPGFLGDRCQYRQCSGYCENFGTCQM
AADGSRQCRCTAYFEGSRCEVNKCSRCLEGACVVNKQSGDVTCNCTDGRVAPSCLTCVGH
CSNGGSCTMNSKMMPECQCPPHMTGPRCEEHVFSQQQPGHIASILIPLLLLLLLVLVAGV
VFWYKRRVQGAKGFQHQRMTNGAMNVEIGNPTYKMYEGGEPDDVGGLLDADFALDPDKPT
NFTNPVYATLYMGGHGSRHSLASTDEKRELLGRGPEDEIGDPLA

• EGF (PF00008 )
• Ldl_recept_a (PF00057 )
• Ldl_recept_b (PF00058 )
• EGF_CA (PF07645 )

• 1-19

• 4420-4444

• Cell membrane

ATGCTGACCCCGCCGTTGCTCCTGCTGCTGCCCCTGCTCTCAGCTCTGGTCGCGGCGGCT
ATCGACGCCCCTAAGACTTGCAGCCCCAAGCAGTTTGCCTGCAGAGATCAAATAACCTGT
ATCTCAAAGGGCTGGCGGTGCGACGGTGAGAGGGACTGCCCAGACGGATCTGACGAGGCC
CCTGAGATTTGTCCACAGAGTAAGGCCCAGCGATGCCAGCCAAACGAGCATAACTGCCTG
GGTACTGAGCTGTGTGTTCCCATGTCCCGCCTCTGCAATGGGGTCCAGGACTGCATGGAC
GGCTCAGATGAGGGGCCCCACTGCCGAGAGCTCCAAGGCAACTGCTCTCGCCTGGGCTGC
CAGCACCATTGTGTCCCCACACTCGATGGGCCCACCTGCTACTGCAACAGCAGCTTTCAG
CTTCAGGCAGATGGCAAGACCTGCAAAGATTTTGATGAGTGCTCAGTGTACGGCACCTGC
AGCCAGCTATGCACCAACACAGACGGCTCCTTCATATGTGGCTGTGTTGAAGGATACCTC
CTGCAGCCGGATAACCGCTCCTGCAAGGCCAAGAACGAGCCAGTAGACCGGCCCCCTGTG
CTGTTGATAGCCAACTCCCAGAACATCTTGGCCACGTACCTGAGTGGGGCCCAGGTGTCT
ACCATCACACCTACGAGCACGCGGCAGACCACAGCCATGGACTTCAGCTATGCCAACGAG
ACCGTATGCTGGGTGCATGTTGGGGACAGTGCTGCTCAGACGCAGCTCAAGTGTGCCCGC
ATGCCTGGCCTAAAGGGCTTCGTGGATGAGCACACCATCAACATCTCCCTCAGTCTGCAC
CACGTGGAACAGATGGCCATCGACTGGCTGACAGGCAACTTCTACTTTGTGGATGACATC
GATGATAGGATCTTTGTCTGCAACAGAAATGGGGACACATGTGTCACATTGCTAGACCTG
GAACTCTACAACCCCAAGGGCATTGCCCTGGACCCTGCCATGGGGAAGGTGTTTTTCACT
GACTATGGGCAGATCCCAAAGGTGGAACGCTGTGACATGGATGGGCAGAACCGCACCAAG
CTCGTCGACAGCAAGATTGTGTTTCCTCATGGCATCACGCTGGACCTGGTCAGCCGCCTT
GTCTACTGGGCAGATGCCTATCTGGACTATATTGAAGTGGTGGACTATGAGGGCAAGGGC
CGCCAGACCATCATCCAGGGCATCCTGATTGAGCACCTGTACGGCCTGACTGTGTTTGAG
AATTATCTCTATGCCACCAACTCGGACAATGCCAATGCCCAGCAGAAGACGAGTGTGATC
CGTGTGAACCGCTTTAACAGCACCGAGTACCAGGTTGTCACCCGGGTGGACAAGGGTGGT
GCCCTCCACATCTACCACCAGAGGCGTCAGCCCCGAGTGAGGAGCCATGCCTGTGAAAAC
GACCAGTATGGGAAGCCGGGTGGCTGCTCTGACATCTGCCTGCTGGCCAACAGCCACAAG
GCGCGGACCTGCCGCTGCCGTTCCGGCTTCAGCCTGGGCAGTGACGGGAAGTCATGCAAG
AAGCCGGAGCATGAGCTGTTCCTCGTGTATGGCAAGGGCCGGCCAGGCATCATCCGGGGC
ATGGATATGGGGGCCAAGGTCCCGGATGAGCACATGATCCCCATTGAAAACCTCATGAAC
CCCCGAGCCCTGGACTTCCACGCTGAGACCGGCTTCATCTACTTTGCCGACACCACCAGC
TACCTCATTGGCCGCCAGAAGATTGATGGCACTGAGCGGGAGACCATCCTGAAGGACGGC
ATCCACAATGTGGAGGGTGTGGCCGTGGACTGGATGGGAGACAATCTGTACTGGACGGAC
GATGGGCCCAAAAAGACAATCAGCGTGGCCAGGCTGGAGAAAGCTGCTCAGACCCGCAAG
ACTTTAATCGAGGGCAAAATGACACACCCCAGGGCTATTGTGGTGGATCCACTCAATGGG
TGGATGTACTGGACAGACTGGGAGGAGGACCCCAAGGACAGTCGGCGTGGGCGGCTGGAG
AGGGCGTGGATGGATGGCTCACACCGAGACATCTTTGTCACCTCCAAGACAGTGCTTTGG
CCCAATGGGCTAAGCCTGGACATCCCGGCTGGGCGCCTCTACTGGGTGGATGCCTTCTAC
GACCGCATCGAGACGATACTGCTCAATGGCACAGACCGGAAGATTGTGTATGAAGGTCCT
GAGCTGAACCACGCCTTTGGCCTGTGTCACCATGGCAACTACCTCTTCTGGACTGAGTAT
CGGAGTGGCAGTGTCTACCGCTTGGAACGGGGTGTAGGAGGCGCACCCCCCACTGTGACC
CTTCTGCGCAGTGAGCGGCCCCCCATCTTTGAGATCCGAATGTATGATGCCCAGCAGCAG
CAAGTTGGCACCAACAAATGCCGGGTGAACAATGGCGGCTGCAGCAGCCTGTGCTTGGCC
ACCCCTGGGAGCCGCCAGTGCGCCTGTGCTGAGGACCAGGTGTTGGACGCAGACGGCGTC
ACTTGCTTGGCGAACCCATCCTACGTGCCTCCACCCCAGTGCCAGCCAGGCGAGTTTGCC
TGTGCCAACAGCCGCTGCATCCAGGAGCGCTGGAAGTGTGACGGAGACAACGATTGCCTG
GACAACAGTGATGAGGCCCCAGCCCTCTGCCATCAGCACACCTGCCCCTCGGACCGATTC
AAGTGCGAGAACAACCGGTGCATCCCCAACCGCTGGCTCTGCGACGGGGACAATGACTGT
GGGAACAGTGAAGATGAGTCCAATGCCACTTGTTCAGCCCGCACCTGCCCCCCCAACCAG
TTCTCCTGTGCCAGTGGCCGCTGCATCCCCATCTCCTGGACGTGTGATCTGGATGACGAC
TGTGGGGACCGCTCTGATGAGTCTGCTTCGTGTGCCTATCCCACCTGCTTCCCCCTGACT
CAGTTTACCTGCAACAATGGCAGATGTATCAACATCAACTGGAGATGCGACAATGACAAT
GACTGTGGGGACAACAGTGACGAAGCCGGCTGCAGCCACTCCTGTTCTAGCACCCAGTTC
AAGTGCAACAGCGGGCGTTGCATCCCCGAGCACTGGACCTGCGATGGGGACAATGACTGC
