Showing drug card for Carvedilol (DB01136)

• APRD00091

• Approved
• Investigational
• Small Molecule

1. Carvedilolum [Latin]
2. carvedilol

1. Coreg

• Show PDF (issued on 2001-11-01)

• Show PDF

• Adrenergic Agents
• Adrenergic alpha-Antagonists
• Adrenergic beta-Antagonists
• Antihypertensive Agents
• Vasodilator Agents

• C07AG02

• 24:04.00
• 24:24.00

• Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).

1. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. [PubMed ]
2. Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL: Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002 Oct 22;106(17):2194-9. [PubMed ]
3. Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. [PubMed ]
4. Drugs.com
5. Wikipedia
6. RxList

• Humans and other mammals

1. Cytochrome P450 2C9 (CYP2C9)
2. Xanthine dehydrogenase/oxidase
3. Cytochrome P450 2D6 (CYP2D6)

1. Potassium voltage-gated channel subfamily H member 2
2. Vascular endothelial growth factor A
3. Beta-1 adrenergic receptor
4. NADH dehydrogenase [ubiquinone] 1 subunit C2
5. Alpha-1A adrenergic receptor
6. Beta-2 adrenergic receptor
7. Natriuretic peptides B
8. Multidrug resistance protein 1
9. Gap junction alpha-1 protein
10. Vascular cell adhesion protein 1

MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV

TADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCGEGGCGACTVMLSKYDRL
QNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQERIAKSHGSQCGFCTPGIV
MSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGFRTFARDGGCCGGDGNNPNCCM
NQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLRLKDTPRKQLRFEGERVTWIQAST
LKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFPMIVCPAWIPELNSVEHGPDGISFGA
ACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQLRWFAGKQVKSVASVGGNIITASPISDL
NPVFMASGAKLTLVSRGTRRTVQMDHTFFPGYRKTLLSPEEILLSIEIPYSREGEYFSAF
KQASRREDDIAKVTSGMRVLFKPGTTEVQELALCYGGMANRTISALKTTQRQLSKLWKEE
LLQDVCAGLAEELHLPPDAPGGMVDFRCTLTLSFFFKFYLTVLQKLGQENLEDKCGKLDP
TFASATLLFQKDPPADVQLFQEVPKGQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRYE
NELSLRLVTSTRAHAKIKSIDTSEAKKVPGFVCFISADDVPGSNITGICNDETVFAKDKV
TCVGHIIGAVVADTPEHTQRAAQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDLK
KGFSEADNVVSGEIYIGGQEHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKML
GVPANRIVVRVKRMGGGFGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGRH
PFLARYKVGFMKTGTVVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGRL
CKTNLPSNTAFRGFGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKLE
GFTLPRCWEECLASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGAL
LHVYTDGSVLLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAAS
VSADLNGQAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLGY
SFETNSGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAFV
QGLGLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAVG
EPPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVTG
VPENCKPWSVRV

MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR

1. Eag-related protein 1
2. Erg1
3. Ether-a-go-go-related gene potassium channel 1
4. Ether-a-go-go-related protein 1
5. H-ERG
6. Voltage-gated potassium channel subunit Kv11.1
7. eag homolog

MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVM
QRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDG
AVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSV
RSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSP
PRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPP
RHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIA
PKIKERTHNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIY
TAVFTPYSAAFLLKETEEGPPATECGYACQPLAVVDLIVDIMFIVDILINFRTTYVNANE
EVVSHPGRIAVHYFKGWFLIDMVAAIPFDLLIFGSGSEELIGLLKTARLLRLVRVARKLD
RYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSS
GLGGPSIKDKYVTALYFTFSSLTSVGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVS
AIIQRLYSGTARYHTQMLRVREFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGF
PECLQADICLHLNRSLLQHCKPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALY
FISRGSIEILRGDVVVAILGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLE
VLDMYPEFSDHFWSSLEITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTE
QPGEVSALGPGRAGAGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSS
PRPPGEPPGGEPLMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTP
SLLNIPLSSPGRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSA
VTTPGPGPTSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPG
QLGALTSQPLHRHGSDPGS

• cNMP_binding (PF00027 )
• Ion_trans (PF00520 )
• PAS (PF00989 )

• None

• 404-424
• 451-471
• 496-516
• 521-541
• 548-568
• 639-659

• Membrane
• multi-pass membrane protein

ATGCCGGTGCGGAGGGGCCACGTCGCGCCGCAGAACACCTTCCTGGACACCATCATCCGC
AAGTTTGAGGGCCAGAGCCGTAAGTTCATCATCGCCAACGCTCGGGTGGAGAACTGCGCC
GTCATCTACTGCAACGACGGCTTCTGCGAGCTGTGCGGCTACTCGCGGGCCGAGGTGATG
CAGCGACCCTGCACCTGCGACTTCCTGCACGGGCCGCGCACGCAGCGCCGCGCTGCCGCG
CAGATCGCGCAGGCACTGCTGGGCGCCGAGGAGCGCAAAGTGGAAATCGCCTTCTACCGG
AAAGATGGGAGCTGCTTCCTATGTCTGGTGGATGTGGTGCCCGTGAAGAACGAGGATGGG
GCTGTCATCATGTTCATCCTCAATTTCGAGGTGGTGATGGAGAAGGACATGGTGGGGTCC
CCGGCTCATGACACCAACCACCGGGGCCCCCCCACCAGCTGGCTGGCCCCAGGCCGCGCC
AAGACCTTCCGCCTGAAGCTGCCCGCGCTGCTGGCGCTGACGGCCCGGGAGTCGTCGGTG
CGGTCGGGCGGCGCGGGCGGCGCGGGCGCCCCGGGGGCCGTGGTGGTGGACGTGGACCTG
ACGCCCGCGGCACCCAGCAGCGAGTCGCTGGCCCTGGACGAAGTGACAGCCATGGACAAC
CACGTGGCAGGGCTCGGGCCCGCGGAGGAGCGGCGTGCGCTGGTGGGTCCCGGCTCTCCG
CCCCGCAGCGCGCCCGGCCAGCTCCCATCGCCCCGGGCGCACAGCCTCAACCCCGACGCC
TCGGGCTCCAGCTGCAGCCTGGCCCGGACGCGCTCCCGAGAAAGCTGCGCCAGCGTGCGC
CGCGCCTCGTCGGCCGACGACATCGAGGCCATGCGCGCCGGGGTGCTGCCCCCGCCACCG
CGCCACGCCAGCACCGGGGCCATGCACCCACTGCGCAGCGGCTTGCTCAACTCCACCTCG
GACTCCGACCTCGTGCGCTACCGCACCATTAGCAAGATTCCCCAAATCACCCTCAACTTT
GTGGACCTCAAGGGCGACCCCTTCTTGGCTTCGCCCACCAGTGACCGTGAGATCATAGCA
CCTAAGATAAAGGAGCGAACCCACAATGTCACTGAGAAGGTCACCCAGGTCCTGTCCCTG
GGCGCCGACGTGCTGCCTGAGTACAAGCTGCAGGCACCGCGCATCCACCGCTGGACCATC
CTGCATTACAGCCCCTTCAAGGCCGTGTGGGACTGGCTCATCCTGCTGCTGGTCATCTAC
ACGGCTGTCTTCACACCCTACTCGGCTGCCTTCCTGCTGAAGGAGACGGAAGAAGGCCCG
CCTGCTACCGAGTGTGGCTACGCCTGCCAGCCGCTGGCTGTGGTGGACCTCATCGTGGAC
ATCATGTTCATTGTGGACATCCTCATCAACTTCCGCACCACCTACGTCAATGCCAACGAG
GAGGTGGTCAGCCACCCCGGCCGCATCGCCGTCCACTACTTCAAGGGCTGGTTCCTCATC
GACATGGTGGCCGCCATCCCCTTCGACCTGCTCATCTTCGGCTCTGGCTCTGAGGAGCTG
ATCGGGCTGCTGAAGACTGCGCGGCTGCTGCGGCTGGTGCGCGTGGCGCGGAAGCTGGAT
CGCTACTCAGAGTACGGCGCGGCCGTGCTGTTCTTGCTCATGTGCACCTTTGCGCTCATC
GCGCACTGGCTAGCCTGCATCTGGTACGCCATCGGCAACATGGAGCAGCCACACATGGAC
TCACGCATCGGCTGGCTGCACAACCTGGGCGACCAGATAGGCAAACCCTACAACAGCAGC
GGCCTGGGCGGCCCCTCCATCAAGGACAAGTATGTGACGGCGCTCTACTTCACCTTCAGC
AGCCTCACCAGTGTGGGCTTCGGCAACGTCTCTCCCAACACCAACTCAGAGAAGATCTTC
TCCATCTGCGTCATGCTCATTGGCTCCCTCATGTATGCTAGCATCTTCGGCAACGTGTCG
GCCATCATCCAGCGGCTGTACTCGGGCACAGCCCGCTACCACACACAGATGCTGCGGGTG
CGGGAGTTCATCCGCTTCCACCAGATCCCCAATCCCCTGCGCCAGCGCCTCGAGGAGTAC
TTCCAGCACGCCTGGTCCTACACCAACGGCATCGACATGAACGCGGTGCTGAAGGGCTTC
CCTGAGTGCCTGCAGGCTGACATCTGCCTGCACCTGAACCGCTCACTGCTGCAGCACTGC
AAACCCTTCCGAGGGGCCACCAAGGGCTGCCTTCGGGCCCTGGCCATGAAGTTCAAGACC
ACACATGCACCGCCAGGGGACACACTGGTGCATGCTGGGGACCTGCTCACCGCCCTGTAC
TTCATCTCCCGGGGCTCCATCGAGATCCTGCGGGGCGACGTCGTCGTGGCCATCCTGGGG
AAGAATGACATCTTTGGGGAGCCTCTGAACCTGTATGCAAGGCCTGGCAAGTCGAACGGG
GATGTGCGGGCCCTCACCTACTGTGACCTACACAAGATCCATCGGGACGACCTGCTGGAG
GTGCTGGACATGTACCCTGAGTTCTCCGACCACTTCTGGTCCAGCCTGGAGATCACCTTC
AACCTGCGAGATACCAACATGATCCCGGGCTCCCCCGGCAGTACGGAGTTAGAGGGTGGC
TTCAGTCGGCAACGCAAGCGCAAGTTGTCCTTCCGCAGGCGCACGGACAAGGACACGGAG
CAGCCAGGGGAGGTGTCGGCCTTGGGGCCGGGCCGGGCGGGGGCAGGGCCGAGTAGCCGG
GGCCGGCCGGGGGGGCCGTGGGGGGAGAGCCCGTCCAGTGGCCCCTCCAGCCCTGAGAGC
AGTGAGGATGAGGGCCCAGGCCGCAGCTCCAGCCCCCTCCGCCTGGTGCCCTTCTCCAGC
CCCAGGCCCCCCGGAGAGCCGCCGGGTGGGGAGCCCCTGATGGAGGACTGCGAGAAGAGC
AGCGACACTTGCAACCCCCTGTCAGGCGCCTTCTCAGGAGTGTCCAACATTTTCAGCTTC
TGGGGGGACAGTCGGGGCCGCCAGTACCAGGAGCTCCCTCGATGCCCCGCCCCCACCCCC
AGCCTCCTCAACATCCCCCTCTCCAGCCCGGGTCGGCGGCCCCGGGGCGACGTGGAGAGC
AGGCTGGATGCCCTCCAGCGCCAGCTCAACAGGCTGGAGACCCGGCTGAGTGCAGACATG
GCCACTGTCCTGCAGCTGCTACAGAGGCAGATGACGCTGGTCCCGCCCGCCTACAGTGCT
GTGACCACCCCGGGGCCTGGCCCCACTTCCACATCCCCGCTGTTGCCCGTCAGCCCCCTC
CCCACCCTCACCTTGGACTCGCTTTCTCAGGTTTCCCAGTTCATGGCGTGTGAGGAGCTG
CCCCCGGGGGCCCCAGAGCTTCCCCAAGAAGGCCCCACACGACGCCTCTCCCTACCGGGC
CAGCTGGGGGCCCTCACCTCCCAGCCCCTGCACAGACACGGCTCGGACCCGGGCAGTTAG

