Showing drug card for Imatinib (DB00619)

• APRD01028

• Approved
• Small Molecule

1. Imatinib Mesylate
2. Imatinib Methansulfonate

1. Gleevec
2. Glivec

• Show PDF (issued on 2001-05-01)
• Show PDF (issued on 2003-04-01)

• Antineoplastic Agents
• Protein Kinase Inhibitors

• L01XE01

• 10:00.00
• 92:00.00

• Take with food to reduce the incidence of gastric irritation. Follow with a large glass of water. A lipid rich meal will slightly reduce and delay absorption. Avoid grapefruit and grapefruit juice throughout treatment, grapefruit can significantly increase serum levels of this product.

1. Vigneri P, Wang JY: Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med. 2001 Feb;7(2):228-34. [PubMed ]
2. Deininger MW, Druker BJ: Specific targeted therapy of chronic myelogenous leukemia with imatinib. Pharmacol Rev. 2003 Sep;55(3):401-23. Epub 2003 Jul 17. [PubMed ]
3. Lassila M, Allen TJ, Cao Z, Thallas V, Jandeleit-Dahm KA, Candido R, Cooper ME: Imatinib attenuates diabetes-associated atherosclerosis. Arterioscler Thromb Vasc Biol. 2004 May;24(5):935-42. Epub 2004 Feb 26. [PubMed ]
4. Reeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg MB, Veach D, Bornmann W, Sherman M, Kalman D: Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat Med. 2005 Jul;11(7):731-9. Epub 2005 Jun 26. [PubMed ]
5. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL: Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. [PubMed ]
6. Wikipedia
7. RxList

• Humans and other mammals

1. Cytochrome P450 3A4 (CYP3A4)

1. Proto-oncogene tyrosine-protein kinase ABL1
2. Beta platelet-derived growth factor receptor
3. Mast/stem cell growth factor receptor
4. Alpha platelet-derived growth factor receptor
5. Macrophage colony-stimulating factor 1 receptor
6. Multidrug resistance protein 1
7. High affinity nerve growth factor receptor
8. ATP-binding cassette sub-family G member 2
9. RET proto-oncogene
10. Epithelial discoidin domain-containing receptor 1

ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA

1. Abelson murine leukemia viral oncogene homolog 1
2. EC 2.7.10.2
3. c- ABL
4. p150

MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSE
NDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVN
SLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTAS
DGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERT
DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ
LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFI
HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKS
DVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP
SDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAE
HRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLF
SALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSP
KPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSAS
CVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTV
TPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGS
ALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPP
PPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVL
PATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPE
RIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNK
FAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• SH2 (PF00017 )
• SH3_1 (PF00018 )
• Pkinase_Tyr (PF07714 )

• None

• None

• Cytoplasm

ATGTTGGAGATCTGCCTGAAGCTGGTGGGCTGCAAATCCAAGAAGGGGCTGTCCTCGTCC
TCCAGCTGTTATCTGGAAGAAGCCCTTCAGCGGCCAGTAGCATCTGACTTTGAGCCTCAG
GGTCTGAGTGAAGCCGCTCGTTGGAACTCCAAGGAAAACCTTCTCGCTGGACCCAGTGAA
AATGACCCCAACCTTTTCGTTGCACTGTATGATTTTGTGGCCAGTGGAGATAACACTCTA
AGCATAACTAAAGGTGAAAAGCTCCGGGTCTTAGGCTATAATCACAATGGGGAATGGTGT
GAAGCCCAAACCAAAAATGGCCAAGGCTGGGTCCCAAGCAACTACATCACGCCAGTCAAC
AGTCTGGAGAAACACTCCTGGTACCATGGGCCTGTGTCCCGCAATGCCGCTGAGTATCTG
CTGAGCAGCGGGATCAATGGCAGCTTCTTGGTGCGTGAGAGTGAGAGCAGTCCTGGCCAG
AGGTCCATCTCGCTGAGATACGAAGGGAGGGTGTACCATTACAGGATCAACACTGCTTCT
GATGGCAAGCTCTACGTCTCCTCCGAGAGCCGCTTCAACACCCTGGCCGAGTTGGTTCAT
CATCATTCAACGGTGGCCGACGGGCTCATCACCACGCTCCATTATCCAGCCCCAAAGCGC
AACAAGCCCACTGTCTATGGTGTGTCCCCCAACTACGACAAGTGGGAGATGGAACGCACG
GACATCACCATGAAGCACAAGCTGGGCGGGGGCCAGTACGGGGAGGTGTACGAGGGCGTG
TGGAAGAAATACAGCCTGACGGTGGCCGTGAAGACCTTGAAGGAGGACACCATGGAGGTG
GAAGAGTTCTTGAAAGAAGCTGCAGTCATGAAAGAGATCAAACACCCTAACCTGGTGCAG
CTCCTTGGGGTCTGCACCCGGGAGCCCCCGTTCTATATCATCACTGAGTTCATGACCTAC
GGGAACCTCCTGGACTACCTGAGGGAGTGCAACCGGCAGGAGGTGAACGCCGTGGTGCTG
CTGTACATGGCCACTCAGATCTCGTCAGCCATGGAGTACCTGGAGAAGAAAAACTTCATC
CACAGAGATCTTGCTGCCCGAAACTGCCTGGTAGGGGAGAACCACTTGGTGAAGGTAGCT
GATTTTGGCCTGAGCAGGTTGATGACAGGGGACACCTACACAGCCCATGCTGGAGCCAAG
TTCCCCATCAAATGGACTGCACCCGAGAGCCTGGCCTACAACAAGTTCTCCATCAAGTCC
GACGTCTGGGCATTTGGAGTATTGCTTTGGGAAATTGCTACCTATGGCATGTCCCCTTAC
CCGGGAATTGACCTGTCCCAGGTGTATGAGCTGCTAGAGAAGGACTACCGCATGGAGCGC
CCAGAAGGCTGCCCAGAGAAGGTCTATGAACTCATGCGAGCATGTTGGCAGTGGAATCCC
TCTGACCGGCCCTCCTTTGCTGAAATCCACCAAGCCTTTGAAACAATGTTCCAGGAATCC
AGTATCTCAGACGAAGTGGAAAAGGAGCTGGGGAAACAAGGCGTCCGTGGGGCTGTGAGT
ACCTTGCTGCAGGCCCCAGAGCTGCCCACCAAGACGAGGACCTCCAGGAGAGCTGCAGAG
CACAGAGACACCACTGACGTGCCTGAGATGCCTCACTCCAAGGGCCAGGGAGAGAGCGAT
CCTCTGGACCATGAGCCTGCCGTGTCTCCATTGCTCCCTCGAAAAGAGCGAGGTCCCCCG
GAGGGCGGCCTGAATGAAGATGAGCGCCTTCTCCCCAAAGACAAAAAGACCAACTTGTTC
AGCGCCTTGATCAAGAAGAAGAAGAAGACAGCCCCAACCCCTCCCAAACGCAGCAGCTCC
TTCCGGGAGATGGACGGCCAGCCGGAGCGCAGAGGGGCCGGCGAGGAAGAGGGCCGAGAC
ATCAGCAACGGGGCACTGGCTTTCACCCCCTTGGACACAGCTGACCCAGCCAAGTCCCCA
AAGCCCAGCAATGGGGCTGGGGTCCCCAATGGAGCCCTCCGGGAGTCCGGGGGCTCAGGC
TTCCGGTCTCCCCACCTGTGGAAGAAGTCCAGCACGCTGACCAGCAGCCGCCTAGCCACC
GGCGAGGAGGAGGGCGGTGGCAGCTCCAGCAAGCGCTTCCTGCGCTCTTGCTCCGCCTCC
TGCGTTCCCCATGGGGCCAAGGACACGGAGTGGAGGTCAGTCACGCTGCCTCGGGACTTG
CAGTCCACGGGAAGACAGTTTGACTCGTCCACATTTGGAGGGCACAAAAGTGAGAAGCCG
GCTCTGCCTCGGAAGAGGGCAGGGGAGAACAGGTCTGACCAGGTGACCCGAGGCACAGTA
ACGCCTCCCCCCAGGCTGGTGAAAAAGAATGAGGAAGCTGCTGATGAGGTCTTCAAAGAC
ATCATGGAGTCCAGCCCGGGCTCCAGCCCGCCCAACCTGACTCCAAAACCCCTCCGGCGG
CAGGTCACCGTGGCCCCTGCCTCGGGCCTCCCCCACAAGGAAGAAGCTGAAAAGGGCAGT
GCCTTAGGGACCCCTGCTGCAGCTGAGCCAGTGACCCCCACCAGCAAAGCAGGCTCAGGT
GCACCAGGGGGCACCAGCAAGGGCCCCGCCGAGGAGTCCAGAGTGAGGAGGCACAAGCAC
TCCTCTGAGTCGCCAGGGAGGGACAAGGGGAAATTGTCCAGGCTCAAACCTGCCCCGCCG
CCCCCACCAGCAGCCTCTGCAGGGAAGGCTGGAGGAAAGCCCTCGCAGAGCCCGAGCCAG
GAGGCGGCCGGGGAGGCAGTCCTGGGCGCAAAGACAAAAGCCACGAGTCTGGTTGATGCT
GTGAACAGTGACGCTGCCAAGCCCAGCCAGCCGGGAGAGGGCCTCAAAAAGCCCGTGCTC
CCGGCCACTCCAAAGCCACAGTCCGCCAAGCCGTCGGGGACCCCCATCAGCCCAGCCCCC
GTTCCCTCCACGTTGCCATCAGCATCCTCGGCCCTGGCAGGGGACCAGCCGTCTTCCACT
GCCTTCATCCCTCTCATATCAACCCGAGTGTCTCTTCGGAAAACCCGCCAGCCTCCAGAG
CGGATCGCCAGCGGCGCCATCACCAAGGGCGTGGTCCTGGACAGCACCGAGGCGCTGTGC
CTCGCCATCTCTAGGAACTCCGAGCAGATGGCCAGCCACAGCGCAGTGCTGGAGGCCGGC
AAAAACCTCTACACGTTCTGCGTGAGCTATGTGGATTCCATCCAGCAAATGAGGAACAAG
TTTGCCTTCCGAGAGGCCATCAACAAACTGGAGAATAATCTCCGGGAGCTTCAGATCTGC
CCGGCGACAGCAGGCAGTGGTCCGGCGGCCACTCAGGACTTCAGCAAGCTCCTCAGTTCG
GTGAAGGAAATCAGTGACATAGTGCAGAGGTAG