GGAGACTACAGTGATGAGACACACGCCAACTGCACCAACCAGGCCACGAGGCCCCCTGGT
GGCTGCCACACTGATGAGTTCCAGTGCCGGCTGGATGGACTATGCATCCCCCTGCGGTGG
CGCTGCGATGGGGACACTGACTGCATGGACTCCAGCGATGAGAAGAGCTGTGAGGGAGTG
ACCCACGTCTGCGATCCCAGTGTCAAGTTTGGCTGCAAGGACTCAGCTCGGTGCATCAGC
AAAGCGTGGGTGTGTGATGGCGACAATGACTGTGAGGATAACTCGGACGAGGAGAACTGC
GAGTCCCTGGCCTGCAGGCCACCCTCGCACCCTTGTGCCAACAACACCTCAGTCTGCCTG
CCCCCTGACAAGCTGTGTGATGGCAACGACGACTGTGGCGACGGCTCAGATGAGGGCGAG
CTCTGCGACCAGTGCTCTCTGAATAACGGTGGCTGCAGCCACAACTGCTCAGTGGCACCT
GGCGAAGGCATTGTGTGTTCCTGCCCTCTGGGCATGGAGCTGGGGCCCGACAACCACACC
TGCCAGATCCAGAGCTACTGTGCCAAGCATCTCAAATGCAGCCAAAAGTGCGACCAGAAC
AAGTTCAGCGTGAAGTGCTCCTGCTACGAGGGCTGGGTCCTGGAACCTGACGGCGAGAGC
TGCCGCAGCCTGGACCCCTTCAAGCCGTTCATCATTTTCTCCAACCGCCATGAAATCCGG
CGCATCGATCTTCACAAAGGAGACTACAGCGTCCTGGTGCCCGGCCTGCGCAACACCATC
GCCCTGGACTTCCACCTCAGCCAGAGCGCCCTCTACTGGACCGACGTGGTGGAGGACAAG
ATCTACCGCGGGAAGCTGCTGGACAACGGAGCCCTGACTAGTTTCGAGGTGGTGATTCAG
TATGGCCTGGCCACACCCGAGGGCCTGGCTGTAGACTGGATTGCAGGCAACATCTACTGG
GTGGAGAGTAACCTGGATCAGATCGAGGTGGCCAAGCTGGATGGGACCCTCCGGACCACC
CTGCTGGCCGGTGACATTGAGCACCCAAGGGCAATCGCACTGGATCCCCGGGATGGGATC
CTGTTTTGGACAGACTGGGATGCCAGCCTGCCCCGCATTGAGGCAGCCTCCATGAGTGGG
GCTGGGCGCCGCACCGTGCACCGGGAGACCGGCTCTGGGGGCTGGCCCAACGGGCTCACC
GTGGACTACCTGGAGAAGCGCATCCTTTGGATTGACGCCAGGTCAGATGCCATTTACTCA
GCCCGTTACGACGGCTCTGGCCACATGGAGGTGCTTCGGGGACACGAGTTCCTGTCGCAC
CCGTTTGCAGTGACGCTGTACGGGGGGGAGGTCTACTGGACTGACTGGCGAACAAACACA
CTGGCTAAGGCCAACAAGTGGACCGGCCACAATGTCACCGTGGTACAGAGGACCAACACC
CAGCCCTTTGACCTGCAGGTGTACCACCCCTCCCGCCAGCCCATGGCTCCCAATCCCTGT
GAGGCCAATGGGGGCCAGGGCCCCTGCTCCCACCTGTGTCTCATCAACTACAACCGGACC
GTGTCCTGCGCCTGCCCCCACCTCATGAAGCTCCACAAGGACAACACCACCTGCTATGAG
TTTAAGAAGTTCCTGCTGTACGCACGTCAGATGGAGATCCGAGGTGTGGACCTGGATGCT
CCCTACTACAACTACATCATCTCCTTCACGGTGCCCGACATCGACAACGTCACAGTGCTA
GACTACGATGCCCGCGAGCAGCGTGTGTACTGGTCTGACGTGCGGACACAGGCCATCAAG
CGGGCCTTCATCAACGGCACAGGCGTGGAGACAGTCGTCTCTGCAGACTTGCCAAATGCC
CACGGGCTGGCTGTGGACTGGGTCTCCCGAAACCTGTTCTGGACAAGCTATGACACCAAT
AAGAAGCAGATCAATGTGGCCCGGCTGGATGGCTCCTTCAAGAACGCAGTGGTGCAGGGC
CTGGAGCAGCCCCATGGCCTTGTCGTCCACCCTCTGCGTGGGAAGCTCTACTGGACCGAT
GGTGACAACATCAGCATGGCCAACATGGATGGCAGCAATCGCACCCTGCTCTTCAGTGGC
CAGAAGGGCCCCGTGGGCCTGGCTATTGACTTCCCTGAAAGCAAACTCTACTGGATCAGC
TCCGGGAACCATACCATCAACCGCTGCAACCTGGATGGGAGTGGGCTGGAGGTCATCGAT
GCCATGCGGAGCCAGCTGGGCAAGGCCACCGCCCTGGCCATCATGGGGGACAAGCTGTGG
TGGGCTGATCAGGTGTCGGAAAAGATGGGCACATGCAGCAAGGCTGACGGCTCGGGCTCC
GTGGTCCTTCGGAACAGCACCACCCTGGTGATGCACATGAAGGTCTATGACGAGAGCATC
CAGCTGGACCATAAGGGCACCAACCCCTGCAGTGTCAACAACGGTGACTGCTCCCAGCTC
TGCCTGCCCACGTCAGAGACGACCCGCTCCTGCATGTGCACAGCCGGCTATAGCCTCCGG
AGTGGCCAGCAGGCCTGCGAGGGCGTAGGTTCCTTTCTCCTGTACTCTGTGCATGAGGGA
ATCAGGGGAATTCCCCTGGATCCCAATGACAAGTCAGATGCCCTGGTCCCAGTGTCCGGG
ACCTCGCTGGCTGTCGGCATCGACTTCCACGCTGAAAATGACACCATCTACTGGGTGGAC
ATGGGCCTGAGCACGATCAGCCGGGCCAAGCGGGACCAGACGTGGCGTGAAGACGTGGTG
ACCAATGGCATTGGCCGTGTGGAGGGCATTGCAGTGGACTGGATCGCAGGCAACATCTAC
TGGACAGACCAGGGCTTTGATGTCATCGAGGTCGCCCGGCTCAATGGCTCCTTCCGCTAC
GTGGTGATCTCCCAGGGTCTAGACAAGCCCCGGGCCATCACCGTCCACCCGGAGAAAGGG
TACTTGTTCTGGACTGAGTGGGGTCAGTATCCGCGTATTGAGCGGTCTCGGCTAGATGGC
ACGGAGCGTGTGGTGCTGGTCAACGTCAGCATCAGCTGGCCCAACGGCATCTCAGTGGAC
TACCAGGATGGGAAGCTGTACTGGTGCGATGCACGGACAGACAAGATTGAACGGATCGAC
CTGGAGACAGGTGAGAACCGCGAGGTGGTTCTGTCCAGCAACAACATGGACATGTTTTCA
GTGTCTGTGTTTGAGGATTTCATCTACTGGAGTGACAGGACTCATGCCAACGGCTCTATC
AAGCGCGGGAGCAAAGACAATGCCACAGACTCCGTGCCCCTGCGAACCGGCATCGGCGTC
CAGCTTAAAGACATCAAAGTCTTCAACCGGGACCGGCAGAAAGGCACCAACGTGTGCGCG
GTGGCCAATGGCGGGTGCCAGCAGCTGTGCCTGTACCGGGGCCGTGGGCAGCGGGCCTGC
GCCTGTGCCCACGGGATGCTGGCTGAAGACGGAGCATCGTGCCGCGAGTATGCCGGCTAC