1. Berthet M, Denjoy I, Donger C, Demay L, Hammoude H, Klug D, Schulze-Bahr E, Richard P, Funke H, Schwartz K, Coumel P, Hainque B, Guicheney P: C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence. Circulation. 1999 Mar 23;99(11):1464-70. [PubMed ]
2. Chen J, Zou A, Splawski I, Keating MT, Sanguinetti MC: Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. J Biol Chem. 1999 Apr 9;274(15):10113-8. [PubMed ]
3. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA: MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999 Apr 16;97(2):175-87. [PubMed ]
4. Jongbloed RJ, Wilde AA, Geelen JL, Doevendans P, Schaap C, Van Langen I, van Tintelen JP, Cobben JM, Beaufort-Krol GC, Geraedts JP, Smeets HJ: Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999;13(4):301-10. [PubMed ]
5. Yoshida H, Horie M, Otani H, Takano M, Tsuji K, Kubota T, Fukunami M, Sasayama S: Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome. J Cardiovasc Electrophysiol. 1999 Sep;10(9):1262-70. [PubMed ]
6. Larsen LA, Svendsen IH, Jensen AM, Kanters JK, Andersen PS, Moller M, Sorensen SA, Sandoe E, Jacobsen JR, Vuust J, Christiansen M: Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2. Clin Genet. 2000 Feb;57(2):125-30. [PubMed ]
7. Paulussen A, Yang P, Pangalos M, Verhasselt P, Marrannes R, Verfaille C, Vandenberk I, Crabbe R, Konings F, Luyten W, Armstrong M: Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion. Hum Mutat. 2000 May;15(5):483. [PubMed ]
8. Cui J, Melman Y, Palma E, Fishman GI, McDonald TV: Cyclic AMP regulates the HERG K(+) channel by dual pathways. Curr Biol. 2000 Jun 1;10(11):671-4. [PubMed ]
9. Laitinen P, Fodstad H, Piippo K, Swan H, Toivonen L, Viitasalo M, Kaprio J, Kontula K: Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat. 2000 Jun;15(6):580-1. [PubMed ]
10. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed ]
11. 11374908 Soejima H, Kawamoto S, Akai J, Miyoshi O, Arai Y, Morohka T, Matsuo S, Niikawa N, Kimura A, Okubo K, Mukai T: Isolation of novel heart-specific genes using the BodyMap database. Genomics. 2001 May 15;74(1):115-20.
12. 12062363 Hayashi K, Shimizu M, Ino H, Yamaguchi M, Mabuchi H, Hoshi N, Higashida H: Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG in a patient with long QT syndrome. Cardiovasc Res. 2002 Apr;54(1):67-76.
13. 12063277 Gong Q, Anderson CL, January CT, Zhou Z: Role of glycosylation in cell surface expression and stability of HERG potassium channels. Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H77-84.
14. 7889573 Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995 Mar 10;80(5):795-803.
15. 8159766 Warmke JW, Ganetzky B: A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3438-42.
16. 8635257 Benson DW, MacRae CA, Vesely MR, Walsh EP, Seidman JG, Seidman CE, Satler CA: Missense mutation in the pore region of HERG causes familial long QT syndrome. Circulation. 1996 May 15;93(10):1791-5.
17. 8877771 Dausse E, Berthet M, Denjoy I, Andre-Fouet X, Cruaud C, Bennaceur M, Faure S, Coumel P, Schwartz K, Guicheney P: A mutation in HERG associated with notched T waves in long QT syndrome. J Mol Cell Cardiol. 1996 Aug;28(8):1609-15.
18. 8914737 Satler CA, Walsh EP, Vesely MR, Plummer MH, Ginsburg GS, Jacob HJ: Novel missense mutation in the cyclic nucleotide-binding domain of HERG causes long QT syndrome. Am J Med Genet. 1996 Oct 2;65(1):27-35.
19. 9024139 Tanaka T, Nagai R, Tomoike H, Takata S, Yano K, Yabuta K, Haneda N, Nakano O, Shibata A, Sawayama T, Kasai H, Yazaki Y, Nakamura Y: Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation. 1997 Feb 4;95(3):565-7.
20. 9230439 McDonald TV, Yu Z, Ming Z, Palma E, Meyers MB, Wang KW, Goldstein SA, Fishman GI: A minK-HERG complex regulates the cardiac potassium current I(Kr). Nature. 1997 Jul 17;388(6639):289-92.
21. 9351446 Lees-Miller JP, Kondo C, Wang L, Duff HJ: Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts. Circ Res. 1997 Nov;81(5):719-26.
22. 9351462 London B, Trudeau MC, Newton KP, Beyer AK, Copeland NG, Gilbert DJ, Jenkins NA, Satler CA, Robertson GA: Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current. Circ Res. 1997 Nov;81(5):870-8.
23. 9452080 Akimoto K, Furutani M, Imamura S, Furutani Y, Kasanuki H, Takao A, Momma K, Matsuoka R: Novel missense mutation (G601S) of HERG in a Japanese long QT syndrome family. Hum Mutat. 1998;Suppl 1:S184-6.
24. 9544837 Satler CA, Vesely MR, Duggal P, Ginsburg GS, Beggs AH: Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. Hum Genet. 1998 Mar;102(3):265-72.
25. 9600240 Itoh T, Tanaka T, Nagai R, Kamiya T, Sawayama T, Nakayama T, Tomoike H, Sakurada H, Yazaki Y, Nakamura Y: Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome. Hum Genet. 1998 Apr;102(4):435-9.
26. 9693036 Splawski I, Shen J, Timothy KW, Vincent GM, Lehmann MH, Keating MT: Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998 Jul 1;51(1):86-97.
27. 9765245 Kupershmidt S, Snyders DJ, Raes A, Roden DM: A K+ channel splice variant common in human heart lacks a C-terminal domain required for expression of rapidly activating delayed rectifier current. J Biol Chem. 1998 Oct 16;273(42):27231-5.
28. 9845367 Morais Cabral JH, Lee A, Cohen SL, Chait BT, Li M, Mackinnon R: Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell. 1998 Nov 25;95(5):649-55.