1. Lin WH, Huang CJ, Liu MW, Chang HM, Chen YJ, Tai TY, Chuang LM: Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B. Genomics. 2001 May 15;74(1):12-20. [PubMed ]
2. Donaldson LW, Gish G, Pawson T, Kay LE, Forman-Kay JD: Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14053-8. Epub 2002 Oct 16. [PubMed ]
3. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC: Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):443-8. Epub 2003 Jan 9. [PubMed ]
4. Overduin M, Mayer B, Rios CB, Baltimore D, Cowburn D: Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11673-7. [PubMed ]
5. Overduin M, Rios CB, Mayer BJ, Baltimore D, Cowburn D: Three-dimensional solution structure of the src homology 2 domain of c-abl. Cell. 1992 Aug 21;70(4):697-704. [PubMed ]
6. Fainstein E, Einat M, Gokkel E, Marcelle C, Croce CM, Gale RP, Canaani E: Nucleotide sequence analysis of human abl and bcr-abl cDNAs. Oncogene. 1989 Dec;4(12):1477-81. [PubMed ]
7. Fainstein E, Marcelle C, Rosner A, Canaani E, Gale RP, Dreazen O, Smith SD, Croce CM: A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia. Nature. 1987 Nov 26-Dec 2;330(6146):386-8. [PubMed ]
8. Shtivelman E, Lifshitz B, Gale RP, Roe BA, Canaani E: Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene. Cell. 1986 Oct 24;47(2):277-84. [PubMed ]
9. Groffen J, Heisterkamp N, Reynolds FH Jr, Stephenson JR: Homology between phosphotyrosine acceptor site of human c-abl and viral oncogene products. Nature. 1983 Jul 14-20;304(5922):167-9. [PubMed ]
10. Inokuchi K, Futaki M, Dan K, Nomura T: Sequence analysis of the mutation at codon 834 and the sequence variation of codon 837 of c-abl gene. Leukemia. 1994 Feb;8(2):343-4. [PubMed ]
11. 7665185 Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton SW, Crabtree J, Freeman A, Iyer K, Jian L, et al.: Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics. 1995 May 1;27(1):67-82.
12. 7892170 Pisabarro MT, Ortiz AR, Serrano L, Wade RC: Homology modeling of the Abl-SH3 domain. Proteins. 1994 Nov;20(3):203-15.
13. 8590002 Gosser YQ, Zheng J, Overduin M, Mayer BJ, Cowburn D: The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct. Structure. 1995 Oct 15;3(10):1075-86.
14. 8805596 Nam HJ, Haser WG, Roberts TM, Frederick CA: Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism. Structure. 1996 Sep 15;4(9):1105-14.
15. 9168116 Baskaran R, Wood LD, Whitaker LL, Canman CE, Morgan SE, Xu Y, Barlow C, Baltimore D, Wynshaw-Boris A, Kastan MB, Wang JY: Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature. 1997 May 29;387(6632):516-9.
16. 9698566 Pisabarro MT, Serrano L, Wilmanns M: Crystal structure of the abl-SH3 domain complexed with a designed high-affinity peptide ligand: implications for SH3-ligand interactions. J Mol Biol. 1998 Aug 21;281(3):513-21.

1. Hoerth E, Kodym R: Involvment of c-Abl in the radiation-induced inhibition of myoblast differentiation. Int J Radiat Biol. 2004 Oct;80(10):729-36. [PubMed ]
2. Dewar AL, Zannettino AC, Hughes TP, Lyons AB: Inhibition of c-fms by imatinib: expanding the spectrum of treatment. Cell Cycle. 2005 Jul;4(7):851-3. Epub 2005 Jul 28. [PubMed ]
3. Agirre X, Roman-Gomez J, Vazquez I, Jimenez-Velasco A, Larrayoz MJ, Lahortiga I, Andreu EJ, Marquez J, Beltran de Heredia JM, Odero MD, Prosper F, Calasanz MJ: Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib. Cancer Genet Cytogenet. 2005 Jul 1;160(1):22-6. [PubMed ]
4. Brueggemeier SB, Wu D, Kron SJ, Palecek SP: Protein-acrylamide copolymer hydrogels for array-based detection of tyrosine kinase activity from cell lysates. Biomacromolecules. 2005 Sep-Oct;6(5):2765-75. [PubMed ]
5. Haberler C, Gelpi E, Marosi C, Rossler K, Birner P, Budka H, Hainfellner JA: Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol. 2006 Jan;76(2):105-9. [PubMed ]

1. Beta platelet-derived growth factor receptor precursor
2. CD140b antigen
3. EC 2.7.10.1
4. PDGF-R-beta

MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPV
VWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFV
PDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFS
GIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGN
EVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDH
QDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDS
SAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVL
ELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNV
TYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILA
LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQL
VLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGP
HLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNAL
PVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVP
SAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLV
KICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLG
GTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLER
LLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDND
YIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQV
EPEPELEQLPDSGCPAPRAEAEDSFL

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• ig (PF00047 )
• Pkinase_Tyr (PF07714 )

• 1-32

• 532-556

• Membrane
• single-pass type I membrane protein

ATGCGGCTTCCGGGTGCGATGCCAGCTCTGGCCCTCAAAGGCGAGCTGCTGTTGCTGTCT
CTCCTGTTACTTCTGGAACCACAGATCTCTCAGGGCCTGGTCGTCACACCCCCGGGGCCA
GAGCTTGTCCTCAATGTCTCCAGCACCTTCGTTCTGACCTGCTCGGGTTCAGCTCCGGTG
GTGTGGGAACGGATGTCCCAGGAGCCCCCACAGGAAATGGCCAAGGCCCAGGATGGCACC
TTCTCCAGCGTGCTCACACTGACCAACCTCACTGGGCTAGACACGGGAGAATACTTTTGC
ACCCACAATGACTCCCGTGGACTGGAGACCGATGAGCGGAAACGGCTCTACATCTTTGTG
CCAGATCCCACCGTGGGCTTCCTCCCTAATGATGCCGAGGAACTATTCATCTTTCTCACG
GAAATAACTGAGATCACCATTCCATGCCGAGTAACAGACCCACAGCTGGTGGTGACACTG
CACGAGAAGAAAGGGGACGTTGCACTGCCTGTCCCCTATGATCACCAACGTGGCTTTTCT
GGTATCTTTGAGGACAGAAGCTACATCTGCAAAACCACCATTGGGGACAGGGAGGTGGAT
TCTGATGCCTACTATGTCTACAGACTCCAGGTGTCATCCATCAACGTCTCTGTGAACGCA
GTGCAGACTGTGGTCCGCCAGGGTGAGAACATCACCCTCATGTGCATTGTGATCGGGAAT
GAGGTGGTCAACTTCGAGTGGACATACCCCCGCAAAGAAAGTGGGCGGCTGGTGGAGCCG
GTGACTGACTTCCTCTTGGATATGCCTTACCACATCCGCTCCATCCTGCACATCCCCAGT
GCCGAGTTAGAAGACTCGGGGACCTACACCTGCAATGTGACGGAGAGTGTGAATGACCAT
CAGGATGAAAAGGCCATCAACATCACCGTGGTTGAGAGCGGCTACGTGCGGCTCCTGGGA
GAGGTGGGCACACTACAATTTGCTGAGCTGCATCGGAGCCGGACACTGCAGGTAGTGTTC
GAGGCCTACCCACCGCCCACTGTCCTGTGGTTCAAAGACAACCGCACCCTGGGCGACTCC
AGCGCTGGCGAAATCGCCCTGTCCACGCGCAACGTGTCGGAGACCCGGTATGTGTCAGAG
CTGACACTGGTTCGCGTGAAGGTGGCAGAGGCTGGCCACTACACCATGCGGGCCTTCCAT
GAGGATGCTGAGGTCCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTGCTG
GAGCTAAGTGAGAGCCACCCTGACAGTGGGGAACAGACAGTCCGCTGTCGTGGCCGGGGC
ATGCCCCAGCCGAACATCATCTGGTCTGCCTGCAGAGACCTCAAAAGGTGTCCACGTGAG
CTGCCGCCCACGCTGCTGGGGAACAGTTCCGAAGAGGAGAGCCAGCTGGAGACTAACGTG
ACGTACTGGGAGGAGGAGCAGGAGTTTGAGGTGGTGAGCACACTGCGTCTGCAGCACGTG
GATCGGCCACTGTCGGTGCGCTGCACGCTGCGCAACGCTGTGGGCCAGGACACGCAGGAG
GTCATCGTGGTGCCACACTCCTTGCCCTTTAAGGTGGTGGTGATCTCAGCCATCCTGGCC
CTGGTGGTGCTCACCATCATCTCCCTTATCATCCTCATCATGCTTTGGCAGAAGAAGCCA
CGTTACGAGATCCGATGGAAGGTGATTGAGTCTGTGAGCTCTGACGGCCATGAGTACATC
TACGTGGACCCCATGCAGCTGCCCTATGACTCCACGTGGGAGCTGCCGCGGGACCAGCTT
GTGCTGGGACGCACCCTCGGCTCTGGGGCCTTTGGGCAGGTGGTGGAGGCCACGGCTCAT
GGCCTGAGCCATTCTCAGGCCACGATGAAAGTGGCCGTCAAGATGCTTAAATCCACAGCC
CGCAGCAGTGAGAAGCAAGCCCTTATGTCGGAGCTGAAGATCATGAGTCACCTTGGGCCC
CACCTGAACGTGGTCAACCTGTTGGGGGCCTGCACCAAAGGAGGACCCATCTATATCATC
ACTGAGTACTGCCGCTACGGAGACCTGGTGGACTACCTGCACCGCAACAAACACACCTTC
CTGCAGCACCACTCCGACAAGCGCCGCCCGCCCAGCGCGGAGCTCTACAGCAATGCTCTG
CCCGTTGGGCTCCCCCTGCCCAGCCATGTGTCCTTGACCGGGGAGAGCGACGGTGGCTAC
ATGGACATGAGCAAGGACGAGTCGGTGGACTATGTGCCCATGCTGGACATGAAAGGAGAC
GTCAAATATGCAGACATCGAGTCCTCCAACTACATGGCCCCTTACGATAACTACGTTCCC
TCTGCCCCTGAGAGGACCTGCCGAGCAACTTTGATCAACGAGTCTCCAGTGCTAAGCTAC
ATGGACCTCGTGGGCTTCAGCTACCAGGTGGCCAATGGCATGGAGTTTCTGGCCTCCAAG
AACTGCGTCCACAGAGACCTGGCGGCTAGGAACGTGCTCATCTGTGAAGGCAAGCTGGTC
AAGATCTGTGACTTTGGCCTGGCTCGAGACATCATGCGGGACTCGAATTACATCTCCAAA
GGCAGCACCTTTTTGCCTTTAAAGTGGATGGCTCCGGAGAGCATCTTCAACAGCCTCTAC
ACCACCCTGAGCGACGTGTGGTCCTTCGGGATCCTGCTCTGGGAGATCTTCACCTTGGGT
GGCACCCCTTACCCAGAGCTGCCCATGAACGAGCAGTTCTACAATGCCATCAAACGGGGT
TACCGCATGGCCCAGCCTGCCCATGCCTCCGACGAGATCTATGAGATCATGCAGAAGTGC
TGGGAAGAGAAGTTTGAGATTCGGCCCCCCTTCTCCCAGCTGGTGCTGCTTCTCGAGAGA
CTGTTGGGCGAAGGTTACAAAAAGAAGTACCAGCAGGTGGATGAGGAGTTTCTGAGGAGT
GACCACCCAGCCATCCTTCGGTCCCAGGCCCGCTTGCCTGGGTTCCATGGCCTCCGATCT
CCCCTGGACACCAGCTCCGTCCTCTATACTGCCGTGCAGCCCAATGAGGGTGACAACGAC
TATATCATCCCCCTGCCTGACCCCAAACCCGAGGTTGCTGACGAGGGCCCACTGGAGGGT
TCCCCCAGCCTAGCCAGCTCCACCCTGAATGAAGTCAACACCTCCTCAACCATCTCCTGT
GACAGCCCCCTGGAGCCCCAGGACGAACCAGAGCCAGAGCCCCAGCTTGAGCTCCAGGTG
GAGCCGGAGCCAGAGCTGGAACAGTTGCCGGATTCGGGGTGCCCTGCGCCTCGGGCGGAA
GCAGAGGATAGCTTCCTGTAG

1. Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U: PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol. 2001 May;3(5):512-6. [PubMed ]
2. Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN: NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1397-404. Epub 2001 Sep 21. [PubMed ]
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4. Kazlauskas A, Cooper JA: Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell. 1989 Sep 22;58(6):1121-33. [PubMed ]
5. Gronwald RG, Grant FJ, Haldeman BA, Hart CE, O'Hara PJ, Hagen FS, Ross R, Bowen-Pope DF, Murray MJ: Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class. Proc Natl Acad Sci U S A. 1988 May;85(10):3435-9. [PubMed ]
6. Roberts WM, Look AT, Roussel MF, Sherr CJ: Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. Cell. 1988 Nov 18;55(4):655-61. [PubMed ]
7. Claesson-Welsh L, Eriksson A, Moren A, Severinsson L, Ek B, Ostman A, Betsholtz C, Heldin CH: cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules. Mol Cell Biol. 1988 Aug;8(8):3476-86. [PubMed ]
8. Welsh M, Mares J, Karlsson T, Lavergne C, Breant B, Claesson-Welsh L: Shb is a ubiquitously expressed Src homology 2 protein. Oncogene. 1994 Jan;9(1):19-27. [PubMed ]
9. Chi KD, McPhee RA, Wagner AS, Dietz JJ, Pantazis P, Goustin AS: Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity. Oncogene. 1997 Aug 28;15(9):1051-7. [PubMed ]
10. Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito H: Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Blood. 1997 Dec 1;90(11):4271-7. [PubMed ]
11. 9989826 Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A: APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis. Oncogene. 1999 Jan 21;18(3):759-67.

1. Basciani S, Brama M, Mariani S, De Luca G, Arizzi M, Vesci L, Pisano C, Dolci S, Spera G, Gnessi L: Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Res. 2005 Mar 1;65(5):1897-903. [PubMed ]
2. Jones RL, Judson IR: The development and application of imatinib. Expert Opin Drug Saf. 2005 Mar;4(2):183-91. [PubMed ]
3. Modi S, Seidman AD, Dickler M, Moasser M, D'Andrea G, Moynahan ME, Menell J, Panageas KS, Tan LK, Norton L, Hudis CA: A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancer. Breast Cancer Res Treat. 2005 Mar;90(2):157-63. [PubMed ]
4. Johnson FM, Saigal B, Donato NJ: Induction of heparin-binding EGF-like growth factor and activation of EGF receptor in imatinib mesylate-treated squamous carcinoma cells. J Cell Physiol. 2005 Nov;205(2):218-27. [PubMed ]
5. Chen J, Rocken C, Nitsche B, Hosius C, Gschaidmeier H, Kahl S, Malfertheiner P, Ebert MP: The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression. Cancer Lett. 2006 Feb 28;233(2):328-37. [PubMed ]

1. CD117 antigen
2. EC 2.7.10.1
3. Mast/stem cell growth factor receptor precursor
4. Proto-oncogene tyrosine-protein kinase Kit
5. SCFR
6. c-kit

MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD
PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV
DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH
RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS
SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN
VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE
DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR
LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS
SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV
MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF
GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC
TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE
YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM
AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES
IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY
DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV
GSTASSSQPLLVHDDV

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• ig (PF00047 )
• Pkinase_Tyr (PF07714 )

• 1-25

• 525-545

• Membrane
• single-pass type I membrane protein

ATGAGAGGCGCTCGCGGCGCCTGGGATTTTCTCTGCGTTCTGCTCCTACTGCTTCGCGTC
CAGACAGGCTCTTCTCAACCATCTGTGAGTCCAGGGGAACCGTCTCCACCATCCATCCAT
CCAGGAAAATCAGACTTAATAGTCCGCGTGGGCGACGAGATTAGGCTGTTATGCACTGAT
CCGGGCTTTGTCAAATGGACTTTTGAGATCCTGGATGAAACGAATGAGAATAAGCAGAAT
GAATGGATCACGGAAAAGGCAGAAGCCACCAACACCGGCAAATACACGTGCACCAACAAA
CACGGCTTAAGCAATTCCATTTATGTGTTTGTTAGAGATCCTGCCAAGCTTTTCCTTGTT
GACCGCTCCTTGTATGGGAAAGAAGACAACGACACGCTGGTCCGCTGTCCTCTCACAGAC
CCAGAAGTGACCAATTATTCCCTCAAGGGGTGCCAGGGGAAGCCTCTTCCCAAGGACTTG
AGGTTTATTCCTGACCCCAAGGCGGGCATCATGATCAAAAGTGTGAAACGCGCCTACCAT
CGGCTCTGTCTGCATTGTTCTGTGGACCAGGAGGGCAAGTCAGTGCTGTCGGAAAAATTC
ATCCTGAAAGTGAGGCCAGCCTTCAAAGCTGTGCCTGTTGTGTCTGTGTCCAAAGCAAGC
TATCTTCTTAGGGAAGGGGAAGAATTCACAGTGACGTGCACAATAAAAGATGTGTCTAGT
TCTGTGTACTCAACGTGGAAAAGAGAAAACAGTCAGACTAAACTACAGGAGAAATATAAT
AGCTGGCATCACGGTGACTTCAATTATGAACGTCAGGCAACGTTGACTATCAGTTCAGCG
AGAGTTAATGATTCTGGAGTGTTCATGTGTTATGCCAATAATACTTTTGGATCAGCAAAT
GTCACAACAACCTTGGAAGTAGTAGATAAAGGATTCATTAATATCTTCCCCATGATAAAC
ACTACAGTATTTGTAAACGATGGAGAAAATGTAGATTTGATTGTTGAATATGAAGCATTC
CCCAAACCTGAACACCAGCAGTGGATCTATATGAACAGAACCTTCACTGATAAATGGGAA
GATTATCCCAAGTCTGAGAATGAAAGTAATATCAGATACGTAAGTGAACTTCATCTAACG
AGATTAAAAGGCACCGAAGGAGGCACTTACACATTCCTAGTGTCCAATTCTGACGTCAAT
GCTGCCATAGCATTTAATGTTTATGTGAATACAAAACCAGAAATCCTGACTTACGACAGG
CTCGTGAATGGCATGCTCCAATGTGTGGCAGCAGGATTCCCAGAGCCCACAATAGATTGG
TATTTTTGTCCAGGAACTGAGCAGAGATGCTCTGCTTCTGTACTGCCAGTGGATGTGCAG
ACACTAAACTCATCTGGGCCACCGTTTGGAAAGCTAGTGGTTCAGAGTTCTATAGATTCT
AGTGCATTCAAGCACAATGGCACGGTTGAATGTAAGGCTTACAACGATGTGGGCAAGACT
TCTGCCTATTTTAACTTTGCATTTAAAGGTAACAACAAAGAGCAAATCCATCCCCACACC
CTGTTCACTCCTTTGCTGATTGGTTTCGTAATCGTAGCTGGCATGATGTGCATTATTGTG
ATGATTCTGACCTACAAATATTTACAGAAACCCATGTATGAAGTACAGTGGAAGGTTGTT
GAGGAGATAAATGGAAACAATTATGTTTACATAGACCCAACACAACTTCCTTATGATCAC
AAATGGGAGTTTCCCAGAAACAGGCTGAGTTTTGGGAAAACCCTGGGTGCTGGAGCTTTC
GGGAAGGTTGTTGAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGACTGTC
GCTGTAAAGATGCTCAAGCCGAGTGCCCATTTGACAGAACGGGAAGCCCTCATGTCTGAA
CTCAAAGTCCTGAGTTACCTTGGTAATCACATGAATATTGTGAATCTACTTGGAGCCTGC
ACCATTGGAGGGCCCACCCTGGTCATTACAGAATATTGTTGCTATGGTGATCTTTTGAAT
TTTTTGAGAAGAAAACGTGATTCATTTATTTGTTCAAAGCAGGAAGATCATGCAGAAGCT
GCACTTTATAAGAATCTTCTGCATTCAAAGGAGTCTTCCTGCAGCGATAGTACTAATGAG
TACATGGACATGAAACCTGGAGTTTCTTATGTTGTCCCAACCAAGGCCGACAAAAGGAGA
TCTGTGAGAATAGGCTCATACATAGAAAGAGATGTGACTCCCGCCATCATGGAGGATGAC
GAGTTGGCCCTAGACTTAGAAGACTTGCTGAGCTTTTCTTACCAGGTGGCAAAGGGCATG
GCTTTCCTCGCCTCCAAGAATTGTATTCACAGAGACTTGGCAGCCAGAAATATCCTCCTT
ACTCATGGTCGGATCACAAAGATTTGTGATTTTGGTCTAGCCAGAGACATCAAGAATGAT
TCTAATTATGTGGTTAAAGGAAACGCTCGACTACCTGTGAAGTGGATGGCACCTGAAAGC
ATTTTCAACTGTGTATACACGTTTGAAAGTGACGTCTGGTCCTATGGGATTTTTCTTTGG
GAGCTGTTCTCTTTAGGAAGCAGCCCCTATCCTGGAATGCCGGTCGATTCTAAGTTCTAC
AAGATGATCAAGGAAGGCTTCCGGATGCTCAGCCCTGAACACGCACCTGCTGAAATGTAT
GACATAATGAAGACTTGCTGGGATGCAGATCCCCTAAAAAGACCAACATTCAAGCAAATT
GTTCAGCTAATTGAGAAGCAGATTTCAGAGAGCACCAATCATATTTACTCCAACTTAGCA
AACTGCAGCCCCAACCGACAGAAGCCCGTGGTAGACCATTCTGTGCGGATCAATTCTGTC
GGCAGCACCGCTTCCTCCTCCCAGCCTCTGCTTGTGCACGACGATGTCTGA