CTGCTCTACTCAGAGCGCACCATTCTCAAGAGTATCCACCTGTCGGATGAGCGCAACCTC
AATGCGCCCGTGCAGCCCTTCGAGGACCCTGAGCACATGAAGAACGTCATCGCCCTGGCC
TTTGACTACCGGGCAGGCACCTCTCCGGGCACCCCCAATCGCATCTTCTTCAGCGACATC
CACTTTGGGAACATCCAACAGATCAACGACGATGGCTCCAGGAGGATCACCATTGTGGAA
AACGTGGGCTCCGTGGAAGGCCTGGCCTATCACCGTGGCTGGGACACTCTCTATTGGACA
AGCTACACGACATCCACCATCACGCGCCACACAGTGGACCAGACCCGCCCAGGGGCCTTC
GAGCGTGAGACCGTCATCACTATGTCTGGAGATGACCACCCACGGGCCTTCGTTTTGGAC
GAGTGCCAGAACCTCATGTTCTGGACCAACTGGAATGAGCAGCATCCCAGCATCATGCGG
GCGGCGCTCTCGGGAGCCAATGTCCTGACCCTTATCGAGAAGGACATCCGTACCCCCAAT
GGCCTGGCCATCGACCACCGTGCCGAGAAGCTCTACTTCTCTGACGCCACCCTGGACAAG
ATCGAGCGGTGCGAGTATGACGGCTCCCACCGCTATGTGATCCTAAAGTCAGAGCCTGTC
CACCCCTTCGGGCTGGCCGTGTATGGGGAGCACATTTTCTGGACTGACTGGGTGCGGCGG
GCAGTGCAGCGGGCCAACAAGCACGTGGGCAGCAACATGAAGCTGCTGCGCGTGGACATC
CCCCAGCAGCCCATGGGCATCATCGCCGTGGCCAACGACACCAACAGCTGTGAACTCTCT
CCATGCCGAATCAACAACGGTGGCTGCCAGGACCTGTGTCTGCTCACTCACCAGGGCCAT
GTCAACTGCTCATGCCGAGGGGGCCGAATCCTCCAGGATGACCTCACCTGCCGAGCGGTG
AATTCCTCTTGCCGAGCACAAGATGAGTTTGAGTGTGCCAATGGCGAGTGCATCAACTTC
AGCCTGACCTGCGACGGCGTCCCCCACTGCAAGGACAAGTCCGATGAGAAGCCATCCTAC
TGCAACTCCCGCCGCTGCAAGAAGACTTTCCGGCAGTGCAGCAATGGGCGCTGTGTGTCC
AACATGCTGTGGTGCAACGGGGCCGACGACTGTGGGGATGGCTCTGACGAGATCCCTTGC
AACAAGACAGCCTGTGGTGTGGGCGAGTTCCGCTGCCGGGACGGGACCTGCATCGGGAAC
TCCAGCCGCTGCAACCAGTTTGTGGATTGTGAGGACGCCTCAGATGAGATGAACTGCAGT
GCCACCGACTGCAGCAGCTACTTCCGCCTGGGCGTGAAGGGCGTGCTCTTCCAGCCCTGC
GAGCGGACCTCACTCTGCTACGCACCCAGCTGGGTGTGTGATGGCGCCAATGACTGTGGG
GACTACAGTGATGAGCGCGACTGCCCAGGTGTGAAACGCCCCAGATGCCCTCTGAATTAC
TTCGCCTGCCCTAGTGGGCGCTGCATCCCCATGAGCTGGACGTGTGACAAAGAGGATGAC
TGTGAACATGGCGAGGACGAGACCCACTGCAACAAGTTCTGCTCAGAGGCCCAGTTTGAG
TGCCAGAACCATCGCTGCATCTCCAAGCAGTGGCTGTGTGACGGCAGCGATGACTGTGGG
GATGGCTCAGACGAGGCTGCTCACTGTGAAGGCAAGACGTGCGGCCCCTCCTCCTTCTCC
TGCCCTGGCACCCACGTGTGCGTCCCCGAGCGCTGGCTCTGTGACGGTGACAAAGACTGT
GCTGATGGTGCAGACGAGAGCATCGCAGCTGGTTGCTTGTACAACAGCACTTGTGACGAC
CGTGAGTTCATGTGCCAGAACCGCCAGTGCATCCCCAAGCACTTCGTGTGTGACCACGAC
CGTGACTGTGCAGATGGCTCTGATGAGTCCCCCGAGTGTGAGTACCCGACCTGCGGCCCC
AGTGAGTTCCGCTGTGCCAATGGGCGCTGTCTGAGCTCCCGCCAGTGGGAGTGTGATGGC
GAGAATGACTGCCACGACCAGAGTGACGAGGCTCCCAAGAACCCACACTGCACCAGCCCA
GAGCACAAGTGCAATGCCTCGTCACAGTTCCTGTGCAGCAGTGGGCGCTGTGTGGCTGAG
GCACTGCTCTGCAACGGCCAGGATGACTGTGGCGACAGCTCGGACGAGCGTGGCTGCCAC
ATCAATGAGTGTCTCAGCCGCAAGCTCAGTGGCTGCAGCCAGGACTGTGAGGACCTCAAG
ATCGGCTTCAAGTGCCGCTGTCGCCCTGGCTTCCGGCTGAAGGATGACGGCCGGACGTGT
GCTGATGTGGACGAGTGCAGCACCACCTTCCCCTGCAGCCAGCGCTGCATCAACACCCAT
GGCAGCTATAAGTGTCTGTGTGTGGAGGGCTATGCACCCCGCGGCGGCGACCCCCACAGC
TGCAAGGCTGTGACTGACGAGGAACCGTTTCTGATCTTCGCCAACCGGTACTACCTGCGC
AAGCTCAACCTGGACGGGTCCAACTACACGTTACTTAAGCAGGGCCTGAACAACGCCGTT
GCCTTGGATTTTGACTACCGAGAGCAGATGATCTACTGGACAGATGTGACCACCCAGGGC
AGCATGATCCGAAGGATGCACCTTAACGGGAGCAATGTGCAGGTCCTACACCGTACAGGC
CTCAGCAACCCCGATGGGCTGGCTGTGGACTGGGTGGGTGGCAACCTGTACTGGTGCGAC
AAAGGCCGGGACACCATCGAGGTGTCCAAGCTCAATGGGGCCTATCGGACGGTGCTGGTC
AGCTCTGGCCTCCGTGAGCCCAGGGCTCTGGTGGTGGATGTGCAGAATGGGTACCTGTAC
TGGACAGACTGGGGTGACCATTCACTGATCGGCCGCATCGGCATGGATGGGTCCAGCCGC
AGCGTCATCGTGGACACCAAGATCACATGGCCCAATGGCCTGACGCTGGACTATGTCACT
GAGCGCATCTACTGGGCCGACGCCCGCGAGGACTACATTGAATTTGCCAGCCTGGATGGC
TCCAATCGCCACGTTGTGCTGAGCCAGGACATCCCGCACATCTTTGCACTGACCCTGTTT
GAGGACTACGTCTACTGGACCGACTGGGAAACAAAGTCCATTAACCGAGCCCACAAGACC
ACGGGCACCAACAAAACGCTCCTCATCAGCACGCTGCACCGGCCCATGGACCTGCATGTC
TTCCATGCCCTGCGCCAGCCAGACGTGCCCAATCACCCCTGCAAGGTCAACAATGGTGGC
TGCAGCAACCTGTGCCTGCTGTCCCCCGGGGGAGGGCACAAATGTGCCTGCCCCACCAAC
TTCTACCTGGGCAGCGATGGGCGCACCTGTGTGTCCAACTGCACGGCTAGCCAGTTTGTA
TGCAAGAACGACAAGTGCATCCCCTTCTGGTGGAAGTGTGACACCGAGGACGACTGCGGG
GACCACTCAGACGAGCCCCCGGACTGCCCTGAGTTCAAGTGCCGGCCCGGACAGTTCCAG