1. Karle CA, Kreye VA, Thomas D, Rockl K, Kathofer S, Zhang W, Kiehn J: Antiarrhythmic drug carvedilol inhibits HERG potassium channels. Cardiovasc Res. 2001 Feb 1;49(2):361-70. [PubMed ]
2. Kawakami K, Nagatomo T, Abe H, Kikuchi K, Takemasa H, Anson BD, Delisle BP, January CT, Nakashima Y: Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. [PubMed ]

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

MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR

• PDGF (PF00341 )

• 1-26

• None

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

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

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

1. de Boer RA, Siebelink HJ, Tio RA, Boomsma F, van Veldhuisen DJ: Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure. Eur J Heart Fail. 2001 Jun;3(3):331-3. [PubMed ]
2. Saijonmaa O, Nyman T, Fyhrquist F: Carvedilol inhibits basal and stimulated ACE production in human endothelial cells. J Cardiovasc Pharmacol. 2004 May;43(5):616-21. [PubMed ]
3. Shyu KG, Lu MJ, Chang H, Sun HY, Wang BW, Kuan P: Carvedilol modulates the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of volume-overload heart failure. J Card Fail. 2005 Mar;11(2):152-9. [PubMed ]
4. Shyu KG, Liou JY, Wang BW, Fang WJ, Chang H: Carvedilol prevents cardiac hypertrophy and overexpression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in pressure-overloaded rat heart. J Biomed Sci. 2005;12(2):409-20. [PubMed ]

1. Beta-1 adrenoceptor
2. Beta-1 adrenoreceptor

MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAG
MGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVV
WGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVC
TVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIM
AFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAP
LANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFV
FFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGP
PPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV

• 7tm_1 (PF00001 )

• None

• 60-83
• 97-120
• 132-155
• 176-199
• 222-245
• 326-349
• 357-380

• Cell membrane
• multi-pass membrane protein. Localized at the plasma membrane. Found in the Golgi upo

ATGGGCGCGGGGGTGCTCGTCCTGGGCGCCTCCGAGCCCGGTAACCTGTCGTCGGCCGCA
CCGCTCCCCGACGGCGCGGCCACCGCGGCGCGGCTGCTGGTGCCCGCGTCGCCGCCCGCC
TCGTTGCTGCCTCCCGCCAGCGAAAGCCCCGAGCCGCTGTCTCAGCAGTGGACAGCGGGC
ATGGGTCTGCTGATGGCGCTCATCGTGCTGCTCATCGTGGCGGGCAATGTGCTGGTGATC
GTGGCCATCGCCAAGACGCCGCGGCTGCAGACGCTCACCAACCTCTTCATCATGTCCCTG
GCCAGCGCCGACCTGGTCATGGGGCTGCTGGTGGTGCCGTTCGGGGCCACCATCGTGGTG
TGGGGCCGCTGGGAGTACGGCTCCTTCTTCTGCGAGCTGTGGACCTCAGTGGACGTGCTG
TGCGTGACGGCCAGCATCGAGACCCTGTGTGTCATTGCCCTGGACCGCTACCTCGCCATC
ACCTCGCCCTTCCGCTACCAGAGCCTGCTGACGCGCGCGCGGGCGCGGGGCCTCGTGTGC
ACCGTGTGGGCCATCTCGGCCCTGGTGTCCTTCCTGCCCATCCTCATGCACTGGTGGCGG
GCGGAGAGCGACGAGGCGCGCCGCTGCTACAACGACCCCAAGTGCTGCGACTTCGTCACC
AACCGGGCCTACGCCATCGCCTCGTCCGTAGTCTCCTTCTACGTGCCCCTGTGCATCATG
GCCTTCGTGTACCTGCGGGTGTTCCGCGAGGCCCAGAAGCAGGTGAAGAAGATCGACAGC
TGCGAGCGCCGTTTCCTCGGCGGCCCAGCGCGGCCGCCCTCGCCCTCGCCCTCGCCCGTC
CCCGCGCCCGCGCCGCCGCCCGGACCCCCGCGCCCCGCCGCCGCCGCCGCCACCGCCCCG
CTGGCCAACGGGCGTGCGGGTAAGCGGCGGCCCTCGCGCCTCGTGGCCCTACGCGAGCAG
AAGGCGCTCAAGACGCTGGGCATCATCATGGGCGTCTTCACGCTCTGCTGGCTGCCCTTC
TTCCTGGCCAACGTGGTGAAGGCCTTCCACCGCGAGCTGGTGCCCGACCGCCTCTTCGTC
TTCTTCAACTGGCTGGGCTACGCCAACTCGGCCTTCAACCCCATCATCTACTGCCGCAGC
CCCGACTTCCGCAAGGCCTTCCAGGGACTGCTCTGCTGCGCGCGCAGGGCTGCCCGCCGG
CGCCACGCGACCCACGGAGACCGGCCGCGCGCCTCGGGCTGTCTGGCCCGGCCCGGACCC
CCGCCATCGCCCGGGGCCGCCTCGGACGACGACGACGACGATGTCGTCGGGGCCACGCCG
CCCGCGCGCCTGCTGGAGCCCTGGGCCGGCTGCAACGGCGGGGCGGCGGCGGACAGCGAC
TCGAGCCTGGACGAGCCGTGCCGCCCCGGCTTCGCCTCGGAATCCAAGGTGTAG

1. Mason DA, Moore JD, Green SA, Liggett SB: A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. [PubMed ]
2. Moore JD, Mason DA, Green SA, Hsu J, Liggett SB: Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999 Sep 19;14(3):271. [PubMed ]
3. Borjesson M, Magnusson Y, Hjalmarson A, Andersson B: A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J. 2000 Nov;21(22):1853-8. [PubMed ]
4. Ranade K, Jorgenson E, Sheu WH, Pei D, Hsiung CA, Chiang FT, Chen YD, Pratt R, Olshen RA, Curb D, Cox DR, Botstein D, Risch N: A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002 Apr;70(4):935-42. Epub 2002 Feb 18. [PubMed ]
5. Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK: Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920-4. [PubMed ]

1. Nichols AJ, Gellai M, Ruffolo RR Jr: Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. [PubMed ]
2. Nichols AJ, Sulpizio AC, Ashton DJ, Hieble JP, Ruffolo RR Jr: In vitro pharmacologic profile of the novel beta-adrenoceptor antagonist and vasodilator, carvedilol. Pharmacology. 1989;39(5):327-36. [PubMed ]
3. Nichols AJ, Sulpizio AC, Ashton DJ, Hieble JP, Ruffolo RR Jr: The interaction of the enantiomers of carvedilol with alpha 1- and beta 1-adrenoceptors. Chirality. 1989;1(4):265-70. [PubMed ]
4. de Mey C, Breithaupt K, Schloos J, Neugebauer G, Palm D, Belz GG: Dose-effect and pharmacokinetic-pharmacodynamic relationships of the beta 1-adrenergic receptor blocking properties of various doses of carvedilol in healthy humans. Clin Pharmacol Ther. 1994 Mar;55(3):329-37. [PubMed ]

