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Met (human)

Overview Met a proto-oncogenic receptor tyrosine kinase with high affinity for hepatocyte growth factor. The primary single chain precursor protein is post-translationally cleaved to produce the 45 kDa alpha- and 145 kDa beta-subunits, which are disulfide linked to form the mature receptor. Ligand-binding induces autophosphorylation at multiple tyrosines, which recruit several downstream signaling components, including Gab1, c-Cbl and PI3 kinase. Activating point mutations cause hereditary papillary renal carcinoma. Mutations also seen in sporadic renal cell carcinoma and childhood hepatocellular carcinoma. Upregulation in carcinomas and sarcomas correlates with metastasis and poor outcome. Some gastric carcinomas harbor a translocation that creates an activated TPR-Met fusion protein. A small molecule inhibitor (PHA-665752) shows an effect in gastric carcinoma xenografts. Inhibitors: SU11274, PHA-665752, mAbs. Two alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB. Protein type: EC 2.7.10.1; Protein kinase, TK; Membrane protein, integral; Kinase, protein; Protein kinase, tyrosine (receptor); TK group; Met family Cellular Component: extracellular space; postsynaptic membrane; cell soma; integral to plasma membrane; flagellum; postsynaptic density; cytoplasm; basal plasma membrane; integral to membrane; plasma membrane; excitatory synapse Molecular Function: protein binding; phospholipase binding; protein heterodimerization activity; protein-tyrosine kinase activity; protein complex binding; beta-catenin binding; phosphoinositide 3-kinase binding; hepatocyte growth factor receptor activity; ATP binding Biological Process: lactation; axon guidance; central nervous system neuron differentiation; activation of MAPK activity; protein amino acid autophosphorylation; myoblast proliferation; neuron migration; signal transduction; response to organic cyclic substance; cell surface receptor linked signal transduction; pancreas development; response to wounding; oligodendrocyte development; placenta development; response to drug; positive regulation of mitosis; male gonad development; muscle cell migration; myotube differentiation; cell aging; positive regulation of dendrite morphogenesis; liver development; positive regulation of peptidyl-serine phosphorylation; cell proliferation; sperm motility; branching morphogenesis of a tube; adult