TGCTCCACAGGTATCTGCACAAACCCTGCCTTCATCTGCGATGGCGACAATGACTGCCAG
GACAACAGTGACGAGGCCAACTGTGACATCCACGTCTGCTTGCCCAGTCAGTTCAAATGC
ACCAACACCAACCGCTGTATTCCCGGCATCTTCCGCTGCAATGGGCAGGACAACTGCGGA
GATGGGGAGGATGAGAGGGACTGCCCCGAGGTGACCTGCGCCCCCAACCAGTTCCAGTGC
TCCATTACCAAACGGTGCATCCCCCGGGTCTGGGTCTGCGACCGGGACAATGACTGTGTG
GATGGCAGTGATGAGCCCGCCAACTGCACCCAGATGACCTGTGGTGTGGACGAGTTCCGC
TGCAAGGATTCGGGCCGCTGCATCCCAGCGCGTTGGAAGTGTGACGGAGAGGATGACTGT
GGGGATGGCTCGGATGAGCCCAAGGAAGAGTGTGATGAACGCACCTGTGAGCCATACCAG
TTCCGCTGCAAGAACAACCGCTGCGTGCCCGGCCGCTGGCAGTGCGACTACGACAACGAT
TGCGGTGACAACTCCGATGAAGAGAGCTGCACCCCTCGGCCCTGCTCCGAGAGTGAGTTC
TCCTGTGCCAACGGCCGCTGCATCGCGGGGCGCTGGAAATGCGATGGAGACCACGACTGC
GCGGACGGCTCGGACGAGAAAGACTGCACCCCCCGCTGTGACATGGACCAGTTCCAGTGC
AAGAGCGGCCACTGCATCCCCCTGCGCTGGCGCTGTGACGCAGACGCCGACTGCATGGAC
GGCAGCGACGAGGAGGCCTGCGGCACTGGCGTGCGGACCTGCCCCCTGGACGAGTTCCAG
TGCAACAACACCTTGTGCAAGCCGCTGGCCTGGAAGTGCGATGGCGAGGATGACTGTGGG
GACAACTCAGATGAGAACCCCGAGGAGTGTGCCCGGTTCGTGTGCCCTCCCAACCGGCCC
TTCCGTTGCAAGAATGACCGCGTCTGTCTGTGGATCGGGCGCCAATGCGATGGCACGGAC
AACTGTGGGGATGGGACTGATGAAGAGGACTGTGAGCCCCCCACAGCCCACACCACCCAC
TGCAAAGACAAGAAGGAGTTTCTGTGCCGGAACCAGCGCTGCCTCTCCTCCTCCCTGCGC
TGCAACATGTTCGATGACTGCGGGGACGGCTCTGACGAGGAGGACTGCAGCATCGACCCC
AAGCTGACCAGCTGCGCCACCAATGCCAGCATCTGTGGGGACGAGGCACGCTGCGTGCGC
ACCGAGAAAGCGGCCTACTGTGCCTGCCGCTCGGGCTTCCACACCGTGCCCGGCCAGCCC
GGATGCCAAGACATCAACGAGTGCCTGCGCTTCGGCACCTGCTCCCAGCTCTGCAACAAC
ACCAAGGGCGGCCACCTCTGCAGCTGCGCTCGGAACTTCATGAAGACGCACAACACCTGC
AAGGCCGAAGGCTCTGAGTACCAGGTCCTGTACATCGCTGATGACAATGAGATCCGCAGC
CTGTTCCCCGGCCACCCCCATTCGGCTTACGAGCAGGCATTCCAGGGTGACGAGAGTGTC
CGCATTGATGCTATGGATGTCCATGTCAAGGCTGGCCGTGTCTATTGGACCAACTGGCAC
ACGGGCACCATCTCCTACCGCAGCCTGCCACCTGCTGCGCCTCCTACCACTTCCAACCGC
CACCGGCGACAGATTGACCGGGGTGTCACCCACCTCAACATTTCAGGGCTGAAGATGCCC
AGAGGCATCGCCATCGACTGGGTGGCCGGAAACGTGTACTGGACCGACTCGGGCCGAGAT
GTGATTGAGGTGGCGCAGATGAAGGGCGAGAACCGCAAGACGCTCATCTCGGGCATGATT
GACGAGCCCCACGCCATTGTGGTGGACCCACTGAGGGGGACCATGTACTGGTCAGACTGG
GGCAACCACCCCAAGATTGAGACGGCAGCGATGGATGGGACGCTTCGGGAGACACTGGTG
CAGGACAACATTCAGTGGCCCACAGGCCTGGCCGTGGATTATCACAATGAGCGGCTGTAC
TGGGCAGACGCCAAGCTTTCAGTCATCGGCAGCATCCGGCTCAATGGCACGGACCCCATT
GTGGCTGCTGACAGCAAACGAGGCCTAAGTCACCCCTTCAGCATCGACGTCTTTGAGGAT
TACATCTATGGTGTCACCTACATCAATAATCGTGTCTTCAAGATCCATAAGTTTGGCCAC
AGCCCCTTGGTCAACCTGACAGGGGGCCTGAGCCACGCCTCTGACGTGGTCCTTTACCAT
CAGCACAAGCAGCCCGAAGTGACCAACCCATGTGACCGCAAGAAATGCGAGTGGCTCTGC
CTGCTGAGCCCCAGTGGGCCTGTCTGCACCTGTCCCAATGGGAAGCGGCTGGACAACGGC
ACATGCGTGCCTGTGCCCTCTCCAACGCCCCCCCCAGATGCTCCCCGGCCTGGAACCTGT
AACCTGCAGTGCTTCAACGGTGGCAGCTGTTTCCTCAATGCACGGAGGCAGCCCAAGTGC
CGCTGCCAACCCCGCTACACGGGTGACAAGTGTGAACTGGACCAGTGCTGGGAGCACTGT
CGCAATGGGGGCACCTGTGCTGCCTCCCCCTCTGGCATGCCCACGTGCCGGTGCCCCACG
GGCTTCACGGGCCCCAAATGCACCCAGCAGGTGTGTGCGGGCTACTGTGCCAACAACAGC
ACCTGCACTGTCAACCAGGGCAACCAGCCCCAGTGCCGATGCCTACCCGGCTTCCTGGGC
GACCGCTGCCAGTACCGGCAGTGCTCTGGCTACTGTGAGAACTTTGGCACATGCCAGATG
GCTGCTGATGGCTCCCGACAATGCCGCTGCACTGCCTACTTTGAGGGATCGAGGTGTGAG
GTGAACAAGTGCAGCCGCTGTCTCGAAGGGGCCTGTGTGGTCAACAAGCAGAGTGGGGAT
GTCACCTGCAACTGCACGGATGGCCGGGTGGCCCCCAGCTGTCTGACCTGCGTCGGCCAC
TGCAGCAATGGCGGCTCCTGTACCATGAACAGCAAAATGATGCCTGAGTGCCAGTGCCCA
CCCCACATGACAGGGCCCCGGTGTGAGGAGCACGTCTTCAGCCAGCAGCAGCCAGGACAT
ATAGCCTCCATCCTAATCCCTCTGCTGTTGCTGCTGCTGCTGGTTCTGGTGGCCGGAGTG
GTATTCTGGTATAAGCGGCGAGTCCAAGGGGCTAAGGGCTTCCAGCACCAACGGATGACC
AACGGGGCCATGAACGTGGAGATTGGAAACCCCACCTACAAGATGTACGAAGGCGGAGAG
CCTGATGATGTGGGAGGCCTACTGGACGCTGACTTTGCCCTGGACCCTGACAAGCCCACC
AACTTCACCAACCCCGTGTATGCCACACTCTACATGGGGGGCCATGGCAGTCGCCACTCC
CTGGCCAGCACGGACGAGAAGCGAGAACTCCTGGGCCGGGGCCCTGAGGACGAGATAGGG
GACCCCTTGGCATAG