1. CI-B14.5b
2. Complex I-B14.5b
3. EC 1.6.5.3
4. EC 1.6.99.3
5. NADH-ubiquinone oxidoreductase subunit B14.5b

MIARRNPEPLRFLPDEARSLPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQ
LLYITAFFFAGYYLVKREDYLYAVRDREMFGYMKLHPEDFPEEDKKTYGEIFEKFHPIR

• NADH + H+ + ubiquinone = NAD+ + ubiquinol

• NDUF_C2 (PF06374 )

• None

• 56-75

• Mitochondrion
• matrix side
• mitochondrial inner membrane

ATGATCGCACGGCGGAACCCAGAACCCTTACGGTTTCTGCCGGATGAGGCCCGGAGCCTG
CCCCCGCCCAAGCTGACCGACCCGCGGCTCCTCTACATCGGCTTCTTGGGCTACTGCTCC
GGCCTGATTGATAACCTGATCCGGCGGAGGCCGATCGCGACGGCTGGTTTGCATCGCCAG
CTTCTATATATTACGGCCTTTTTTTTTGCTGGATATTATCTTGTAAAACGTGAAGACTAC
CTGTATGCTGTGAGGGACCGTGAAATGTTTGGATATATGAAATTACATCCAGAGGATTTT
CCTGAAGAAGATAAGAAAACATATGGTGAAATTTTTGAAAAATTCCATCCAATACGTTGA

1. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome Res. 2000 Oct;10(10):1546-60. [PubMed ]
2. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. [PubMed ]
3. Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA: cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed. Biochem Biophys Res Commun. 1998 Dec 18;253(2):415-22. [PubMed ]

1. Oliveira PJ, Santos DJ, Moreno AJ: Carvedilol inhibits the exogenous NADH dehydrogenase in rat heart mitochondria. Arch Biochem Biophys. 2000 Feb 15;374(2):279-85. [PubMed ]

1. Alpha 1A- adrenoreceptor
2. Alpha 1A-adrenoceptor
3. Alpha adrenergic receptor 1c
4. Alpha-1C adrenergic receptor

MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSV
THYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCII
SIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINE
EPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKN
APAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPD
FKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTL
HPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCT
TARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV

• 7tm_1 (PF00001 )

• None

• 28-51
• 65-88
• 100-122
• 144-167
• 182-205
• 274-297
• 306-329

• Membrane
• multi-pass membrane protein

ATGGTGTTTCTCTCGGGAAATGCTTCCGACAGCTCCAACTGCACCCAACCGCCGGCACCG
GTGAACATTTCCAAGGCCATTCTGCTCGGGGTGATCTTGGGGGGCCTCATTCTTTTCGGG
GTGCTGGGTAACATCCTAGTGATCCTCTCCGTAGCCTGTCACCGACACCTGCACTCAGTC
ACGCACTACTACATCGTCAACCTGGCGGTGGCCGACCTCCTGCTCACCTCCACGGTGCTG
CCCTTCTCCGCCATCTTCGAGGTCCTAGGCTACTGGGCCTTCGGCAGGGTCTTCTGCAAC
ATCTGGGCGGCAGTGGATGTGCTGTGCTGCACCGCGTCCATCATGGGCCTCTGCATCATC
TCCATCGACCGCTACATCGGCGTGAGCTACCCGCTGCGCTACCCAACCATCGTCACCCAG
AGGAGGGGTCTCATGGCTCTGCTCTGCGTCTGGGCACTCTCCCTGGTCATATCCATTGGA
CCCCTGTTCGGCTGGAGGCAGCCGGCCCCCGAGGACGAGACCATCTGCCAGATCAACGAG
GAGCCGGGCTACGTGCTCTTCTCAGCGCTGGGCTCCTTCTACCTGCCTCTGGCCATCATC
CTGGTCATGTACTGCCGCGTCTACGTGGTGGCCAAGAGGGAGAGCCGGGGCCTCAAGTCT
GGCCTCAAGACCGACAAGTCGGACTCGGAGCAAGTGACGCTCCGCATCCATCGGAAAAAC
GCCCCGGCAGGAGGCAGCGGGATGGCCAGCGCCAAGACCAAGACGCACTTCTCAGTGAGG
CTCCTCAAGTTCTCCCGGGAGAAGAAAGCGGCCAAAACGCTGGGCATCGTGGTCGGCTGC
TTCGTCCTCTGCTGGCTGCCTTTTTTCTTAGTCATGCCCATTGGGTCTTTCTTCCCTGAT
TTCAAGCCCTCTGAAACAGTTTTTAAAATAGTATTTTGGCTCGGATATCTAAACAGCTGC
ATCAACCCCATCATATACCCATGCTCCAGCCAAGAGTTCAAAAAGGCCTTTCAGAATGTC
TTGAGAATCCAGTGTCTCCGCAGAAAGCAGTCTTCCAAACATGCCCTGGGCTACACCCTG
CACCCGCCCAGCCAGGCCGTGGAAGGGCAACACAAGGACATGGTGCGCATCCCCGTGGGA
TCAAGAGAGACCTTCTACAGGATCTCCAAGACGGATGGCGTTTGTGAATGGAAATTTTTC
TCTTCCATGCCCCGTGGATCTGCCAGGATTACAGTGTCCAAAGACCAATCCTCCTGTACC
ACAGCCCGGGTGAGAAGTAAAAGCTTTTTGGAGGTCTGCTGCTGTGTAGGGCCCTCAACC
CCCAGCCTTGACAAGAACCATCAAGTTCCAACCATTAAGGTCCACACCATCTCCCTCAGT
GAGAACGGGGAGGAAGTCTAG

1. Hirasawa A, Shibata K, Horie K, Takei Y, Obika K, Tanaka T, Muramoto N, Takagaki K, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants. FEBS Lett. 1995 Apr 24;363(3):256-60. [PubMed ]
2. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed ]
3. Weinberg DH, Trivedi P, Tan CP, Mitra S, Perkins-Barrow A, Borkowski D, Strader CD, Bayne M: Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c. Biochem Biophys Res Commun. 1994 Jun 30;201(3):1296-304. [PubMed ]
4. Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed ]
5. Hirasawa A, Horie K, Tanaka T, Takagaki K, Murai M, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Biochem Biophys Res Commun. 1993 Sep 15;195(2):902-9. [PubMed ]
6. Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, Godinot N, Robertson CN, Saussy D: The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475-85. [PubMed ]
7. Chang DJ, Chang TK, Yamanishi SS, Salazar FH, Kosaka AH, Khare R, Bhakta S, Jasper JR, Shieh IS, Lesnick JD, Ford AP, Daniels DV, Eglen RM, Clarke DE, Bach C, Chan HW: Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. 1998 Jan 30;422(2):279-83. [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. Beta-2 adrenoceptor
2. Beta-2 adrenoreceptor

MGQPGNGSAFLLAPNRSHAPDHDVTQQRDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL

• 7tm_1 (PF00001 )

• None

• 35-58
• 72-95
• 107-129
• 151-174
• 197-220
• 275-298
• 306-329

• Membrane
• multi-pass membrane protein

ATGGGGCAACCCGGGAACGGCAGCGCCTTCTTGCTGGCACCCAATAGAAGCCATGCGCCG
GACCACGACGTCACGCAGCAAAGGGACGAGGTGTGGGTGGTGGGCATGGGCATCGTCATG
TCTCTCATCGTCCTGGCCATCGTGTTTGGCAATGTGCTGGTCATCACAGCCATTGCCAAG
TTCGAGCGTCTGCAGACGGTCACCAACTACTTCATCACTTCACTGGCCTGTGCTGATCTG
GTCATGGGCCTGGCAGTGGTGCCCTTTGGGGCCGCCCATATTCTTATGAAAATGTGGACT
TTTGGCAACTTCTGGTGCGAGTTTTGGACTTCCATTGATGTGCTGTGCGTCACGGCCAGC
ATTGAGACCCTGTGCGTGATCGCAGTGGATCGCTACTTTGCCATTACTTCACCTTTCAAG
TACCAGAGCCTGCTGACCAAGAATAAGGCCCGGGTGATCATTCTGATGGTGTGGATTGTG
TCAGGCCTTACCTCCTTCTTGCCCATTCAGATGCACTGGTACCGGGCCACCCACCAGGAA
GCCATCAACTGCTATGCCAATGAGACCTGCTGTGACTTCTTCACGAACCAAGCCTATGCC
ATTGCCTCTTCCATCGTGTCCTTCTACGTTCCCCTGGTGATCATGGTCTTCGTCTACTCC
AGGGTCTTTCAGGAGGCCAAAAGGCAGCTCCAGAAGATTGACAAATCTGAGGGCCGCTTC
CATGTCCAGAACCTTAGCCAGGTGGAGCAGGATGGGCGGACGGGGCATGGACTCCGCAGA
TCTTCCAAGTTCTGCTTGAAGGAGCACAAAGCCCTCAAGACGTTAGGCATCATCATGGGC
ACTTTCACCCTCTGCTGGCTGCCCTTCTTCATCGTTAACATTGTGCATGTGATCCAGGAT
AACCTCATCCGTAAGGAAGTTTACATCCTCCTAAATTGGATAGGCTATGTCAATTCTGGT
TTCAATCCCCTTATCTACTGCCGGAGCCCAGATTTCAGGATTGCCTTCCAGGAGCTTCTG
TGCCTGCGCAGGTCTTCTTTGAAGGCCTATGGGAATGGCTACTCCAGCAACGGCAACACA
GGGGAGCAGAGTGGATATCACGTGGAACAGGAGAAAGAAAATAAACTGCTGTGTGAAGAC
CTCCCAGGCACGGAAGACTTTGTGGGCCATCAAGGTACTGTGCCTAGCGATAACATTGAT
TCACAAGGGAGGAATTGTAGTACAAATGACTCACTGCTGTAA

1. Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M: A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. [PubMed ]
2. Moffett S, Rousseau G, Lagace M, Bouvier M: The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization. J Neurochem. 2001 Jan;76(1):269-79. [PubMed ]
3. O'Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M: Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem. 1989 May 5;264(13):7564-9. [PubMed ]
4. Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD: Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):6995-9. [PubMed ]
5. Chung FZ, Wang CD, Potter PC, Venter JC, Fraser CM: Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. J Biol Chem. 1988 Mar 25;263(9):4052-5. [PubMed ]
6. Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ: cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci U S A. 1987 Jan;84(1):46-50. [PubMed ]
7. Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC: Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. FEBS Lett. 1987 Jan 26;211(2):200-6. [PubMed ]
8. Schofield PR, Rhee LM, Peralta EG: Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res. 1987 Apr 24;15(8):3636. [PubMed ]
9. Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RA, Keller P, Caron MG, Lefkowitz RJ: Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. J Biol Chem. 1987 May 25;262(15):7321-7. [PubMed ]
10. Turki J, Pak J, Green SA, Martin RJ, Liggett SB: Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest. 1995 Apr;95(4):1635-41. [PubMed ]
11. 7915137 Green SA, Turki J, Innis M, Liggett SB: Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994 Aug 16;33(32):9414-9.
12. 8383511 Reihsaus E, Innis M, MacIntyre N, Liggett SB: Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol. 1993 Mar;8(3):334-9.

1. Irodova NL, Krasnikova TL, Masenko VP, Kochetov AG, Chazova IE: [Carvedilol in treating primary pulmonary hypertension patients: effect on severity of cardiac failure, degree of pulmonary hypertension, concentration of catecholamines in blood plasma and dependence of cyclic AMP synthesis in lymphocytes on beta-adrenergic receptors] Ter Arkh. 2002;74(8):30-4. [PubMed ]
2. Maebara C, Ohtani H, Sugahara H, Mine K, Kubo C, Sawada Y: Nightmares and panic disorder associated with carvedilol overdose. Ann Pharmacother. 2002 Nov;36(11):1736-40. [PubMed ]
3. Okajima K, Harada N, Uchiba M, Isobe H: Activation of capsaicin-sensitive sensory neurons by carvedilol, a nonselective beta-blocker, in spontaneous hypertensive rats. J Pharmacol Exp Ther. 2004 May;309(2):684-91. Epub 2004 Feb 5. [PubMed ]
4. Nichols AJ, Gellai M, Ruffolo RR Jr: Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. [PubMed ]

1. Natriuretic peptides B precursor

MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVE
QTSLEPLQESPRPTGVWKSREVATEGIRGHRKMVLYTLRAPRSPKMVQGSGCFGRKMDRI
SSSSGLGCKVLRRH

• ANP (PF00212 )

• 1-26

• None

• Secreted protein

ATGGATCCCCAGACAGCACCTTCCCGGGCGCTCCTGCTCCTGCTCTTCTTGCATCTGGCT
TTCCTGGGAGGTCGTTCCCACCCGCTGGGCAGCCCCGGTTCAGCCTCGGACTTGGAAACG
TCCGGGTTACAGGAGCAGCGCAACCATTTGCAGGGCAAACTGTCGGAGCTGCAGGTGGAG
CAGACATCCCTGGAGCCCCTCCAGGAGAGCCCCCGTCCCACAGGTGTCTGGAAGTCCCGG
GAGGTAGCCACCGAGGGCATCCGTGGGCACCGCAAAATGGTCCTCTACACCCTGCGGGCA
CCACGAAGCCCCAAGATGGTGCAAGGGTCTGGCTGCTTTGGGAGGAAGATGGACCGGATC
AGCTCCTCCAGTGGCCTGGGCTGCAAAGTGCTGAGGCGGCATTAA

1. Kambayashi Y, Nakao K, Mukoyama M, Saito Y, Ogawa Y, Shiono S, Inouye K, Yoshida N, Imura H: Isolation and sequence determination of human brain natriuretic peptide in human atrium. FEBS Lett. 1990 Jan 1;259(2):341-5. [PubMed ]
2. Hino J, Tateyama H, Minamino N, Kangawa K, Matsuo H: Isolation and identification of human brain natriuretic peptides in cardiac atrium. Biochem Biophys Res Commun. 1990 Mar 16;167(2):693-700. [PubMed ]
3. Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H: Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1427-34. [PubMed ]
4. Seilhamer JJ, Arfsten A, Miller JA, Lundquist P, Scarborough RM, Lewicki JA, Porter JG: Human and canine gene homologs of porcine brain natriuretic peptide. Biochem Biophys Res Commun. 1989 Dec 15;165(2):650-8. [PubMed ]

1. Ohta Y, Watanabe K, Nakazawa M, Yamamoto T, Ma M, Fuse K, Ito M, Hirono S, Tanabe T, Hanawa H, Kato K, Kodama M, Aizawa Y: Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart. J Cardiovasc Pharmacol. 2000;36 Suppl 2:S19-23. [PubMed ]
2. Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J, Espiner EA, Frampton C, Yandle TG: Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol. 2001 Jun 1;37(7):1781-7. [PubMed ]
3. Konishi H, Nishio S, Tsutamoto T, Minouchi T, Yamaji A: Serum carvedilol concentration and its relation to change in plasma brain natriuretic peptide level in the treatment of heart failure: a preliminary study. Int J Clin Pharmacol Ther. 2003 Dec;41(12):578-86. [PubMed ]
4. Takeda Y, Fukutomi T, Suzuki S, Yamamoto K, Ogata M, Kondo H, Sugiura M, Shigeyama J, Itoh M: Effects of carvedilol on plasma B-type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction. Am J Cardiol. 2004 Aug 15;94(4):448-53. [PubMed ]
5. Frantz RP, Olson LJ, Grill D, Moualla SK, Nelson SM, Nobrega TP, Hanna RD, Backes RJ, Mookadam F, Heublein D, Bailey KR, Burnett JC: Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure. Am Heart J. 2005 Mar;149(3):541-7. [PubMed ]

1. ATP-binding cassette sub-family B member 1
2. CD243 antigen
3. EC 3.6.3.44
4. P-glycoprotein 1

MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSG
IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVS
KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFT
DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIG
AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARG
AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSG
QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLF
ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIA
IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAG
FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRS
SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAII
NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKA
GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNI
ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGAGKIATEA
IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDS
YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVV
QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVV
SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLD
EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQL
LAQKGIYFSMVSVQAGTKRQ

• ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout

• ABC_tran (PF00005 )
• ABC_membrane (PF00664 )

• None

• 52-72
• 120-140
• 189-209
• 216-236
• 297-317
• 326-346
• 711-731
• 757-777
• 833-853
• 854-874
• 937-957
• 974-994