behavior; brain development; positive regulation of DNA replication; response to acid Reference #:  P08581 (UniProtKB) Alt. Names/Synonyms: AUTS9; c-Met; Hepatocyte growth factor receptor; HGF receptor; HGF/SF receptor; HGFR; MET; met proto-oncogene (hepatocyte growth factor receptor); met proto-oncogene tyrosine kinase; oncogene MET; Proto-oncogene c-Met; RCCP2; Scatter factor receptor; SF receptor; Tyrosine-protein kinase Met Gene Symbols: MET Molecular weight: 155,541 Da Basal Isoelectric point: 7.02  Predict pI for various phosphorylation states CST Pathways:  Tyrosine Kinases Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below Met 1FYR - I/J/K/L=1356-1359 (human) 1R0P - A=1049-1360 (human) 1R1W - A=1049-1360 (human) 1SHY - B=25-567 (human) 1SSL - A=519-562 (human) 1UX3 - A=25-656 (human) 2G15 - A=1038-1346 (human) 2RFN - A/B=1048-1351 (human) 2RFS - A=1048-1351 (human) 2UZX - B/D=25-741 (human) 2UZY - B/D=25-741 (human) 2WD1 - A=1055-1346 (human) 2WGJ - A=1051-1348 (human) 2WKM - A=1051-1348 (human) 3A4P - A=1049-1360 (human) 3BUX - A/C=997-1009 (human) 3C1X - A=1049-1360 (human) 3CCN - A=1048-1350 (human) 3CD8 - A=1048-1350 (human) 3CE3 - A=1049-1360 (human) 3CTH - A=1049-1360 (human) 3CTJ - A=1049-1360 (human) 3DKC - A=1049-1360 (human) 3DKF - A=1049-1360 (human) 3DKG - A=1049-1360 (human) 3EFJ - A/B=1048-1351 (human) 3EFK - A/B=1048-1351 (human) 3F66 - A/B=1052-1349 (human) 3F82 - A=1049-1360 (human) 3I5N - A=1048-1350 (human) 3L8V - A=1049-1360 (human) 3LQ8 - A=1051-1348 (human) 3Q6U - A=1048-1348 (human) 3Q6W - A=1048-1348 (human) 3QTI - A/B=1050-1360 (human) 3R7O - A=1048-1348 (human) 3RHK - A/B=1038-1346 (human) 3U6H - A=1048-1351 (human) 3U6I - A=1048-1351 (human) 3ZXZ - A=1051-1348 (human) 3ZZE - A=1051-1348 (human) 4AOI - A=1051-1348 (human) 4AP7 - A=1051-1348 (human) 4DEG - A=1048-1351 (human) 4DEH - A=1048-1351 (human) 4DEI - A=1048-1351 (human) 4EEV - A=1038-1346 (human) 4GG5 - A=1038-1346 (human) 4GG7 - A=1038-1346 (human) Substrate Sequence Logo

STRING  |  Scansite  |  KinBase  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1FYR 1R0P 1R1W 1SHY 1SSL 1UX3 2G15 2RFN 2RFS 2UZX 2UZY 2WD1 2WGJ 2WKM 3A4P 3BUX 3C1X 3CCN 3CD8 3CE3 3CTH 3CTJ 3DKC 3DKF 3DKG 3EFJ 3EFK 3F66 3F82 3I5N 3L8V 3LQ8 3Q6U 3Q6W 3QTI 3R7O 3RHK 3U6H 3U6I 3ZXZ 3ZZE 4AOI 4AP7 4DEG 4DEH 4DEI 4EEV 4GG5 4GG7  |  ENZYME  |  Phospho3D  |  DISEASE 114550 164860 605074 611015  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene

	Sites Implicated In
cell growth, altered: Y1003‑p, Y1234‑p, Y1235‑p, Y1349‑p, Y1356‑p cell motility, altered: Y1234‑p, Y1235‑p, Y1349‑p, Y1356‑p activation: Y1003‑p, Y1234‑p, Y1235‑p enzymatic activity, induced: Y1003‑p, Y1234‑p, Y1235‑p enzymatic activity, inhibited: S985‑p, Y1349‑p, Y1356‑p inhibition: Y1349‑p, Y1356‑p molecular association, regulation: Y1003‑p, Y1349‑p, Y1356‑p phosphorylation: Y1234‑p, Y1235‑p protein conformation: Y1234‑p, Y1235‑p protein degradation: Y1003‑p protein stabilization: Y1003‑p receptor desensitization, altered: Y1003‑p ubiquitination: Y1003‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		T17-p	GILVLLFtLVQRSNG
0	1		K189-u	AKVLSSVkDRFINFF
0	1		K223-u	VRRLKETkDGFMFLT
0	1		S283	TRIIRFCSINSGLHS
0	1		K324-u	LQAAYVSkPGAQLAR
0	1		T474	VSRSGPSTPHVNFLL
0	1		S637-p	MNKHFNMsIIIsNGH
0	1		S641-p	FNMsIIIsNGHGTTQ
0	1		K765-u	STITGVGkNLNSVSV
1	0		Y830-p	LDGILSKyFDLIYVH
0	2		K962-u	LKKRKQIkDLGsELV
0	2		S966-p	KQIkDLGsELVRyDA
0	3		Y971-p	LGsELVRyDARVHtP
0	4		T977-p	RyDARVHtPHLDRLV
4	0		S985-p	PHLDRLVsARsVsPt
0	14		S988-p	DRLVsARsVsPttEM
0	26		S990-p	LVsARsVsPttEMVs
0	11		T992-p	sARsVsPttEMVsNE
0	6		T993-p	ARsVsPttEMVsNEs
0	17		S997-p	sPttEMVsNEsVDyR
1	39		S1000-p	tEMVsNEsVDyRAtF
9	327		Y1003-p	VsNEsVDyRAtFPED
0	9		T1006-p	EsVDyRAtFPEDQFP
0	2		S1016-p	EDQFPNSsQNGsCRQ
0	1		S1020-p	PNSsQNGsCRQVQyP
0	15		Y1026-p	GsCRQVQyPLTDMSP
0	29		Y1093-p	RGHFGCVyHGtLLDN
0	3		T1096-p	FGCVyHGtLLDNDGK
0	3		K1104-u	LLDNDGKkIHCAVKS
0	3		Y1159-p	SPLVVLPyMkHGDLR
0	1		K1161-u	LVVLPyMkHGDLRNF
0	1		K1190-a	GFGLQVAkGMkyLAS
0	3		K1190-u	GFGLQVAkGMkyLAS
0	1		K1193-u	LQVAkGMkyLASKKF
0	2		Y1194-p	QVAkGMkyLASKKFV
0	1		R1227	VADFGLARDMyDkEy
4	106		Y1230-p	FGLARDMyDkEyysV
0	1		K1232-u	LARDMyDkEyysVHN
32	714		Y1234-p	RDMyDkEyysVHNkt
33	416		Y1235-p	DMyDkEyysVHNktG
0	167		S1236-p	MyDkEyysVHNktGA
0	1		K1240-u	EyysVHNktGAKLPV
0	5		T1241-p	yysVHNktGAKLPVK
0	1		K1259	LESLQTQKFTTKSDV
0	4		T1289-p	PPYPDVNtFDITVYL
0	2		Y1307-p	RRLLQPEyCPDPLyE
4	5		Y1313-p	EyCPDPLyEVMLkCW
0	2		K1318-u	PLyEVMLkCWHPKAE
0	2		S1342-p	SRISAIFstFIGEHy
0	6		T1343-p	RISAIFstFIGEHyV
22	94		Y1349-p	stFIGEHyVHVNAty
0	35		T1355-p	HyVHVNAtyVNVKCV
22	93		Y1356-p	yVHVNAtyVNVKCVA
6	94		Y1365-p	NVKCVAPyPsLLssE
0	6		S1367-p	KCVAPyPsLLssEDN
0	2		S1370-p	APyPsLLssEDNADD
0	1		S1371-p	PyPsLLssEDNADDE

	mouse
S17	GILVLLLSLVQRSHG
K188	AKVLLSEKDRFINFF
Q222	VRRLKETQDGFKFLT
S282-p	TRIIRFCsVDSGLHS
K323	LQAAYVSKPGANLAK
T473-p	LSRTAHLtPHVNFLL