1. Mancini A, Koch A, Stefan M, Niemann H, Tamura T: The direct association of the multiple PDZ domain containing proteins (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase activity. FEBS Lett. 2000 Sep 29;482(1-2):54-8. [PubMed ]
2. Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Ronnstrand L: The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit. Biochem J. 2003 Mar 15;370(Pt 3):1033-8. [PubMed ]
3. Giebel LB, Strunk KM, Holmes SA, Spritz RA: Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. Oncogene. 1992 Nov;7(11):2207-17. [PubMed ]
4. Spritz RA, Giebel LB, Holmes SA: Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am J Hum Genet. 1992 Feb;50(2):261-9. [PubMed ]
5. Fleischman RA: Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene. J Clin Invest. 1992 Jun;89(6):1713-7. [PubMed ]
6. Giebel LB, Spritz RA: Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8696-9. [PubMed ]
7. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A: Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341-51. [PubMed ]
8. Spritz RA, Holmes SA, Itin P, Kuster W: Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. J Invest Dermatol. 1993 Jul;101(1):22-5. [PubMed ]
9. Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, Kanayama Y, et al.: Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest. 1993 Oct;92(4):1736-44. [PubMed ]
10. Riva P, Milani N, Gandolfi P, Larizza L: A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian kindred with piebaldism. Hum Mutat. 1995;6(4):343-5. [PubMed ]
11. 9027509 Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F: Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. Genomics. 1997 Jan 15;39(2):216-26.
12. 9697690 Nishida T, Hirota S, Taniguchi M, Hashimoto K, Isozaki K, Nakamura H, Kanakura Y, Tanaka T, Takabayashi A, Matsuda H, Kitamura Y: Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet. 1998 Aug;19(4):323-4.

1. Dy GK, Miller AA, Mandrekar SJ, Aubry MC, Langdon RM Jr, Morton RF, Schild SE, Jett JR, Adjei AA: A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Ann Oncol. 2005 Nov;16(11):1811-6. Epub 2005 Aug 8. [PubMed ]
2. Lee JL, Kim JY, Ryu MH, Kang HJ, Chang HM, Kim TW, Lee H, Park JH, Kim HC, Kim JS, Kang YK: Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1. Dig Dis Sci. 2006 Jun;51(6):1043-6. [PubMed ]
3. De Giorgi U: KIT mutations and imatinib dose effects in patients with gastrointestinal stromal tumors. J Clin Oncol. 2007 Mar 20;25(9):1146-7; author reply 1147-8. [PubMed ]
4. Rutkowski P, Nowecki ZI, Debiec-Rychter M, Grzesiakowska U, Michej W, Wozniak A, Siedlecki JA, Limon J, Dobosz AJ, Kakol M, Osuch C, Ruka W: Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol. 2007 Sep;133(9):589-97. Epub 2007 Apr 26. [PubMed ]
5. Posadas EM, Kwitkowski V, Kotz HL, Espina V, Minasian L, Tchabo N, Premkumar A, Hussain MM, Chang R, Steinberg SM, Kohn EC: A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer. 2007 Jul 15;110(2):309-17. [PubMed ]

1. Alpha platelet-derived growth factor receptor precursor
2. CD140a antigen
3. EC 2.7.10.1
4. PDGF-R-alpha

MGTSHPAFLVLGCLLTGLSLILCQLSLPSILPNENEKVVQLNSSFSLRCFGESEVSWQYP
MSEEESSDVEIRNEENNSGLFVTVLEVSSASAAHTGLYTCYYNHTQTEENELEGRHIYIY
VPDPDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYDSRQGFNG
TFTVGPYICEATVKGKKFQTIPFNVYALKATSELDLEMEALKTVYKSGETIVVTCAVFNN
EVVDLQWTYPGEVKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVK
EMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEVRAYPPPRISWLKNNLTLIENL
TEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDL
VDDHHGSTGGQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRD
RSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAPTLRSELTVAAAVLVLLVIVII
SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLG
SGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNL
LGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSY
VILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKN
LLSDDNSEGLTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLA
RDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMM
VDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKK
SYEKIHLDFLKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYII
PLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTFIKREDETIEDIDMMDDIGIDS
SDLVEDSFL

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• ig (PF00047 )
• I-set (PF07679 )
• Pkinase_Tyr (PF07714 )

• 1-23

• 525-549

• Membrane
• single-pass type I membrane protein

ATGGGGACTTCCCATCCGGCGTTCCTGGTCTTAGGCTGTCTTCTCACAGGGCTGAGCCTA
ATCCTCTGCCAGCTTTCATTACCCTCTATCCTTCCAAATGAAAATGAAAAGGTTGTGCAG
CTGAATTCATCCTTTTCTCTGAGATGCTTTGGGGAGAGTGAAGTGAGCTGGCAGTACCCC
ATGTCTGAAGAAGAGAGCTCCGATGTGGAAATCAGAAATGAAGAAAACAACAGCGGCCTT
TTTGTGACGGTCTTGGAAGTGAGCAGTGCCTCGGCGGCCCACACAGGGTTGTACACTTGC
TATTACAACCACACTCAGACAGAAGAGAATGAGCTTGAAGGCAGGCACATTTACATCTAT
GTGCCAGACCCAGATGTAGCCTTTGTACCTCTAGGAATGACGGATTATTTAGTCATCGTG
GAGGATGATGATTCTGCCATTATACCTTGTCGCACAACTGATCCCGAGACTCCTGTAACC
TTACACAACAGTGAGGGGGTGGTACCTGCCTCCTACGACAGCAGACAGGGCTTTAATGGG
ACCTTCACTGTAGGGCCCTATATCTGTGAGGCCACCGTCAAAGGAAAGAAGTTCCAGACC
ATCCCATTTAATGTTTATGCTTTAAAAGCAACATCAGAGCTGGATCTAGAAATGGAAGCT
CTTAAAACCGTGTATAAGTCAGGGGAAACGATTGTGGTCACCTGTGCTGTTTTTAACAAT
GAGGTGGTTGACCTTCAATGGACTTACCCTGGAGAAGTGAAAGGCAAAGGCATCACAATG
CTGGAAGAAATCAAAGTCCCATCCATCAAATTGGTGTACACTTTGACGGTCCCCGAGGCC
ACGGTGAAAGACAGTGGAGATTACGAATGTGCTGCCCGCCAGGCTACCAGGGAGGTCAAA
GAAATGAAGAAAGTCACTATTTCTGTCCATGAGAAAGGTTTCATTGAAATCAAACCCACC
TTCAGCCAGTTGGAAGCTGTCAACCTGCATGAAGTCAAACATTTTGTTGTAGAGGTGCGG
GCCTACCCACCTCCCAGGATATCCTGGCTGAAAAACAATCTGACTCTGATTGAAAATCTC
ACTGAGATCACCACTGATGTGGAAAAGATTCAGGAAATAAGGTATCGAAGCAAATTAAAG
CTGATCCGTGCTAAGGAAGAAGACAGTGGCCATTATACTATTGTAGCTCAAAATGAAGAT
GCTGTGAAGAGCTATACTTTTGAACTGTTAACTCAAGTTCCTTCATCCATTCTGGACTTG
GTCGATGATCACCATGGCTCAACTGGGGGACAGACGGTGAGGTGCACAGCTGAAGGCACG
CCGCTTCCTGATATTGAGTGGATGATATGCAAAGATATTAAGAAATGTAATAATGAAACT
TCCTGGACTATTTTGGCCAACAATGTCTCAAACATCATCACGGAGATCCACTCCCGAGAC
AGGAGTACCGTGGAGGGCCGTGTGACTTTCGCCAAAGTGGAGGAGACCATCGCCGTGCGA
TGCCTGGCTAAGAATCTCCTTGGAGCTGAGAACCGAGAGCTGAAGCTGGTGGCTCCCACC
CTGCGTTCTGAACTCACGGTGGCTGCTGCAGTCCTGGTGCTGTTGGTGATTGTGATCATC
TCACTTATTGTCCTGGTTGTCATTTGGAAACAGAAACCGAGGTATGAAATTCGCTGGAGG
GTCATTGAATCAATCAGCCCGGATGGACATGAATATATTTATGTGGACCCGATGCAGCTG
CCTTATGACTCAAGATGGGAGTTTCCAAGAGATGGACTAGTGCTTGGTCGGGTCTTGGGG
TCTGGAGCGTTTGGGAAGGTGGTTGAAGGAACAGCCTATGGATTAAGCCGGTCCCAACCT
GTCATGAAAGTTGCAGTGAAGATGCTAAAACCCACGGCCAGATCCAGTGAAAAACAAGCT
CTCATGTCTGAACTGAAGATAATGACTCACCTGGGGCCACATTTGAACATTGTAAACTTG
CTGGGAGCCTGCACCAAGTCAGGCCCCATTTACATCATCACAGAGTATTGCTTCTATGGA
GATTTGGTCAACTATTTGCATAAGAATAGGGATAGCTTCCTGAGCCACCACCCAGAGAAG
CCAAAGAAAGAGCTGGATATCTTTGGATTGAACCCTGCTGATGAAAGCACACGGAGCTAT
GTTATTTTATCTTTTGAAAACAATGGTGACTACATGGACATGAAGCAGGCTGATACTACA
CAGTATGTCCCCATGCTAGAAAGGAAAGAGGTTTCTAAATATTCCGACATCCAGAGATCA
CTCTATGATCGTCCAGCCTCATATAAGAAGAAATCTATGTTAGACTCAGAAGTCAAAAAC
CTCCTTTCAGATGATAACTCAGAAGGCCTTACTTTATTGGATTTGTTGAGCTTCACCTAT
CAAGTTGCCCGAGGAATGGAGTTTTTGGCTTCAAAAAATTGTGTCCACCGTGATCTGGCT
GCTCGCAACGTCCTCCTGGCACAAGGAAAAATTGTGAAGATCTGTGACTTTGGCCTGGCC
AGAGACATCATGCATGATTCGAACTATGTGTCGAAAGGCAGTACCTTTCTGCCCGTGAAG
TGGATGGCTCCTGAGAGCATCTTTGACAACCTCTACACCACACTGAGTGATGTCTGGTCT
TATGGCATTCTGCTCTGGGAGATCTTTTCCCTTGGTGGCACCCCTTACCCCGGCATGATG
GTGGATTCTACTTTCTACAATAAGATCAAGAGTGGGTACCGGATGGCCAAGCCTGACCAC
GCTACCAGTGAAGTCTACGAGATCATGGTGAAATGCTGGAACAGTGAGCCGGAGAAGAGA
CCCTCCTTTTACCACCTGAGTGAGATTGTGGAGAATCTGCTGCCTGGACAATATAAAAAG
AGTTATGAAAAAATTCACCTGGACTTCCTGAAGAGTGACCATCCTGCTGTGGCACGCATG
CGTGTGGACTCAGACAATGCATACATTGGTGTCACCTACAAAAACGAGGAAGACAAGCTG
AAGGACTGGGAGGGTGGTCTGGATGAGCAGAGACTGAGCGCTGACAGTGGCTACATCATT
CCTCTGCCTGACATTGACCCTGTCCCTGAGGAGGAGGACCTGGGCAAGAGGAACAGACAC
AGCTCGCAGACCTCTGAAGAGAGTGCCATTGAGACGGGTTCCAGCAGTTCCACCTTCATC
AAGAGAGAGGACGAGACCATTGAAGACATCGACATGATGGACGACATCGGCATAGACTCT
TCAGACCTGGTGGAAGACAGCTTCCTGTAA