• Membrane
• multi-pass membrane protein

ATGGATCTTGAAGGGGACCGCAATGGAGGAGCAAAGAAGAAGAACTTTTTTAAACTGAAC
AATAAAAGTGAAAAAGATAAGAAGGAAAAGAAACCAACTGTCAGTGTATTTTCAATGTTT
CGCTATTCAAATTGGCTTGACAAGTTGTATATGGTGGTGGGAACTTTGGCTGCCATCATC
CATGGGGCTGGACTTCCTCTCATGATGCTGGTGTTTGGAGAAATGACAGATATCTTTGCA
AATGCAGGAAATTTAGAAGATCTGATGTCAAACATCACTAATAGAAGTGATATCAATGAT
ACAGGGTTCTTCATGAATCTGGAGGAAGACATGACCAGGTATGCCTATTATTACAGTGGA
ATTGGTGCTGGGGTGCTGGTTGCTGCTTACATTCAGGTTTCATTTTGGTGCCTGGCAGCT
GGAAGACAAATACACAAAATTAGAAAACAGTTTTTTCATGCTATAATGCGACAGGAGATA
GGCTGGTTTGATGTGCACGATGTTGGGGAGCTTAACACCCGACTTACAGATGATGTCTCT
AAGATTAATGAAGTTATTGGTGACAAAATTGGAATGTTCTTTCAGTCAATGGCAACATTT
TTCACTGGGTTTATAGTAGGATTTACACGTGGTTGGAAGCTAACCCTTGTGATTTTGGCC
ATCAGTCCTGTTCTTGGACTGTCAGCTGCTGTCTGGGCAAAGATACTATCTTCATTTACT
GATAAAGAACTCTTAGCGTATGCAAAAGCTGGAGCAGTAGCTGAAGAGGTCTTGGCAGCA
ATTAGAACTGTGATTGCATTTGGAGGACAAAAGAAAGAACTTGAAAGGTACAACAAAAAT
TTAGAAGAAGCTAAAAGAATTGGGATAAAGAAAGCTATTACAGCCAATATTTCTATAGGT
GCTGCTTTCCTGCTGATCTATGCATCTTATGCTCTGGCCTTCTGGTATGGGACCACCTTG
GTCCTCTCAGGGGAATATTCTATTGGACAAGTACTCACTGTATTCTTTTCTGTATTAATT
GGGGCTTTTAGTGTTGGACAGGCATCTCCAAGCATTGAAGCATTTGCAAATGCAAGAGGA
GCAGCTTATGAAATCTTCAAGATAATTGATAATAAGCCAAGTATTGACAGCTATTCGAAG
AGTGGGCACAAACCAGATAATATTAAGGGAAATTTGGAATTCAGAAATGTTCACTTCAGT
TACCCATCTCGAAAAGAAGTTAAGATCTTGAAGGGCCTGAACCTGAAGGTGCAGAGTGGG
CAGACGGTGGCCCTGGTTGGAAACAGTGGCTGTGGGAAGAGCACAACAGTCCAGCTGATG
CAGAGGCTCTATGACCCCACAGAGGGGATGGTCAGTGTTGATGGACAGGATATTAGGACC
ATAAATGTAAGGTTTCTACGGGAAATCATTGGTGTGGTGAGTCAGGAACCTGTATTGTTT
GCCACCACGATAGCTGAAAACATTCGCTATGGCCGTGAAAATGTCACCATGGATGAGATT
GAGAAAGCTGTCAAGGAAGCCAATGCCTATGACTTTATCATGAAACTGCCTCATAAATTT
GACACCCTGGTTGGAGAGAGAGGGGCCCAGTTGAGTGGTGGGCAGAAGCAGAGGATCGCC
ATTGCACGTGCCCTGGTTCGCAACCCCAAGATCCTCCTGCTGGATGAGGCCACGTCAGCC
TTGGACACAGAAAGCGAAGCAGTGGTTCAGGTGGCTCTGGATAAGGCCAGAAAAGGTCGG
ACCACCATTGTGATAGCTCATCGTTTGTCTACAGTTCGTAATGCTGACGTCATCGCTGGT
TTCGATGATGGAGTCATTGTGGAGAAAGGAAATCATGATGAACTCATGAAAGAGAAAGGC
ATTTACTTCAAACTTGTCACAATGCAGACAGCAGGAAATGAAGTTGAATTAGAAAATGCA
GCTGATGAATCCAAAAGTGAAATTGATGCCTTGGAAATGTCTTCAAATGATTCAAGATCC
AGTCTAATAAGAAAAAGATCAACTCGTAGGAGTGTCCGTGGATCACAAGCCCAAGACAGA
AAGCTTAGTACCAAAGAGGCTCTGGATGAAAGTATACCTCCAGTTTCCTTTTGGAGGATT
ATGAAGCTAAATTTAACTGAATGGCCTTATTTTGTTGTTGGTGTATTTTGTGCCATTATA
AATGGAGGCCTGCAACCAGCATTTGCAATAATATTTTCAAAGATTATAGGGGTTTTTACA
AGAATTGATGATCCTGAAACAAAACGACAGAATAGTAACTTGTTTTCACTATTGTTTCTA
GCCCTTGGAATTATTTCTTTTATTACATTTTTCCTTCAGGGTTTCACATTTGGCAAAGCT
GGAGAGATCCTCACCAAGCGGCTCCGATACATGGTTTTCCGATCCATGCTCAGACAGGAT
GTGAGTTGGTTTGATGACCCTAAAAACACCACTGGAGCATTGACTACCAGGCTCGCCAAT
GATGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTGCTGTAATTACCCAGAATATA
GCAAATCTTGGGACAGGAATAATTATATCCTTCATCTATGGTTGGCAACTAACACTGTTA
CTCTTAGCAATTGTACCCATCATTGCAATAGCAGGAGTTGTTGAAATGAAAATGTTGTCT
GGACAAGCACTGAAAGATAAGAAAGAACTAGAAGGTGCTGGGAAGATCGCTACTGAAGCA
ATAGAAAACTTCCGAACCGTTGTTTCTTTGACTCAGGAGCAGAAGTTTGAACATATGTAT
GCTCAGAGTTTGCAGGTACCATACAGAAACTCTTTGAGGAAAGCACACATCTTTGGAATT
ACATTTTCCTTCACCCAGGCAATGATGTATTTTTCCTATGCTGGATGTTTCCGGTTTGGA
GCCTACTTGGTGGCACATAAACTCATGAGCTTTGAGGATGTTCTGTTAGTATTTTCAGCT
GTTGTCTTTGGTGCCATGGCCGTGGGGCAAGTCAGTTCATTTGCTCCTGACTATGCCAAA
GCCAAAATATCAGCAGCCCACATCATCATGATCATTGAAAAAACCCCTTTGATTGACAGC
TACAGCACGGAAGGCCTAATGCCGAACACATTGGAAGGAAATGTCACATTTGGTGAAGTT
GTATTCAACTATCCCACCCGACCGGACATCCCAGTGCTTCAGGGACTGAGCCTGGAGGTG
AAGAAGGGCCAGACGCTGGCTCTGGTGGGCAGCAGTGGCTGTGGGAAGAGCACAGTGGTC
CAGCTCCTGGAGCGGTTCTACGACCCCTTGGCAGGGAAAGTGCTGCTTGATGGCAAAGAA
ATAAAGCGACTGAATGTTCAGTGGCTCCGAGCACACCTGGGCATCGTGTCCCAGGAGCCC
ATCCTGTTTGACTGCAGCATTGCTGAGAACATTGCCTATGGAGACAACAGCCGGGTGGTG
TCACAGGAAGAGATCGTGAGGGCAGCAAAGGAGGCCAACATACATGCCTTCATCGAGTCA
CTGCCTAATAAATATAGCACTAAAGTAGGAGACAAAGGAACTCAGCTCTCTGGTGGCCAG
AAACAACGCATTGCCATAGCTCGTGCCCTTGTTAGACAGCCTCATATTTTGCTTTTGGAT
GAAGCCACGTCAGCTCTGGATACAGAAAGTGAAAAGGTTGTCCAAGAAGCCCTGGACAAA
GCCAGAGAAGGCCGCACCTGCATTGTGATTGCTCACCGCCTGTCCACCATCCAGAATGCA
GACTTAATAGTGGTGTTTCAGAATGGCAGAGTCAAGGAGCATGGCACGCATCAGCAGCTG
CTGGCACAGAAAGGCATCTATTTTTCAATGGTCAGTGTCCAGGCTGGAACAAAGCGCCAG
TGA

1. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8. [PubMed ]
2. Decleves X, Chevillard S, Charpentier C, Vielh P, Laplanche JL: A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein. Hum Mutat. 2000 May;15(5):486. [PubMed ]
3. Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, Schaeffeler E, Eichelbaum M, Brinkmann U, Roots I: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther. 2001 Mar;69(3):169-74. [PubMed ]
4. Kerb R, Hoffmeyer S, Brinkmann U: ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics. 2001 Feb;2(1):51-64. [PubMed ]
5. Saito S, Iida A, Sekine A, Miura Y, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y: Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population. J Hum Genet. 2002;47(1):38-50. [PubMed ]
6. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed ]
7. Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB: Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990 Jan 5;265(1):506-14. [PubMed ]
8. Gekeler V, Weger S, Probst H: mdr1/P-glycoprotein gene segments analyzed from various human leukemic cell lines exhibiting different multidrug resistance profiles. Biochem Biophys Res Commun. 1990 Jun 15;169(2):796-802. [PubMed ]
9. Kioka N, Tsubota J, Kakehi Y, Komano T, Gottesman MM, Pastan I, Ueda K: P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance. Biochem Biophys Res Commun. 1989 Jul 14;162(1):224-31. [PubMed ]
10. Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381-9. [PubMed ]
11. 2897240 Choi KH, Chen CJ, Kriegler M, Roninson IB: An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell. 1988 May 20;53(4):519-29.
12. 9038218 Chen G, Duran GE, Steger KA, Lacayo NJ, Jaffrezou JP, Dumontet C, Sikic BI: Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins. J Biol Chem. 1997 Feb 28;272(9):5974-82.
13. 9473242 Mickley LA, Lee JS, Weng Z, Zhan Z, Alvarez M, Wilson W, Bates SE, Fojo T: Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood. 1998 Mar 1;91(5):1749-56.