1. Kristensen T, Moestrup SK, Gliemann J, Bendtsen L, Sand O, Sottrup-Jensen L: Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett. 1990 Dec 10;276(1-2):151-5. [PubMed ]
2. Herz J, Kowal RC, Goldstein JL, Brown MS: Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment. EMBO J. 1990 Jun;9(6):1769-76. [PubMed ]
3. Kutt H, Herz J, Stanley KK: Structure of the low-density lipoprotein receptor-related protein (LRP) promoter. Biochim Biophys Acta. 1989 Dec 22;1009(3):229-36. [PubMed ]
4. Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK: Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J. 1988 Dec 20;7(13):4119-27. [PubMed ]
5. Van Leuven F, Stas L, Hilliker C, Lorent K, Umans L, Serneels L, Overbergh L, Torrekens S, Moechars D, De Strooper B, et al.: Structure of the gene (LRP1) coding for the human alpha 2-macroglobulin receptor lipoprotein receptor-related protein. Genomics. 1994 Nov 1;24(1):78-89. [PubMed ]
6. Van Leuven F, Stas L, Thiry E, Nelissen B, Miyake Y: Strategy to sequence the 89 exons of the human LRP1 gene coding for the lipoprotein receptor related protein: identification of one expressed mutation among 48 polymorphisms. Genomics. 1998 Sep 1;52(2):138-44. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. EC 1.14.11.18
2. PhyH
3. Phytanic acid oxidase
4. Phytanoyl-CoA alpha-hydroxylase
5. Phytanoyl-CoA dioxygenase, peroxisomal precursor