S636	MSEHFNVSVIISNSR
S640	FNVSVIISNSRETTQ
K764	STITGIGKTLNSVSL
H829	LDGILSKHFDLTYVH
K960	WMRKRKHKDLGSELV
S964	RKHKDLGSELVRYDA
Y969	LGSELVRYDARVHTP
T975	RYDARVHTPHLDRLV
S983-p	PHLDRLVsARSVSPT
S986	DRLVsARSVSPTTEM
S988	LVsARSVSPTTEMVs
T990	sARSVSPTTEMVsNE
T991	ARSVSPTTEMVsNEs
S995-p	SPTTEMVsNEsVDyR
S998-p	TEMVsNEsVDyRATF
Y1001-p	VsNEsVDyRATFPED
T1004	EsVDyRATFPEDQFP
S1014	EDQFPNSSQNGACRQ
A1018	PNSSQNGACRQVQYP
Y1024	GACRQVQYPLTDLSP
Y1091	RGHFGCVYHGTLLDN
T1094	FGCVYHGTLLDNDGK
K1102	LLDNDGKKIHCAVKS
Y1157	SPLVVLPYMKHGDLR
K1159	LVVLPYMKHGDLRNF
K1188	GFGLQVAKGMKyLAS
K1188	GFGLQVAKGMKyLAS
K1191	LQVAKGMKyLASKKF
Y1192-p	QVAKGMKyLASKKFV
R1225-m1	VADFGLArDMyDKEy
Y1228-p	FGLArDMyDKEyysV
K1230	LArDMyDKEyysVHN
Y1232-p	rDMyDKEyysVHNKt
Y1233-p	DMyDKEyysVHNKtG
S1234-p	MyDKEyysVHNKtGA
K1238	EyysVHNKtGAKLPV
T1239-p	yysVHNKtGAKLPVK
K1257-u	LESLQTQkFTTKSDV
T1287	PPYPDVNTFDITIYL
Y1305	RRLLQPEYCPDALyE
Y1311-p	EYCPDALyEVMLKCW
K1316	ALyEVMLKCWHPKAE
S1340	SRISSIFSTFIGEHy
T1341	RISSIFSTFIGEHyV
Y1347-p	STFIGEHyVHVNATy
T1353	HyVHVNATyVNVKCV
Y1354-p	yVHVNATyVNVKCVA
Y1363-p	NVKCVAPyPSLLPSQ
S1365	KCVAPyPSLLPSQDN
P1368	APyPSLLPSQDNIDG
S1369	PyPSLLPSQDNIDGE

	rat
T17	GILLLLLTLAQRSHG
K190	AKVLLSEKDRFINFF
Q224	VRRLKETQDGFKFLT
S284	TRIIRFCSVDSGLHS
K325	LQAAYVSKPGANLAK
T475	LSRTAHFTPHVNFLL
S638	MSEHFNVSVIVSNSR
S642	FNVSVIVSNSRETTQ
K766	STITGIGKNLNSVST
H831	LDGILSKHFDLTYVH
K963	WLRKRKHKDLGSELV
S967	RKHKDLGSELVRYDA
Y972	LGSELVRYDARVHTP
T978	RYDARVHTPHLDRLV
S986-p	PHLDRLVsARSVSPT
S989	DRLVsARSVSPTTEM
S991	LVsARSVSPTTEMVS
T993	sARSVSPTTEMVSNE
T994	ARSVSPTTEMVSNES
S998	SPTTEMVSNESVDYR
S1001	TEMVSNESVDYRATF
Y1004	VSNESVDYRATFPED
T1007	ESVDYRATFPEDQFP
S1017	EDQFPNSSQNGACRQ
A1021	PNSSQNGACRQVQYL
Y1027	GACRQVQYLLTDLSP
Y1094	RGHFGCVYHGTLLDS
T1097	FGCVYHGTLLDSDGK
K1105	LLDSDGKKIHCAVKS
Y1160	SPLVVLPYMKHGDLR
K1162	LVVLPYMKHGDLRNF
K1191	GFGLQVAKGMKYLVS
K1191	GFGLQVAKGMKYLVS
K1194	LQVAKGMKYLVSKKF
Y1195	QVAKGMKYLVSKKFV
R1228	VADFGLARDMYDKEy
Y1231	FGLARDMYDKEyySV
K1233	LARDMYDKEyySVHN
Y1235-p	RDMYDKEyySVHNKT
Y1236-p	DMYDKEyySVHNKTG
S1237	MYDKEyySVHNKTGA
K1241	EyySVHNKTGAKLPV
T1242	yySVHNKTGAKLPVK
K1260	LESLQTQKFTTKSDV
T1290	PPYPDVNTFDITIYL
Y1308	RRLLQPEYCPDALYE
Y1314	EYCPDALYEVMLKCW
K1319	ALYEVMLKCWHPKAE
S1343	SRISSIFSTFIGEHY
T1344	RISSIFSTFIGEHYV
Y1350	STFIGEHYVHVNATY
T1356	HYVHVNATYVNVKCV
Y1357	YVHVNATYVNVKCVA
Y1366	NVKCVAPYPSLLPSQ
S1368	KCVAPYPSLLPSQDN
P1371	APYPSLLPSQDNIDG
S1372	PYPSLLPSQDNIDGE

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