1. Jonsson O, Behnam-Motlagh P, Persson M, Henriksson R, Grankvist K: Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. Biochem Pharmacol. 1999 Dec 1;58(11):1801-6. [PubMed ]
2. Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, Spahn-Langguth H: Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. Int J Clin Pharmacol Ther. 2000 Apr;38(4):168-79. [PubMed ]
3. Hokama N, Hobara N, Sakai M, Kameya H, Ohshiro S, Sakanashi M: Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats. J Pharm Pharmacol. 2002 Jun;54(6):821-5. [PubMed ]
4. Kakumoto M, Sakaeda T, Takara K, Nakamura T, Kita T, Yagami T, Kobayashi H, Okamura N, Okumura K: Effects of carvedilol on MDR1-mediated multidrug resistance: comparison with verapamil. Cancer Sci. 2003 Jan;94(1):81-6. [PubMed ]
5. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed ]

1. Connexin-43
2. Cx43
3. Gap junction 43 kDa heart protein

MGDWSALGKLLDKVQAYSTAGGKVWLSVLFIFRILLLGTAVESAWGDEQSAFRCNTQQPG
CENVCYDKSFPISHVRFWVLQIIFVSVPTLLYLAHVFYVMRKEEKLNKKEEELKVAQTDG
VNVDMHLKQIEIKKFKYGIEEHGKVKMRGGLLRTYIISILFKSIFEVAFLLIQWYIYGFS
LSAVYTCKRDPCPHQVDCFLSRPTEKTIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRV
KGKSDPYHATSGALSPAKDCGSQKYAYFNGCSSPTAPLSPMSPPGYKLVTGDRNNSSCRN
YNKQASEQNWANYSAEQNRMGQAGSTISNSHAQPFDFPDDNQNSKKLAAGHELQPLAIVD
QRPSSRASSRASSRPRPDDLEI

• Connexin (PF00029 )
• Connexin43 (PF03508 )

• None

• 14-36
• 77-99
• 155-177
• 209-231

• Membrane
• multi-pass membrane protein

ATGGGTGACTGGAGCGCCTTAGGCAAACTCCTTGACAAGGTTCAAGCCTACTCAACTGCT
GGAGGGAAGGTGTGGCTGTCAGTACTTTTCATTTTCCGAATCCTGCTGCTGGGGACAGCG
GTTGAGTCAGCCTGGGGAGATGAGCAGTCTGCCTTTCGTTGTAACACTCAGCAACCTGGT
TGTGAAAATGTCTGCTATGACAAGTCTTTCCCAATCTCTCATGTGCGCTTCTGGGTCCTG
CAGATCATATTTGTGTCTGTACCCACACTCTTGTACCTGGCTCATGTGTTCTATGTGATG
CGAAAGGAAGAGAAACTGAACAAGAAAGAGGAAGAACTCAAGGTTGCCCAAACTGATGGT
GTCAATGTGGACATGCACTTGAAGCAGATTGAGATAAAGAAGTTCAAGTACGGTATTGAA
GAGCATGGTAAGGTGAAAATGCGAGGGGGGTTGCTGCGAACCTACATCATCAGTATCCTC
TTCAAGTCTATCTTTGAGGTGGCCTTCTTGCTGATCCAGTGGTACATCTATGGATTCAGC
TTGAGTGCTGTTTACACTTGCAAAAGAGATCCCTGCCCACATCAGGTGGACTGTTTCCTC
TCTCGCCCCACGGAGAAAACCATCTTCATCATCTTCATGCTGGTGGTGTCCTTGGTGTCC
CTGGCCTTGAATATCATTGAACTCTTCTATGTTTTCTTCAAGGGCGTTAAGGATCGGGTT
AAGGGAAAGAGCGACCCTTACCATGCGACCAGTGGTGCGCTGAGCCCTGCCAAAGACTGT
GGGTCTCAAAAATATGCTTATTTCAATGGCTGCTCCTCACCAACCGCTCCCCTCTCGCCT
ATGTCTCCTCCTGGGTACAAGCTGGTTACTGGCGACAGAAACAATTCTTCTTGCCGCAAT
TACAACAAGCAAGCAAGTGAGCAAAACTGGGCTAATTACAGTGCAGAACAAAATCGAATG
GGGCAGGCGGGAAGCACCATCTCTAACTCCCATGCACAGCCTTTTGATTTCCCCGATGAT
AACCAGAATTCTAAAAAACTAGCTGCTGGACATGAATTACAGCCACTAGCCATTGTGGAC
CAGCGACCTTCAAGCAGAGCCAGCAGTCGTGCCAGCAGCAGACCTCGGCCTGATGACCTG
GAGATCTAG

1. Saffitz JE, Laing JG, Yamada KA: Connexin expression and turnover : implications for cardiac excitability. Circ Res. 2000 Apr 14;86(7):723-8. [PubMed ]
2. Liu XZ, Xia XJ, Adams J, Chen ZY, Welch KO, Tekin M, Ouyang XM, Kristiansen A, Pandya A, Balkany T, Arnos KS, Nance WE: Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet. 2001 Dec 1;10(25):2945-51. [PubMed ]
3. Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, Innis JW, Dinulos MB, Christian C, Hannibal MC, Jabs EW: Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet. 2003 Feb;72(2):408-18. Epub 2002 Nov 27. [PubMed ]
4. Fishman GI, Eddy RL, Shows TB, Rosenthal L, Leinwand LA: The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures. Genomics. 1991 May;10(1):250-6. [PubMed ]
5. Fishman GI, Spray DC, Leinwand LA: Molecular characterization and functional expression of the human cardiac gap junction channel. J Cell Biol. 1990 Aug;111(2):589-98. [PubMed ]
6. Britz-Cunningham SH, Shah MM, Zuppan CW, Fletcher WH: Mutations of the Connexin43 gap-junction gene in patients with heart malformations and defects of laterality. N Engl J Med. 1995 May 18;332(20):1323-9. [PubMed ]
7. Gebbia M, Towbin JA, Casey B: Failure to detect connexin43 mutations in 38 cases of sporadic and familial heterotaxy. Circulation. 1996 Oct 15;94(8):1909-12. [PubMed ]
8. Penman Splitt M, Tsai MY, Burn J, Goodship JA: Absence of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy. Heart. 1997 Apr;77(4):369-70. [PubMed ]
9. Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M: Intercellular calcium signaling via gap junction in connexin-43-transfected cells. J Biol Chem. 1998 Jan 16;273(3):1519-28. [PubMed ]
10. Toth T, Hajdu J, Marton T, Nagy B, Papp Z: connexin43 gene mutations and heterotaxy. Circulation. 1998 Jan 6-13;97(1):117-8. [PubMed ]

1. Yeh HI, Lee PY, Su CH, Tian TY, Ko YS, Tsai CH: Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment. Am J Hypertens. 2006 Feb;19(2):129-35. [PubMed ]
2. Fan SY, Ke YN, Zeng YJ, Wang Y, Cheng WL, Yang JR: [Effects and the mechanism of carvedilol on gap junctional intercellular communication in rat myocardium] Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Dec;33(12):1141-5. [PubMed ]