1. Karthikeyan S, Leung T, Ladias JA: Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors. J Biol Chem. 2002 May 24;277(21):18973-8. Epub 2002 Mar 6. [PubMed ]
2. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003 Mar 27;348(13):1201-14. [PubMed ]
3. Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S: Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989 Feb 10;243(4892):800-4. [PubMed ]
4. Claesson-Welsh L, Eriksson A, Westermark B, Heldin CH: cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4917-21. [PubMed ]
5. Kawagishi J, Kumabe T, Yoshimoto T, Yamamoto T: Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA. Genomics. 1995 Nov 20;30(2):224-32. [PubMed ]

1. Yi ES, Strong CR, Piao Z, Perucho M, Weidner N: Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity. Appl Immunohistochem Mol Morphol. 2005 Jun;13(2):157-61. [PubMed ]
2. Borbenyi Z: [Disorders with eosinophilia, treatment of hypereosinophilic syndrome] Orv Hetil. 2005 May 1;146(18 Suppl 1):911-6. [PubMed ]
3. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC: PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005 Aug 10;23(23):5357-64. Epub 2005 May 31. [PubMed ]
4. Chen LL, Sabripour M, Andtbacka RH, Patel SR, Feig BW, Macapinlac HA, Choi H, Wu EF, Frazier ML, Benjamin RS: Imatinib resistance in gastrointestinal stromal tumors. Curr Oncol Rep. 2005 Jul;7(4):293-9. [PubMed ]
5. Tefferi A: Modern diagnosis and treatment of primary eosinophilia. Acta Haematol. 2005;114(1):52-60. [PubMed ]

1. CD115 antigen
2. CSF-1-R
3. EC 2.7.10.1
4. Fms proto-oncogene
5. Macrophage colony-stimulating factor 1 receptor precursor
6. c-fms

MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTL
YSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFED
QDALLPCLLTDPVLEAGVSLVRVRGRPLMRHTNYSFSPWHGFTIHRAKFIQSQDYQCSAL
MGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASSVDVNFDVFLQHN
NTKLAIPQQSDFHNNRYQKVLTLNLDQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAY
LNLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTY
RHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTFINGSGTLLCA
ASGYPQPNVTWLQCSGHTDRCDEAQVLQVWDDPYPEVLSQEPFHKVTVQSLLTVETLEHN
QTYECRAHNSVGSGSWAFIPISAGAHTHPPDEFLFTPVVVACMSIMALLLLLLLLLLYKY
KQKPKYQVRWKIIESYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEAT
AFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVL
VITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKNIHLEKKYVRRDSGFSSQGV
DTYVEMRPVSTSSNDSFSEQDLDKEDGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVA
ARNVLLTNGHVAKIGDFGLARDIMNDSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWS
YGILLWEIFSLGLNPYPGILVNSKFYKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHR
PTFQQICSFLQEQAQEDRRERDYTNLPSSSRSGGSGSSSSELEEESSSEHLTCCEQGDIA
QPLLQPNNYQFC

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• ig (PF00047 )
• V-set (PF07686 )
• Pkinase_Tyr (PF07714 )

• 1-19

• 513-537

• Membrane
• single-pass type I membrane protein

ATGGGCCCAGGAGTTCTGCTGCTCCTGCTGGTGGCCACAGCTTGGCATGGTCAGGGAATC
CCAGTGATAGAGCCCAGTGTCCCCGAGCTGGTCGTGAAGCCAGGAGCAACGGTGACCTTG
CGATGTGTGGGCAATGGCAGCGTGGAATGGGATGGCCCCCCATCACCTCACTGGACCCTG
TACTCTGATGGCTCCAGCAGCATCCTCAGCACCAACAACGCTACCTTCCAAAACACGGGG
ACCTATCGCTGCACTGAGCCTGGAGACCCCCTGGGAGGCAGCGCCGCCATCCACCTCTAT
GTCAAAGACCCTGCCCGGCCCTGGAACGTGCTAGCACAGGAGGTGGTCGTGTTCGAGGAC
CAGGACGCACTACTGCCCTGTCTGCTCACAGACCCGGTGCTGGAAGCAGGCGTCTCGCTG
GTGCGTGTGCGTGGCCGGCCCCTCATGCGCCACACCAACTACTCCTTCTCGCCCTGGCAT
GGCTTCACCATCCACAGGGCCAAGTTCATTCAGAGCCAGGACTATCAATGCAGTGCCCTG
ATGGGTGGCAGGAAGGTGATGTCCATCAGCATCCGGCTGAAAGTGCAGAAAGTCATCCCA
GGGCCCCCAGCCTTGACACTGGTGCCTGCAGAGCTGGTGCGGATTCGAGGGGAGGCTGCC
CAGATCGTGTGCTCAGCCAGCAGCGTTGATGTTAACTTTGATGTCTTCCTCCAACACAAC
AACACCAAGCTCGCAATCCCTCAACAATCTGACTTTCATAATAACCGTTACCAAAAAGTC
CTGACCCTCAACCTCGATCAAGTAGATTTCCAACATGCCGGCAACTACTCCTGCGTGGCC
AGCAACGTGCAGGGCAAGCACTCCACCTCCATGTTCTTCCGGGTGGTAGAGAGTGCCTAC
TTGAACTTGAGCTCTGAGCAGAACCTCATCCAGGAGGTGACCGTGGGGGAGGGGCTCAAC
CTCAAAGTCATGGTGGAGGCCTACCCAGGCCTGCAAGGTTTTAACTGGACCTACCTGGGA
CCCTTTTCTGACCACCAGCCTGAGCCCAAGCTTGCTAATGCTACCACCAAGGACACATAC
AGGCACACCTTCACCCTCTCTCTGCCCCGCCTGAAGCCCTCTGAGGCTGGCCGCTACTCC
TTCCTGGCCAGAAACCCAGGAGGCTGGAGAGCTCTGACGTTTGAGCTCACCCTTCGATAC
CCCCCAGAGGTAAGCGTCATATGGACATTCATCAACGGCTCTGGCACCCTTTTGTGTGCT
GCCTCTGGGTACCCCCAGCCCAACGTGACATGGCTGCAGTGCAGTGGCCACACTGATAGG
TGTGATGAGGCCCAAGTGCTGCAGGTCTGGGATGACCCATACCCTGAGGTCCTGAGCCAG
GAGCCCTTCCACAAGGTGACGGTGCAGAGCCTGCTGACTGTTGAGACCTTAGAGCACAAC
CAAACCTACGAGTGCAGGGCCCACAACAGCGTGGGGAGTGGCTCCTGGGCCTTCATACCC
ATCTCTGCAGGAGCCCACACGCATCCCCCGGATGAGTTCCTCTTCACACCAGTGGTGGTC
GCCTGCATGTCCATCATGGCCTTGCTGCTGCTGCTGCTCCTGCTGCTATTGTACAAGTAT
AAGCAGAAGCCCAAGTACCAGGTCCGCTGGAAGATCATCGAGAGCTATGAGGGCAACAGT
TATACTTTCATCGACCCCACGCAGCTGCCTTACAACGAGAAGTGGGAGTTCCCCCGGAAC
AACCTGCAGTTTGGTAAGACCCTCGGAGCTGGAGCCTTTGGGAAGGTGGTGGAGGCCACG
GCCTTTGGTCTGGGCAAGGAGGATGCTGTCCTGAAGGTGGCTGTGAAGATGCTGAAGTCC
ACGGCCCATGCTGATGAGAAGGAGGCCCTCATGTCCGAGCTGAAGATCATGAGCCACCTG
GGCCAGCACGAGAACATCGTCAACCTTCTGGGAGCCTGTACCCATGGAGGCCCTGTACTG
GTCATCACGGAGTACTGTTGCTATGGCGACCTGCTCAACTTTCTGCGAAGGAAGGCTGAG
GCCATGCTGGGACCCAGCCTGAGCCCCGGCCAGGACCCCGAGGGAGGCGTCGACTATAAG
AACATCCACCTCGAGAAGAAATATGTCCGCAGGGACAGTGGCTTCTCCAGCCAGGGTGTG
GACACCTATGTGGAGATGAGGCCTGTCTCCACTTCTTCAAATGACTCCTTCTCTGAGCAA
GACCTGGACAAGGAGGATGGACGGCCCCTGGAGCTCCGGGACCTGCTTCACTTCTCCAGC
CAAGTAGCCCAGGGCATGGCCTTCCTCGCTTCCAAGAATTGCATCCACCGGGACGTGGCA
GCGCGTAACGTGCTGTTGACCAATGGTCATGTGGCCAAGATTGGGGACTTCGGGCTGGCT
AGGGACATCATGAATGACTCCAACTACATTGTCAAGGGCAATGCCCGCCTGCCTGTGAAG
TGGATGGCCCCAGAGAGCATCTTTGACTGTGTCTACACGGTTCAGAGCGACGTCTGGTCC
TATGGCATCCTCCTCTGGGAGATCTTCTCACTTGGGCTGAATCCCTACCCTGGCATCCTG
GTGAACAGCAAGTTCTATAAACTGGTGAAGGATGGATACCAAATGGCCCAGCCTGCATTT
GCCCCAAAGAATATATACAGCATCATGCAGGCCTGCTGGGCCTTGGAGCCCACCCACAGA
CCCACCTTCCAGCAGATCTGCTCCTTCCTTCAGGAGCAGGCCCAAGAGGACAGGAGAGAG
CGGGACTATACCAATCTGCCGAGCAGCAGCAGAAGCGGTGGCAGCGGCAGCAGCAGCAGT
GAGCTGGAGGAGGAGAGCTCTAGTGAGCACCTGACCTGCTGCGAGCAAGGGGATATCGCC
CAGCCCTTGCTGCAGCCCAACAACTATCAGTTCTGCTGA

1. Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM, Ullrich A: Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20-26;320(6059):277-80. [PubMed ]
2. Hampe A, Shamoon BM, Gobet M, Sherr CJ, Galibert F: Nucleotide sequence and structural organization of the human FMS proto-oncogene. Oncogene Res. 1989;4(1):9-17. [PubMed ]
3. Visvader J, Verma IM: Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes. Mol Cell Biol. 1989 Mar;9(3):1336-41. [PubMed ]
4. Wheeler EF, Roussel MF, Hampe A, Walker MH, Fried VA, Look AT, Rettenmier CW, Sherr CJ: The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences. J Virol. 1986 Aug;59(2):224-33. [PubMed ]
5. Browning PJ, Bunn HF, Cline A, Shuman M, Nienhuis AW: "Replacement" of COOH-terminal truncation of v-fms with c-fms sequences markedly reduces transformation potential. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7800-4. [PubMed ]
6. Nienhuis AW, Bunn HF, Turner PH, Gopal TV, Nash WG, O'Brien SJ, Sherr CJ: Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome. Cell. 1985 Sep;42(2):421-8. [PubMed ]
7. Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F: Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. Genomics. 1997 Jan 15;39(2):216-26. [PubMed ]

1. Dewar AL, Zannettino AC, Hughes TP, Lyons AB: Inhibition of c-fms by imatinib: expanding the spectrum of treatment. Cell Cycle. 2005 Jul;4(7):851-3. Epub 2005 Jul 28. [PubMed ]
2. Taylor JR, Brownlow N, Domin J, Dibb NJ: FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. Oncogene. 2006 Jan 5;25(1):147-51. [PubMed ]
3. Dewar AL, Farrugia AN, Condina MR, Bik To L, Hughes TP, Vernon-Roberts B, Zannettino AC: Imatinib as a potential antiresorptive therapy for bone disease. Blood. 2006 Jun 1;107(11):4334-7. Epub 2006 Jan 31. [PubMed ]
4. Ando W, Hashimoto J, Nampei A, Tsuboi H, Tateishi K, Ono T, Nakamura N, Ochi T, Yoshikawa H: Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA). J Bone Miner Metab. 2006;24(4):274-82. [PubMed ]
5. El Hajj Dib I, Gallet M, Mentaverri R, Sevenet N, Brazier M, Kamel S: Imatinib mesylate (Gleevec) enhances mature osteoclast apoptosis and suppresses osteoclast bone resorbing activity. Eur J Pharmacol. 2006 Dec 3;551(1-3):27-33. Epub 2006 Sep 16. [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. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, Schellens JH: The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005 Apr 1;65(7):2577-82. [PubMed ]
2. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters] Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [PubMed ]
3. Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, de Boeck G, Sparreboom A, Verweij J, Nooter K: Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52. Epub 2005 Jul 9. [PubMed ]
4. Galimberti S, Cervetti G, Guerrini F, Testi R, Pacini S, Fazzi R, Simi P, Petrini M: Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment. Cancer Genet Cytogenet. 2005 Oct 1;162(1):57-62. [PubMed ]
5. Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, Prenen H, de Jong FA, Baker SD, Bates SE, Figg WD, Verweij J, Sparreboom A, Nooter K: Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006 Aug;80(2):192-201. [PubMed ]

1. EC 2.7.10.1
2. High affinity nerve growth factor receptor precursor
3. Neurotrophic tyrosine kinase receptor type 1
4. TRK1 transforming tyrosine kinase protein
5. Trk-A
6. p140-TrkA

MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLH
HLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL
NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ
GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMK
SGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWC
IPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT
LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSV
AVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTE
GKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML
VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRF
LRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQ
GLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI
FTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHAR
LQALAQAPPVYLDVLG

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• LRR_1 (PF00560 )
• Pkinase_Tyr (PF07714 )

• 1-32

• 424-439

• Cell membrane
• single-pass type I membrane protein. Note=Endocytosed to the endosomes upon treatment

ATGCTGCGAGGCGGACGGCGCGGGCAGCTTGGCTGGCACAGCTGGGCTGCGGGGCCGGGC
AGCCTGCTGGCTTGGCTGATACTGGCATCTGCGGGCGCCGCACCCTGCCCCGATGCCTGC
TGCCCCCACGGCTCCTCGGGACTGCGATGCACCCGGGATGGGGCCCTGGATAGCCTCCAC
CACCTGCCCGGCGCAGAGAACCTGACTGAGCTCTACATCGAGAACCAGCAGCATCTGCAG
CATCTGGAGCTCCGTGATCTGAGGGGCCTGGGGGAGCTGAGAAACCTCACCATCGTGAAG
AGTGGTCTCCGTTTCGTGGCGCCAGATGCCTTCCATTTCACTCCTCGGCTCAGTCGCCTG
AATCTCTCCTTCAACGCTCTGGAGTCTCTCTCCTGGAAAACTGTGCAGGGCCTCTCCTTA
CAGGAACTGGTCCTGTCGGGGAACCCTCTGCACTGTTCTTGTGCCCTGCGCTGGCTACAG
CGCTGGGAGGAGGAGGGACTGGGCGGAGTGCCTGAACAGAAGCTGCAGTGTCATGGGCAA
GGGCCCCTGGCCCACATGCCCAATGCCAGCTGTGGTGTGCCCACGCTGAAGGTCCAGGTG
CCCAATGCCTCGGTGGATGTGGGGGACGACGTGCTGCTGCGGTGCCAGGTGGAGGGGCGG
GGCCTGGAGCAGGCCGGCTGGATCCTCACAGAGCTGGAGCAGTCAGCCACGGTGATGAAA
TCTGGGGGTCTGCCATCCCTGGGGCTGACCCTGGCCAATGTCACCAGTGACCTCAACAGG
AAGAACTTGACGTGCTGGGCAGAGAACGATGTGGGCCGGGCAGAGGTCTCTGTTCAGGTC
AACGTCTCCTTCCCGGCCAGTGTGCAGCTGCACACGGCGGTGGAGATGCACCACTGGTCG
ATCCCCTTCTCTGTGGATGGGCAGCCGGCACCGTCTCTGCGCTGGCTCTTCAATGGCTCC
GTGCTCAATGAGACCAGCTTCATCTTCACTGAGTTCCTGGAGCCGGCAGCCAATGAGACC
GTGCGGCACGGGTGTCTGCGCCTCAACCAGCCCACCCACGTCAACAACGGCAACTACACG
CTGCTGGCTGCCAACCCCTTCGGCCAGGCCTCCGCCTCCATCATGGCTGCCTTCATGGAC
AACCCTTTCGAGTTCAACCCCGAGGACCCCATCCCTGACACTAACAGCACATCTGGAGAC
CCGGTGGAGAAGAAGGACGAAACACCTTTTGGGGTCTCGGTGGCTGTGGGCCTGGCCGTC
TTTGCCTGCCTCTTCCTTTCTACGCTGCTCCTTGTGCTCAACAAATGTGGACGGAGAAAC
AAGTTTGGGATCAACCGCCCGGCTGTGCTGGCTCCAGAGGATGGGCTGGCCATGTCCCTG
CATTTCATGACATTGGGTGGCAGCTCCCTGTCCCCCACCGAGGGCAAAGGCTCTGGGCTC
CAAGGCCACATCATCGAGAACCCACAATACTTCAGTGATGCCTGTGTTCACCACATCAAG
CGCCGGGACATCGTGCTCAAGTGGGAGCTGGGGGAGGGCGCCTTTGGGAAGGTCTTCCTT
GCTGAGTGCCACAACCTCCTGCCTGAGCAGGACAAGATGCTGGTGGCTGTCAAGGCACTG
AAGGAGGCGTCCGAGAGTGCTCGGCAGGACTTCCAACGTGAGGCTGAGCTGCTCACCATG
CTGCAGCACCAGCACATCGTGCGCTTCTTCGGCGTCTGCACCGAGGGCCGCCCCCTGCTC
ATGGTCTTCGAGTATATGCGGCACGGGGACCTCAACCGCTTCCTCCGATCCCATGGACCC
GATGCCAAGCTGCTGGCTGGTGGGGAGGATGTGGCTCCAGGCCCCCTGGGTCTGGGGCAG
CTGCTGGCCGTGGCTAGCCAGGTCGCTGCGGGGATGGTGTACCTGGCGGGTCTGCATTTT
GTGCACCGGGACCTGGCCACACGCAACTGTCTAGTGGGCCAGGGACTGGTGGTCAAGATT
GGTGATTTTGGCATGAGCAGGGATATCTACAGCACCGACTATTACCGTGTGGGAGGCCGC
ACCATGCTGCCCATTCGCTGGATGCCGCCCGAGAGCATCCTGTACCGTAAGTTCACCACC
GAGAGCGACGTGTGGAGCTTCGGCGTGGTGCTCTGGGAGATCTTCACCTACGGCAAGCAG
CCCTGGTACCAGCTCTCCAACACGGAGGCAATCGACTGCATCACGCAGGGACGTGAGTTG
GAGCGGCCACGTGCCTGCCCACCAGAGGTCTACGCCATCATGCGGGGCTGCTGGCAGCGG
GAGCCCCAGCAACGCCACAGCATCAAGGATGTGCACGCCCGGCTGCAAGCCCTGGCCCAG
GCACCTCCTGTCTACCTGGATGTCCTGGGCTAG