MEQLRAAARLQIVLGHLGRPSAGAVVAHPTSGTISSASFHPQQFQYTLDNNVLTLEQRKF
YEENGFLVIKNLVPDADIQRFRNEFEKICRKEVKPLGLTVMRDVTISKSEYAPSEKMITK
VQDFQEDKELFRYCTLPEILKYVECFTGPNIMAMHTMLINKPPDSGKKTSRHPLHQDLHY
FPFRPSDLIVCAWTAMEHISRNNGCLVVLPGTHKGSLKPHDYPKWEGGVNKMFHGIQDYE
ENKARVHLVMEKGDTVFFHPLLIHGSGQNKTQGFRKAISCHFASADCHYIDVKGTSQENI
EKEVVGIAHKFFGAENSVNLKDIWMFRARLVKGERTNL

• phytanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyphytanoyl-CoA + succinate + CO2

• PhyH (PF05721 )

• None

• None

• Peroxisome

ATGGAGCAGCTTCGCGCCGCCGCCCGTCTGCAGATTGTTCTGGGCCACCTCGGCCGCCCC
TCGGCCGGGGCTGTCGTAGCTCATCCCACTTCAGGGACTATTTCCTCTGCCAGTTTCCAT
CCTCAACAATTCCAGTATACTCTGGATAATAATGTTCTAACCCTGGAACAGAGAAAATTT
TATGAAGAAAATGGGTTTCTAGTAATCAAAAATCTTGTACCTGATGCCGATATTCAACGC
TTTCGGAATGAGTTTGAAAAAATCTGCAGAAAGGAGGTGAAACCATTAGGATTAACAGTA
ATGAGAGATGTGACCATTTCGAAATCCGAATATGCTCCAAGTGAGAAGATGATCACGAAG
GTCCAGGATTTCCAGGAAGATAAGGAGCTCTTCAGATACTGCACTCTCCCCGAGATTCTG
AAATATGTGGAGTGCTTCACTGGACCTAATATTATGGCCATGCACACAATGTTGATAAAC
AAACCTCCAGATTCTGGCAAGAAGACGTCCCGTCACCCCCTGCACCAGGACCTGCACTAT
TTCCCCTTCAGGCCCAGCGATCTCATCGTTTGCGCCTGGACGGCGATGGAGCACATCAGC
CGGAACAACGGCTGTCTGGTTGTGCTCCCAGGCACGCACAAGGGCTCCCTGAAGCCCCAC
GATTACCCCAAGTGGGAGGGGGGAGTTAACAAAATGTTCCACGGGATCCAGGACTACGAG
GAAAACAAGGCCCGGGTGCACCTGGTGATGGAGAAGGGCGACACTGTTTTCTTCCATCCT
TTGCTCATCCACGGATCTGGTCAGAATAAAACCCAGGGATTCCGGAAGGCAATTTCCTGC
CATTTCGCCAGTGCCGATTGCCACTACATTGACGTGAAGGGCACCAGTCAAGAAAACATC
GAGAAGGAAGTTGTAGGAATAGCACATAAATTCTTTGGAGCTGAAAATAGCGTGAACTTG
AAGGATATTTGGATGTTTCGAGCTCGACTTGTGAAAGGAGAAAGAACCAATCTTTGA

1. Chambraud B, Radanyi C, Camonis JH, Rajkowski K, Schumacher M, Baulieu EE: Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-COA alpha-hydroxylase is a new FKBP-associated protein. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2104-9. [PubMed ]
2. Lee ZH, Kim H, Ahn KY, Seo KH, Kim JK, Bae CS, Kim KK: Identification of a brain specific protein that associates with a refsum disease gene product, phytanoyl-CoA alpha-hydroxylase. Brain Res Mol Brain Res. 2000 Feb 22;75(2):237-47. [PubMed ]
3. Jansen GA, Ferdinandusse S, Hogenhout EM, Verhoeven NM, Jakobs C, Wanders RJ: Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease. Adv Exp Med Biol. 1999;466:371-6. [PubMed ]
4. Jansen GA, Hogenhout EM, Ferdinandusse S, Waterham HR, Ofman R, Jakobs C, Skjeldal OH, Wanders RJ: Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. Hum Mol Genet. 2000 May 1;9(8):1195-200. [PubMed ]
5. Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ: Identification of PAHX, a Refsum disease gene. Nat Genet. 1997 Oct;17(2):185-9. [PubMed ]
6. Jansen GA, Ofman R, Ferdinandusse S, Ijlst L, Muijsers AO, Skjeldal OH, Stokke O, Jakobs C, Besley GT, Wraith JE, Wanders RJ: Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. 1997 Oct;17(2):190-3. [PubMed ]