1. CD106 antigen
2. INCAM-100
3. V-CAM 1
4. Vascular cell adhesion protein 1 precursor

MPGKMVVILGASNILWIMFAASQAFKIETTPESRYLAQIGDSVSLTCSTTGCESPFFSWR
TQIDSPLNGKVTNEGTTSTLTMNPVSFGNEHSYLCTATCESRKLEKGIQVEIYSFPKDPE
IHLSGPLEAGKPITVKCSVADVYPFDRLEIDLLKGDHLMKSQEFLEDADRKSLETKSLEV
TFTPVIEDIGKVLVCRAKLHIDEMDSVPTVRQAVKELQVYISPKNTVISVNPSTKLQEGG
SVTMTCSSEGLPAPEIFWSKKLDNGNLQHLSGNATLTLIAMRMEDSGIYVCEGVNLIGKN
RKEVELIVQEKPFTVEISPGPRIAAQIGDSVMLTCSVMGCESPSFSWRTQIDSPLSGKVR
SEGTNSTLTLSPVSFENEHSYLCTVTCGHKKLEKGIQVELYSFPRDPEIEMSGGLVNGSS
VTVSCKVPSVYPLDRLEIELLKGETILENIEFLEDTDMKSLENKSLEMTFIPTIEDTGKA
LVCQAKLHIDDMEFEPKQRQSTQTLYVNVAPRDTTVLVSPSSILEEGSSVNMTCLSQGFP
APKILWSRQLPNGELQPLSENATLTLISTKMEDSGVYLCEGINQAGRSRKEVELIIQVTP
KDIKLTAFPSESVKEGDTVIISCTCGNVPETWIILKKKAETGDTVLKSIDGAYTIRKAQL
KDAGVYECESKNKVGSQLRSLTLDVQGRENNKDYFSPELLVLYFASSLIIPAIGMIIYFA
RKANMKGSYSLVEAQKSKV

• ig (PF00047 )
• C2-set (PF05790 )
• I-set (PF07679 )
• V-set (PF07686 )

• 1-24

• 699-720

• Membrane
• single-pass type I membrane protein

ATGCCTGGGAAGATGGTCGTGATCCTTGGAGCCTCAAATATACTTTGGATAATGTTTGCA
GCTTCTCAAGCTTTTAAAATCGAGACCACCCCAGAATCTAGATATCTTGCTCAGATTGGT
GACTCCGTCTCATTGACTTGCAGCACCACAGGCTGTGAGTCCCCATTTTTCTCTTGGAGA
ACCCAGATAGATAGTCCACTGAATGGGAAGGTGACGAATGAGGGGACCACATCTACGCTG
ACAATGAATCCTGTTAGTTTTGGGAACGAACACTCTTACCTGTGCACAGCAACTTGTGAA
TCTAGGAAATTGGAAAAAGGAATCCAGGTGGAGATCTACTCTTTTCCTAAGGATCCAGAG
ATTCATTTGAGTGGCCCTCTGGAGGCTGGGAAGCCGATCACAGTCAAGTGTTCAGTTGCT
GATGTATACCCATTTGACAGGCTGGAGATAGACTTACTGAAAGGAGATCATCTCATGAAG
AGTCAGGAATTTCTGGAGGATGCAGACAGGAAGTCCCTGGAAACCAAGAGTTTGGAAGTA
ACCTTTACTCCTGTCATTGAGGATATTGGAAAAGTTCTTGTTTGCCGAGCTAAATTACAC
ATTGATGAAATGGATTCTGTGCCCACAGTAAGGCAGGCTGTAAAAGAATTGCAAGTCTAC
ATATCACCCAAGAATACAGTTATTTCTGTGAATCCATCCACAAAGCTGCAAGAAGGTGGC
TCTGTGACCATGACCTGTTCCAGCGAGGGTCTACCAGCTCCAGAGATTTTCTGGAGTAAG
AAATTAGATAATGGGAATCTACAGCACCTTTCTGGAAATGCAACTCTCACCTTAATTGCT
ATGAGGATGGAAGATTCTGGAATTTATGTGTGTGAAGGAGTTAATTTGATTGGGAAAAAC
AGAAAAGAGGTGGAATTAATTGTTCAAGAGAAACCATTTACTGTTGAGATCTCCCCTGGA
CCCCGGATTGCTGCTCAGATTGGAGACTCAGTCATGTTGACATGTAGTGTCATGGGCTGT
GAATCCCCATCTTTCTCCTGGAGAACCCAGATAGACAGCCCTCTGAGCGGGAAGGTGAGG
AGTGAGGGGACCAATTCCACGCTGACCCTGAGCCCTGTGAGTTTTGAGAACGAACACTCT
TATCTGTGCACAGTGACTTGTGGACATAAGAAACTGGAAAAGGGAATCCAGGTGGAGCTC
TACTCATTCCCTAGAGATCCAGAAATCGAGATGAGTGGTGGCCTCGTGAATGGGAGCTCT
GTCACTGTAAGCTGCAAGGTTCCTAGCGTGTACCCCCTTGACCGGCTGGAGATTGAATTA
CTTAAGGGGGAGACTATTCTGGAGAATATAGAGTTTTTGGAGGATACGGATATGAAATCT
CTAGAGAACAAAAGTTTGGAAATGACCTTCATCCCTACCATTGAAGATACTGGAAAAGCT
CTTGTTTGTCAGGCTAAGTTACATATTGATGACATGGAATTCGAACCCAAACAAAGGCAG
AGTACGCAAACACTTTATGTCAATGTTGCCCCCAGAGATACAACCGTCTTGGTCAGCCCT
TCCTCCATCCTGGAGGAAGGCAGTTCTGTGAATATGACATGCTTGAGCCAGGGCTTTCCT
GCTCCGAAAATCCTGTGGAGCAGGCAGCTCCCTAACGGGGAGCTACAGCCTCTTTCTGAG
AATGCAACTCTCACCTTAATTTCTACAAAAATGGAAGATTCTGGGGTTTATTTATGTGAA
GGAATTAACCAGGCTGGAAGAAGCAGAAAGGAAGTGGAATTAATTATCCAAGTTACTCCA
AAAGACATAAAACTTACAGCTTTTCCTTCTGAGAGTGTCAAAGAAGGAGACACTGTCATC
ATCTCTTGTACATGTGGAAATGTTCCAGAAACATGGATAATCCTGAAGAAAAAAGCGGAG
ACAGGAGACACAGTACTAAAATCTATAGATGGCGCCTATACCATCCGAAAGGCCCAGTTG
AAGGATGCGGGAGTATATGAATGTGAATCTAAAAACAAAGTTGGCTCACAATTAAGAAGT
TTAACACTTGATGTTCAAGGAAGAGAAAACAACAAAGACTATTTTTCTCCTGAGCTTCTC
GTGCTCTATTTTGCATCCTCCTTAATAATACCTGCCATTGGAATGATAATTTACTTTGCA
AGAAAAGCCAACATGAAGGGGTCATATAGTCTTGTAGAAGCACAGAAATCAAAAGTGTAG

1. Osborn L, Vassallo C, Benjamin CD: Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1. J Exp Med. 1992 Jul 1;176(1):99-107. [PubMed ]
2. Iademarco MF, McQuillan JJ, Rosen GD, Dean DC: Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem. 1992 Aug 15;267(23):16323-9. [PubMed ]
3. Polte T, Newman W, Gopal TV: Full length vascular cell adhesion molecule 1 (VCAM-1). Nucleic Acids Res. 1990 Oct 11;18(19):5901. [PubMed ]
4. Cybulsky MI, Fries JW, Williams AJ, Sultan P, Davis VM, Gimbrone MA Jr, Collins T: Alternative splicing of human VCAM-1 in activated vascular endothelium. Am J Pathol. 1991 Apr;138(4):815-20. [PubMed ]
5. Hession C, Tizard R, Vassallo C, Schiffer SB, Goff D, Moy P, Chi-Rosso G, Luhowskyj S, Lobb R, Osborn L: Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem. 1991 Apr 15;266(11):6682-5. [PubMed ]
6. Cybulsky MI, Fries JW, Williams AJ, Sultan P, Eddy R, Byers M, Shows T, Gimbrone MA Jr, Collins T: Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7859-63. [PubMed ]
7. Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R: Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203-11. [PubMed ]
8. Jones EY, Harlos K, Bottomley MJ, Robinson RC, Driscoll PC, Edwards RM, Clements JM, Dudgeon TJ, Stuart DI: Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution. Nature. 1995 Feb 9;373(6514):539-44. [PubMed ]
9. Wang JH, Pepinsky RB, Stehle T, Liu JH, Karpusas M, Browning B, Osborn L: The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5714-8. [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 ]