1. Greco A, Villa R, Tubino B, Romano L, Penso D, Pierotti MA: A novel NTRK1 mutation associated with congenital insensitivity to pain with anhidrosis. Am J Hum Genet. 1999 Apr;64(4):1207-10. [PubMed ]
2. Yotsumoto S, Setoyama M, Hozumi H, Mizoguchi S, Fukumaru S, Kobayashi K, Saheki T, Kanzaki T: A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis. J Invest Dermatol. 1999 May;112(5):810-4. [PubMed ]
3. Mardy S, Miura Y, Endo F, Matsuda I, Sztriha L, Frossard P, Moosa A, Ismail EA, Macaya A, Andria G, Toscano E, Gibson W, Graham GE, Indo Y: Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am J Hum Genet. 1999 Jun;64(6):1570-9. [PubMed ]
4. 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 ]
5. Gimm O, Greco A, Hoang-Vu C, Dralle H, Pierotti MA, Eng C: Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma. J Clin Endocrinol Metab. 1999 Aug;84(8):2784-7. [PubMed ]
6. Greco A, Villa R, Fusetti L, Orlandi R, Pierotti MA: The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor. J Cell Physiol. 2000 Jan;182(1):127-33. [PubMed ]
7. Shatzky S, Moses S, Levy J, Pinsk V, Hershkovitz E, Herzog L, Shorer Z, Luder A, Parvari R: Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies. Am J Med Genet. 2000 Jun 19;92(5):353-60. [PubMed ]
8. Miura Y, Mardy S, Awaya Y, Nihei K, Endo F, Matsuda I, Indo Y: Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families. Hum Genet. 2000 Jan;106(1):116-24. [PubMed ]
9. Klein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M: The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189-97. [PubMed ]
10. Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV: High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678-83. [PubMed ]
11. 2869410 Martin-Zanca D, Hughes SH, Barbacid M: A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature. 1986 Feb 27-Mar 5;319(6056):743-8.
12. 2927393 Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M: Molecular and biochemical characterization of the human trk proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):24-33.
13. 2966065 Kozma SC, Redmond SM, Fu XC, Saurer SM, Groner B, Hynes NE: Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences. EMBO J. 1988 Jan;7(1):147-54.
14. 7510697 Loeb DM, Stephens RM, Copeland T, Kaplan DR, Greene LA: A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not neurite outgrowth. J Biol Chem. 1994 Mar 25;269(12):8901-10.
15. 7565764 Greco A, Mariani C, Miranda C, Lupas A, Pagliardini S, Pomati M, Pierotti MA: The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. Mol Cell Biol. 1995 Nov;15(11):6118-27.
16. 7823156 Shelton DL, Sutherland J, Gripp J, Camerato T, Armanini MP, Phillips HS, Carroll K, Spencer SD, Levinson AD: Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins. J Neurosci. 1995 Jan;15(1 Pt 2):477-91.
17. 8155326 Stephens RM, Loeb DM, Copeland TD, Pawson T, Greene LA, Kaplan DR: Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses. Neuron. 1994 Mar;12(3):691-705.
18. 8325889 Barker PA, Lomen-Hoerth C, Gensch EM, Meakin SO, Glass DJ, Shooter EM: Tissue-specific alternative splicing generates two isoforms of the trkA receptor. J Biol Chem. 1993 Jul 15;268(20):15150-7.
19. 8524391 Zhou MM, Ravichandran KS, Olejniczak EF, Petros AM, Meadows RP, Sattler M, Harlan JE, Wade WS, Burakoff SJ, Fesik SW: Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature. 1995 Dec 7;378(6557):584-92.
20. 8696348 Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K, Kawano T, Mitsubuchi H, Tonoki H, Awaya Y, Matsuda I: Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat Genet. 1996 Aug;13(4):485-8.
21. 9290260 Indo Y, Mardy S, Tsuruta M, Karim MA, Matsuda I: Structure and organization of the human TRKA gene encoding a high affinity receptor for nerve growth factor. Jpn J Hum Genet. 1997 Jun;42(2):343-51.

1. Catani M, De Milito R, Simi M: [New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location] Chir Ital. 2005 Jan-Feb;57(1):127-33. [PubMed ]
2. Kovacs M, Nagy P, Pak G, Feher J: [Gastrointestinal stromal tumors (GISTs): clinical and pathological features] Orv Hetil. 2005 Jun 26;146(26):1375-81. [PubMed ]
3. de Groot JW, Plaza Menacho I, Schepers H, Drenth-Diephuis LJ, Osinga J, Plukker JT, Links TP, Eggen BJ, Hofstra RM: Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery. 2006 Jun;139(6):806-14. [PubMed ]
4. de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ, Voest EE: A Phase II Trial of Imatinib Therapy for Metastatic Medullary Thyroid Carcinoma. J Clin Endocrinol Metab. 2007 Sep;92(9):3466-9. Epub 2007 Jun 19. [PubMed ]
5. Delbaldo C: [Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)] Therapie. 2007 Mar-Apr;62(2):87-90. Epub 2007 Jun 21. [PubMed ]

1. Breast cancer resistance protein
2. CD338 antigen
3. CDw338
4. Mitoxantrone resistance-associated protein
5. Placenta-specific ATP- binding cassette transporter

MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKSGFLPCRKPVE
KEILSNINGIMKPGLNAILGPTGGGKSSLLDVLAARKDPSGLSGDVLINGAPRPANFKCN
SGYVVQDDVVMGTLTVRENLQFSAALRLATTMTNHEKNERINRVIQELGLDKVADSKVGT
QFIRGVSGGERKRTSIGMELITDPSILFLDEPTTGLDSSTANAVLLLLKRMSKQGRTIIF
SIHQPRYSIFKLFDSLTLLASGRLMFHGPAQEALGYFESAGYHCEAYNNPADFFLDIING
DSTAVALNREEDFKATEIIEPSKQDKPLIEKLAEIYVNSSFYKETKAELHQLSGGEKKKK
ITVFKEISYTTSFCHQLRWVSKRSFKNLLGNPQASIAQIIVTVVLGLVIGAIYFGLKNDS
TGIQNRAGVLFFLTTNQCFSSVSAVELFVVEKKLFIHEYISGYYRVSSYFLGKLLSDLLP
MRMLPSIIFTCIVYFMLGLKPKADAFFVMMFTLMMVAYSASSMALAIAAGQSVVSVATLL
MTICFVFMMIFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGN
NPCNYATCTGEEYLVKQGIDLSPWGLWKNHVALACMIVIFLTIAYLKLLFLKKYS

• ABC_tran (PF00005 )
• ABC2_membrane (PF01061 )

• None

• 396-416
• 429-449
• 478-498
• 507-527
• 536-556
• 631-651

• Cell membrane
• multi-pass membrane protein

ATGTCTTCCAGTAATGTCGAAGTTTTTATCCCAGTGTCACAAGGAAACACCAATGGCTTC
CCCGCGACAGTTTCCAATGACCTGAAGGCATTTACTGAAGGAGCTGTGTTAAGTTTTCAT
AACATCTGCTATCGAGTAAAACTGAAGAGTGGCTTTCTACCTTGTCGAAAACCAGTTGAG
AAAGAAATATTATCGAATATCAATGGGATCATGAAACCTGGTCTCAACGCCATCCTGGGA
CCCACAGGTGGAGGCAAATCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAGT
GGATTATCTGGAGATGTTCTGATAAATGGAGCACCGCGACCTGCCAATTTCAAATGTAAT
TCAGGTTACGTGGTACAAGATGATGTTGTGATGGGCACTCTGACGGTGAGAGAAAACTTA
CAGTTCTCAGCAGCTCTTCGGCTTGCAACAACTATGACGAATCATGAAAAAAACGAACGG
ATTAACAGGGTCATTGAAGAGTTAGGTCTGGATAAAGTGGCAGACTCCAAGGTTGGAACT
CAGTTTATCCGTGGTGTGTCTGGAGGAGAAAGAAAAAGGACTAGTATAGGAATGGAGCTT
ATCACTGATCCTTCCATCTTGTCCTTGGATGAGCCTACAACTGGCTTAGACTCAAGCACA
GCAAATGCTGTCCTTTTGCTCCTGAAAAGGATGTCTAAGCAGGGACGAACAATCATCTTC
TCCATTCATCAGCCTCGATATTCCATCTTCAAGTTGTTTGATAGCCTCACCTTATTGGCC
TCAGGAAGACTTATGTTCCACGGGCCTGCTCAGGAGGCCTTGGGATACTTTGAATCAGCT
GGTTATCACTGTGAGGCCTATAATAACCCTGCAGACTTCTTCTTGGACATCATTAATGGA
GATTCCACTGCTGTGGCATTAAACAGAGAAGAAGACTTTAAAGCCACAGAGATCATAGAG
CCTTCCAAGCAGGATAAGCCACTCATAGAAAAATTAGCGGAGATTTATGTCAACTCCTCC
TTCTACAAAGAGACAAAAGCTGAATTACATCAACTTTCCGGGGGTGAGAAGAAGAAGAAG
ATCACAGTCTTCAAGGAGATCAGCTACACCACCTCCTTCTGTCATCAACTCAGATGGGTT
TCCAAGCGTTCATTCAAAAACTTGCTGGGTAATCCCCAGGCCTCTATAGCTCAGATCATT
GTCACAGTCGTACTGGGACTGGTTATAGGTGCCATTTACTTTGGGCTAAAAAATGATTCT
ACTGGAATCCAGAACAGAGCTGGGGTTCTCTTCTTCCTGACGACCAACCAGTGTTTCAGC
AGTGTTTCAGCCGTGGAACTCTTTGTGGTAGAGAAGAAGCTCTTCATACATGAATACATC
AGCGGATACTACAGAGTGTCATCTTATTTCCTTGGAAAACTGTTATCTGATTTATTACCC
ATGAGGATGTTACCAAGTATTATATTTACCTGTATAGTGTACTTCATGTTAGGATTGAAG
CCAAAGGCAGATGCCTTCTTCGTTATGATGTTTACCCTTATGATGGTGGCTTATTCAGCC
AGTTCCATGGCACTGGCCATAGCAGCAGGTCAGAGTGTGGTTTCTGTAGCAACACTTCTC
ATGACCATCTGTTTTGTGTTTATGATGATTTTTTCAGGTCTGTTGGTCAATCTCACAACC
ATTGCATCTTGGCTGTCATGGCTTCAGTACTTCAGCATTCCACGATATGGATTTACGGCT
TTGCAGCATAATGAATTTTTGGGACAAAACTTCTGCCCAGGACTCAATGCAACAGGAAAC
AATCCTTGTAACTATGCAACATGTACTGGCGAAGAATATTTGGTAAAGCAGGGCATCGAT
CTCTCACCCTGGGGCTTGTGGAAGAATCACGTGGCCTTGGCTTGTATGATTGTTATTTTC
CTCACAATTGCCTACCTGAAATTGTTATTTCTTAAAAAATATTCTTAA

1. Komatani H, Kotani H, Hara Y, Nakagawa R, Matsumoto M, Arakawa H, Nishimura S: Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 2001 Apr 1;61(7):2827-32. [PubMed ]
2. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001 Sep;7(9):1028-34. [PubMed ]
3. Schmitz G, Langmann T, Heimerl S: Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res. 2001 Oct;42(10):1513-20. [PubMed ]
4. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, Harigae S, Osawa S, Nakamura Y: Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J Hum Genet. 2002;47(6):285-310. [PubMed ]
5. Zhang W, Mojsilovic-Petrovic J, Andrade MF, Zhang H, Ball M, Stanimirovic DB: The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 2003 Nov;17(14):2085-7. Epub 2003 Sep 4. [PubMed ]
6. Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 1998 Dec 1;58(23):5337-9. [PubMed ]
7. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. [PubMed ]

1. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, Schellens JH: The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005 Apr 1;65(7):2577-82. [PubMed ]
2. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters] Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [PubMed ]
3. Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, de Boeck G, Sparreboom A, Verweij J, Nooter K: Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52. Epub 2005 Jul 9. [PubMed ]
4. Yanase K, Tsukahara S, Mitsuhashi J, Sugimoto Y: Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. Cancer Lett. 2006 Mar 8;234(1):73-80. Epub 2005 Nov 21. [PubMed ]
5. Nakanishi T, Shiozawa K, Hassel BA, Ross DD: Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib-induced reduction of BCRP expression. Blood. 2006 Jul 15;108(2):678-84. Epub 2006 Mar 16. [PubMed ]

1. Fragment

GEGDVRCRGAASAVAAAAAAARQ

• None

• None

ATGGCGAAGGCGACGTCCGGTGCCGCGGGGCTGCGTCTGCTGTTGCTGCTGCTGCTGCCG
CTGCTAGGCAAAG

1. Patrone G, Puliti A, Bocciardi R, Ravazzolo R, Romeo G: Sequence and characterisation of the RET proto-oncogene 5' flanking region: analysis of retinoic acid responsiveness at the transcriptional level. FEBS Lett. 1997 Dec 8;419(1):76-82. [PubMed ]
2. Munnes M, Patrone G, Schmitz B, Romeo G, Doerfler W: A 5'-CG-3'-rich region in the promoter of the transcriptionally frequently silenced RET protooncogene lacks methylated cytidine residues. Oncogene. 1998 Nov 19;17(20):2573-83. [PubMed ]

1. de Groot JW, Plaza Menacho I, Schepers H, Drenth-Diephuis LJ, Osinga J, Plukker JT, Links TP, Eggen BJ, Hofstra RM: Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery. 2006 Jun;139(6):806-14. [PubMed ]

1. CD167a antigen
2. Cell adhesion kinase
3. Discoidin receptor tyrosine kinase
4. EC 2.7.10.1
5. Epithelial discoidin domain receptor 1
6. Epithelial discoidin domain-containing receptor 1 precursor
7. HGK2
8. Protein-tyrosine kinase RTK 6
9. TRK E
10. Tyrosine kinase DDR
11. Tyrosine-protein kinase CAK

MGPEALSSLLLLLLVASGDADMKGHFDPAKCRYALGMQDRTIPDSDISASSSWSDSTAAR
HSRLESSDGDGAWCPAGSVFPKEEEYLQVDLQRLHLVALVGTQGRHAGGLGKEFSRSYRL
RYSRDGRRWMGWKDRWGQEVISGNEDPEGVVLKDLGPPMVARLVRFYPRADRVMSVCLRV
ELYGCLWRDGLLSYTAPVGQTMYLSEAVYLNDSTYDGHTVGGLQYGGLGQLADGVVGLDD
FRKSQELRVWPGYDYVGWSNHSFSSGYVEMEFEFDRLRAFQAMQVHCNNMHTLGARLPGG
VECRFRRGPAMAWEGEPMRHNLGGNLGDPRARAVSVPLGGRVARFLQCRFLFAGPWLLFS
EISFISDVVNNSSPALGGTFPPAPWWPPGPPPTNFSSLELEPRGQQPVAKAEGSPTAILI
GCLVAIILLLLLIIALMLWRLHWRRLLSKAERRVLEEELTVHLSVPGDTILINNRPGPRE
PPPYQEPRPRGNPPHSAPCVPNGSALLLSNPAYRLLLATYARPPRGPGPPTPAWAKPTNT
QAYSGDYMEPEKPGAPLLPPPPQNSVPHYAEADIVTLQGVTGGNTYAVPALPPGAVGDGP
PRVDFPRSRLRFKEKLGEGQFGEVHLCEVDSPQDLVSLDFPLNVRKGHPLLVAVKILRPD
ATKNARNDFLKEVKIMSRLKDPNIIRLLGVCVQDDPLCMITDYMENGDLNQFLSAHQLED
KAAEGAPGDGQAAQGPTISYPMLLHVAAQIASGMRYLATLNFVHRDLATRNCLVGENFTI
KIADFGMSRNLYAGDYYRVQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEVLMLC
RAQPFGQLTDEQVIENAGEFFRDQGRQVYLSRPPACPQGLYELMLRCWSRESEQRPPFSQ
LHRFLAEDALNTV

• ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

• F5_F8_type_C (PF00754 )
• Pkinase_Tyr (PF07714 )

• 1-18

• 417-443

• Membrane
• single-pass type I membrane protein

ATGGGACCAGAGGCCCTGTCATCTTTACTGCTGCTGCTCTTGGTGGCAAGTGGAGATGCT
GACATGAAGGGACATTTTGATCCTGCCAAGTGCCGCTATGCCCTGGGCATGCAGGACCGG
ACCATCCCAGACAGTGACATCTCTGCTTCCAGCTCCTGGTCAGATTCCACTGCCGCCCGC
CACAGCAGGTTGGAGAGCAGTGACGGGGATGGGGCCTGGTGCCCCGCAGGGTCGGTGTTT
CCCAAGGAGGAGGAGTACTTGCAGGTGGATCTACAACGACTGCACCTGGTGGCTCTGGTG
GGCACCCAGGGACGGCATGCCGGGGGCCTGGGCAAGGAGTTCTCCCGGAGCTACCGGCTG
CGTTACTCCCGGGATGGTCGCCGCTGGATGGGCTGGAAGGACCGCTGGGGTCAGGAGGTG
ATCTCAGGCAATGAGGACCCTGAGGGAGTGGTGCTGAAGGACCTTGGGCCCCCCATGGTT
GCCCGACTGGTTCGCTTCTACCCCCGGGCTGACCGGGTCATGAGCGTCTGTCTGCGGGTA
GAGCTCTATGGCTGCCTCTGGAGGGATGGACTCCTGTCTTACACCGCCCCTGTGGGGCAG
ACAATGTATTTATCTGAGGCCGTGTACCTCAACGACTCCACCTATGACGGACATACCGTG
GGCGGACTGCAGTATGGGGGTCTGGGCCAGCTGGCAGATGGTGTGGTGGGGCTGGATGAC
TTTAGGAAGAGTCAGGAGCTGCGGGTCTGGCCAGGCTATGACTATGTGGGATGGAGCAAC
CACAGCTTCTCCAGTGGCTATGTGGAGATGGAGTTTGAGTTTGACCGGCTGAGGGCCTTC
CAGGCTATGCAGGTCCACTGTAACAACATGCACACGCTGGGAGCCCGTCTGCCTGGCGGG
GTGGAATGTCGCTTCCGGCGTGGCCCTGCCATGGCCTGGGAGGGGGAGCCCATGCGCCAC
AACCTAGGGGGCAACCTGGGGGACCCCAGAGCCCGGGCTGTCTCAGTGCCCCTTGGCGGC
CGTGTGGCTCGCTTTCTGCAGTGCCGCTTCCTCTTTGCGGGGCCCTGGTTACTCTTCAGC
GAAATCTCCTTCATCTCTGATGTGGTGAACAATTCCTCTCCGGCACTGGGAGGCACCTTC
CCGCCAGCCCCCTGGTGGCCGCCTGGCCCACCTCCCACCAACTTCAGCAGCTTGGAGCTG
GAGCCCAGAGGCCAGCAGCCCGTGGCCAAGGCCGAGGGGAGCCCGACCGCCATCCTCATC
GGCTGCCTGGTGGCCATCATCCTGCTCCTGCTGCTCATCATTGCCCTCATGCTCTGGCGG
CTGCACTGGCGCAGGCTCCTCAGCAAGGCTGAACGGAGGGTGTTGGAAGAGGAGCTGACG
GTTCACCTCTCTGTCCCTGGGGACACTATCCTCATCAACAACCGCCCAGGTCCTAGAGAG
CCACCCCCGTACCAGGAGCCCCGGCCTCGTGGGAATCCGCCCCACTCCGCTCCCTGTGTC
CCCAATGGCTCTGCGTTGCTGCTCTCCAATCCAGCCTACCGCCTCCTTCTGGCCACTTAC
GCCCGTCCCCCTCGAGGCCCGGGCCCCCCCACACCCGCCTGGGCCAAACCCACCAACACC
CAGGCCTACAGTGGGGACTATATGGAGCCTGAGAAGCCAGGCGCCCCGCTTCTGCCCCCA
CCTCCCCAGAACAGCGTCCCCCATTATGCCGAGGCTGACATTGTTACCCTGCAGGGCGTC
ACCGGGGGCAACACCTATGCTGTGCCTGCACTGCCCCCAGGGGCAGTCGGGGATGGGCCC
CCCAGAGTGGATTTCCCTCGATCTCGACTCCGCTTCAAGGAGAAGCTTGGCGAGGGCCAG
TTTGGGGAGGTGCACCTGTGTGAGGTCGACAGCCCTCAAGATCTGGTTAGTCTTGATTTC
CCCCTTAATGTGCGTAAGGGACACCCTTTGCTGGTAGCTGTCAAGATCTTACGGCCAGAT
GCCACCAAGAATGCCAGGAATGATTTCCTGAAAGAGGTGAAGATCATGTCGAGGCTCAAG
GACCCAAACATCATTCGGCTGCTGGGCGTGTGTGTGCAGGACGACCCCCTCTGCATGATT
ACTGACTACATGGAGAACGGCGACCTCAACCAGTTCCTCAGTGCCCACCAGCTGGAGGAC
AAGGCAGCCGAGGGGGCCCCTGGGGACGGGCAGGCTGCGCAGGGGCCCACCATCAGCTAC
CCAATGCTGCTGCATGTGGCAGCCCAGATCGCCTCCGGCATGCGCTATCTGGCCACACTC
AACTTTGTACATCGGGACCTGGCCACGCGGAACTGCCTAGTTGGGGAAAATTTCACCATC
AAAATCGCAGACTTTGGCATGAGCCGGAACCTCTATGCTGGGGACTATTACCGTGTGCAG
GGCCGGGCAGTGCTGCCCATCCGCTGGATGGCCTGGGAGTGCATCCTCATGGGGAAGTTC
ACGACTGCGAGTGACGTGTGGGCCTTTGGTGTGACCCTGTGGGAGGTGCTGATGCTCTGT
AGGGCCCAGCCCTTTGGGCAGCTCACCGACGAGCAGGTCATCGAGAACGCGGGGGAGTTC
TTCCGGGACCAGGGCCGGCAGGTGTACCTGTCCCGGCCGCCTGCCTGCCCGCAGGGCCTA
TATGAGCTGATGCTTCGGTGCTGGAGCCGGGAGTCTGAGCAGCGACCACCCTTTTCCCAG
CTGCATCGGTTCCTGGCAGAGGATGCACTCAACACGGTGTGA

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