1. Chen C, Wang Q, Fang X, Xu Q, Chi C, Gu J: Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII. J Biol Chem. 2001 Dec 7;276(49):46340-6. [PubMed ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
3. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. ASGP-R 2
2. ASGPR 2
3. Hepatic lectin H2

MAKDFQDIQQLSSEENDHPFHQGEGPGTRRLNPRRGNPFLKGPPPAQPLAQRLCSMVCFS
LLALSFNILLLVVICVTGSQSEGHRGAQLQAELRSLKEAFSNFSSSTLTEVQAISTHGGS
VGDKITSLGAKLEKQQQDLKADHDALLFHLKHFPVDLRFVACQMELLHSNGSQRTCCPVN
WVEHQGSCYWFSHSGKAWAEAEKYCQLENAHLVVINSWEEQKFIVQHTNPFNTWIGLTDS
DGSWKWVDGTDYRHNYKNWAVTQPDNWHGHELGGSEDCVEVQPDGRWNDDFCLQVYRWVC
EKRRNATGEVA

• Lectin_C (PF00059 )
• Lectin_N (PF03954 )

• None

• 59-79

• Membrane

ATGGCCAAGGACTTTCAAGATATCCAGCAGCTGAGCTCGGAGGAAAATGACCATCCTTTC
CATCAAGGTGAGGGGCCAGGCACTCGCAGGCTGAATCCCAGGAGAGGAAATCCATTTTTG
AAAGGGCCACCTCCTGCCCAGCCCCTGGCACAGCGTCTCTGCTCCATGGTCTGCTTCAGT
CTGCTTGCCCTGAGCTTCAACATCCTGCTGCTGGTGGTCATCTGTGTGACTGGGTCCCAA
AGTGAGGGTCACAGAGGTGCACAGCTGCAAGCCGAGCTGCGGAGCCTGAAGGAAGCTTTC
AGCAACTTCTCCTCGAGCACCCTGACGGAGGTCCAGGCAATCAGCACCCACGGAGGCAGC
GTGGGTGACAAGATCACATCCCTAGGAGCCAAGCTGGAGAAACAGCAGCAGGACCTGAAA
GCAGATCACGATGCCCTGCTCTTCCATCTGAAGCACTTCCCCGTGGACCTGCGCTTCGTG
GCCTGCCAGATGGAGCTCCTCCACAGCAACGGCTCCCAAAGGACCTGCTGCCCCGTCAAC
TGGGTGGAGCACCAAGGCAGCTGCTACTGGTTCTCTCACTCCGGGAAGGCCTGGGCTGAG
GCGGAGAAGTACTGCCAGCTGGAGAACGCACACCTGGTGGTCATCAACTCCTGGGAGGAG
CAGAAATTCATTGTACAACACACGAACCCCTTCAATACCTGGATAGGTCTCACGGACAGT
GATGGCTCTTGGAAATGGGTGGATGGCACAGACTATAGGCACAACTACAAGAACTGGGCT
GTCACTCAGCCAGATAATTGGCACGGGCACGAGCTGGGTGGAAGTGAAGACTGTGTTGAA
GTCCAGCCGGATGGCCGCTGGAACGATGACTTCTGCCTGCAGGTGTACCGCTGGGTGTGT
GAGAAAAGGCGGAATGCCACCGGCGAGGTGGCCTGA

1. Pan H, Qin WX, Huo KK, Wan DF, Yu Y, Xu ZG, Hu QD, Gu KT, Zhou XM, Jiang HQ, Zhang PP, Huang Y, Li YY, Gu JR: Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics. 2001 Sep;77(1-2):58-64. [PubMed ]
2. Paietta E, Stockert RJ, Racevskis J: Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver. Hepatology. 1992 Mar;15(3):395-402. [PubMed ]
3. Spiess M, Lodish HF: Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6465-9. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. ER-Golgi intermediate compartment 53 kDa protein
2. ERGIC-53 protein precursor
3. Gp58
4. Intracellular mannose- specific lectin MR60
5. Lectin, mannose-binding 1

MAGSRQRGLRARVRPLFCALLLSLGRFVRGDGVGGDPAVALPHRRFEYKYSFKGPHLVQS
DGTVPFWAHAGNAIPSSDQIRVAPSLKSQRGSVWTKTKAAFENWEVEVTFRVTGRGRIGA
DGLAIWYAENQGLEGPVFGSADLWNGVGIFFDSFDNDGKKNNPAIVIIGNNGQIHYDHQN
DGASQALASCQRDFRNKPYPVRAKITYYQNTLTVMINNGFTPDKNDYEFCAKVENMIIPA
QGHFGISAATGGLADDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQEL
DKKKEEFQKGHPDLQGQPAEEIFESVGDRELRQVFEGQNRIHLEIKQLNRQLDMILDEQR
RYVSSLTEEISKRGAGMPGQHGQITQQELDTVVKTQHEILRQVNEMKNSMSETVRLVSGM
QHPGSAGGVYETTQHFIDIKEHLHIVKRDIDNLVQRNMPSNEKPKCPELPPFPSCLSTVH
FIIFVVVQTVLFIGYIMYRSQQEAAAKKFF

• Lectin_leg-like (PF03388 )

• 1-30

• 478-498

• Endoplasmic reticulum-Golgi intermediate compartment

ATGGCGGGATCCAGGCAAAGGGGTCTCCGGGCCAGAGTTCGGCCGCTGTTCTGCGCCTTG
CTGCTGTCACTCGGTCGCTTCGTCCGGGGCGACGGCGTGGGAGGAGACCCCGCGGTCGCG
TTGCCACATCGCCGTTTCGAGTACAAATACAGCTTCAAGGGGCCGCACCTGGTGCAGAGC
GACGGGACCGTGCCCTTCTGGGCCCACGCGGGGAATGCTATTCCAAGTTCAGATCAAATT
CGAGTAGCACCATCTTTAAAAAGCCAAAGAGGCTCAGTGTGGACAAAGACAAAAGCGGCC
TTTGAGAACTGGGAAGTTGAGGTGACATTTCGAGTGACTGGAAGAGGTCGAATTGGAGCT
GATGGCCTAGCAATTTGGTATGCAGAAAATCAAGGCTTGGAGGGCCCTGTGTTTGGATCA
GCTGATCTGTGGAATGGTGTTGGAATATTTTTTGATACTTTTGACAATGATGGAAAGAAA
AATAATCCTGCTATAGTAATTATAGGCAACAATGGACAAATCCATTATGACCATCAAAAT
GACGGGGCTAGTCAAGCTTTGGCAAGTTGCCAGAGGGACTTCCGCAACAAACCCTATCCT
GTCCGAGCAAAGATTACCTATTACCAGAACACACTGACAGTAATGATCAATAATGGCTTT
ACACCAGATAAAAATGATTATGAATTTTGTGCCAAAGTGGAAAATATGATTATCCCTGCA
CAAGGGCATTTTGGAATATCTGCTGCAACTGGAGGTCTTGCAGATGACCATGATGTCCTT
TCTTTTCTGACTTTCCAGTTGACTGAACCTGGAAAAGAGCCGCCCACACCAGATAAAGAA
ATTTCGGAAAAGGAAAAAGAAAAGTATCAGGAGGAATTTGAGCACTTTCAACAAGAATTG
GATAAAAAAAAAGAGGAATTCCAGAAGGGCCACCCCGACCTCCAAGGGCAGCCTGCGGAG
GAAATATTTGAGAGTGTAGGAGATCGAGAGCTAAGACAAGTCTTTGAAGGACAGAATCGT
ATTCATCTTGAAATCAAGCAGCTGAACCGGCAGTTAGATATGATTCTTGATGAACAGAGA
AGATATGTCTCTTCCTTAACAGAGGAAATCTCTAAAAGAGGAGCAGGAATGCCTGGGCAG
CATGGGCAGATTACTCAACAAGAACTGGATACTGTTGTGAAAACTCAGCATGAGATTCTG
AGACAAGTAAATGAAATGAAAAATTCCATGAGTGAAACCGTCAGACTGGTCAGTGGAATG
CAGCACCCTGGCTCTGCTGGAGGCGTCTATGAGACAACACAGCACTTCATTGACATCAAA
GAGCACCTGCACATAGTAAAGAGGGACATAGATAACTTAGTGCAGCGAAATATGCCATCA
AATGAAAAGCCGAAATGCCCAGAACTACCACCATTTCCATCATGTTTGTCTACGGTCCAC
TTCATTATATTTGTTGTGGTGCAAACTGTATTATTCATTGGTTATATCATGTATAGGTCT
CAGCAAGAAGCAGCTGCCAAAAAATTCTTTTGA

1. Nichols WC, Terry VH, Wheatley MA, Yang A, Zivelin A, Ciavarella N, Stefanile C, Matsushita T, Saito H, de Bosch NB, Ruiz-Saez A, Torres A, Thompson AR, Feinstein DI, White GC, Negrier C, Vinciguerra C, Aktan M, Kaufman RJ, Ginsburg D, Seligsohn U: ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood. 1999 Apr 1;93(7):2261-6. [PubMed ]
2. Harris RA, Yang A, Stein RC, Lucy K, Brusten L, Herath A, Parekh R, Waterfield MD, O'Hare MJ, Neville MA, Page MJ, Zvelebil MJ: Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23. [PubMed ]
3. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed ]
4. Arar C, Carpentier V, Le Caer JP, Monsigny M, Legrand A, Roche AC: ERGIC-53, a membrane protein of the endoplasmic reticulum-Golgi intermediate compartment, is identical to MR60, an intracellular mannose-specific lectin of myelomonocytic cells. J Biol Chem. 1995 Feb 24;270(8):3551-3. [PubMed ]
5. Fiedler K, Simons K: A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins. Cell. 1994 Jun 3;77(5):625-6. [PubMed ]
6. Schindler R, Itin C, Zerial M, Lottspeich F, Hauri HP: ERGIC-53, a membrane protein of the ER-Golgi intermediate compartment, carries an ER retention motif. Eur J Cell Biol. 1993 Jun;61(1):1-9. [PubMed ]

1. Cunningham MA, Pipe SW, Zhang B, Hauri HP, Ginsburg D, Kaufman RJ: LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII. J Thromb Haemost. 2003 Nov;1(11):2360-7. [PubMed ]
2. Miao HZ, Sirachainan N, Palmer L, Kucab P, Cunningham MA, Kaufman RJ, Pipe SW: Bioengineering of coagulation factor VIII for improved secretion. Blood. 2004 May 1;103(9):3412-9. Epub 2004 Jan 15. [PubMed ]
3. [PubMed ]
4. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
5. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Multiple coagulation factor deficiency protein 2 precursor
2. Neural stem cell-derived neuronal survival protein

MTMRSLLRTPFLCGLLWAFCAPGARAEEPAASFSQPGSMGLDKNTVHDQEHIMEHLEGVI
NKPEAEMSPQELQLHYFKMHDYDGNNLLDGLELSTAITHVHKEEGSEQAPLMSEDELINI
IDGVLRDDDKNNDGYIDYAEFAKSLQ

• 1-26

• None

• Endoplasmic reticulum-Golgi intermediate compartment

ATGACCATGAGATCCCTGCTCAGAACCCCCTTCCTGTGTGGCCTGCTCTGGGCCTTTTGT
GCCCCAGGCGCCAGGGCTGAGGAGCCTGCAGCCAGCTTCTCCCAACCCGGCAGCATGGGC
CTGGATAAGAACACAGTGCACGACCAAGAGCATATCATGGAGCATCTAGAAGGTGTCATC
AACAAACCAGAGGCGGAGATGTCGCCACAAGAATTGCAGCTCCATTACTTCAAAATGCAT
GATTATGATGGCAATAATTTGCTTGATGGCTTAGAACTCTCCACAGCCATCACTCATGTC
CATAAGGAGGAAGGGAGTGAACAGGCACCACTAATGAGTGAAGATGAACTGATTAACATA
ATAGATGGTGTTTTGAGAGATGATGACAAGAACAATGATGGATACATTGACTATGCTGAA
TTTGCAAAATCACTGCAGTAG

1. [PubMed ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
3. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]