Protein detail

MET

Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)

Entry name MET	UniProt ID P08581	EVMP confidence score 0.40
Supporting publications (n) 3	Transmembrane count 1	Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteinsTransporters

Basic Information

Protein Names

Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)

Protein Class (11)

Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteinsTransporters

Protein Function (17)

Human disease related genes:Cancers:Cancers of the lung and pleura
Human disease related genes:Cancers:Cancers of the digestive system
Human disease related genes:Nervous system diseases:Ear disease
Predicted intracellular proteins
ENZYME proteins:Transferases
Cancer-related genes:Mutated cancer genes
Human disease related genes:Cancers:Cancers of soft tissues and bone
RAS pathway related proteins
Enzymes
Cancer-related genes:Candidate cancer biomarkers

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Transmembrane

933..955; Helical

Transmembrane Count

Ensembl

ENSG00000105976

Entrez Gene Symbol

MET

Gene Synonym (3)

DFNB97HGFRRCCP2

Gene Description

MET proto-oncogene, receptor tyrosine kinase

Chromosome

Position

116672196-116798377

Supporting publications (n)

EVMP confidence score

0.40

Fluorescence & Localization

Tissue SpecificintestineBrain Regional Specificbasal gangliaCell SpecificAdipocytesSingle-Nuclei Brain Specificlower rhombic lipBlood Cell SpecificneutrophilBlood Lineage Specificgranulocytes

Function & Pathway

Protein Function (17)

Human disease related genes:Cancers:Cancers of the lung and pleura
Human disease related genes:Cancers:Cancers of the digestive system
Human disease related genes:Nervous system diseases:Ear disease
Predicted intracellular proteins
ENZYME proteins:Transferases
Cancer-related genes:Mutated cancer genes
Human disease related genes:Cancers:Cancers of soft tissues and bone
RAS pathway related proteins
Enzymes
Cancer-related genes:Candidate cancer biomarkers

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Cellular Component (7)

Molecular Function (8)

Biological Process (3)

KEGG (25)

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Reactome (33)

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Mediation Categories (4)

Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation

Relations & Evidence242

Enzyme-Mediated Modification (71)

71 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
MET	PTPRG	P23470	Y	1,003	dephosphorylation	SIGNOR	SIGNOR:25624455
MET	PTPRG	P23470	Y	1,003	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:25624455
MET	PTPRJ	Q12913	Y	1,365	dephosphorylation	SIGNORDEPOD	SIGNOR:12475979 DEPOD:12475979
MET	PTPRJ	Q12913	Y	1,349	dephosphorylation	HPRDSIGNORDEPOD	HPRD:12370829 SIGNOR:12475979 DEPOD:12475979
MET	PTPRJ	Q12913	Y	1,356	dephosphorylation	HPRD	HPRD:12370829
MET	PTPRJ	Q12913	Y	1,356	phosphorylation	NCI-PID_ProtMapperProtMapper	ProtMapper:12475979
MET	PTPRJ	Q12913	Y	1,349	phosphorylation	NCI-PID_ProtMapperProtMapperReactome_ProtMapperKEASIGNOR_ProtMapper	ProtMapper:12475979 KEA:15475459
MET	PTPRJ	Q12913	Y	1,003	phosphorylation	NCI-PID_ProtMapperProtMapper	ProtMapper:12475979
MET	PTPRJ	Q12913	Y	1,365	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:12475979
MET	PRKCA	P17252	S	985	phosphorylation	SIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	SIGNOR:8294430 KEA:8294430 KEA:15075332 ProtMapper:8294430 KEA:17570479 KEA:94124523

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Ligand-Receptor Signaling (61)

61 records.

Category	Parent	Database	Receiver	Secreted	Plasma Membrane (Transmembrane)
receptor	receptor	CellPhoneDB	Yes	Yes	Yes
receptor	receptor	GO_Intercell	Yes	Yes	Yes
receptor	receptor	HPMR	Yes	Yes	Yes
receptor	receptor	ICELLNET	Yes	Yes	Yes
receptor	receptor	CellChatDB	Yes	Yes	Yes
receptor	receptor	CellTalkDB	Yes	Yes	Yes
receptor	receptor	Surfaceome	Yes	Yes	Yes
receptor	receptor	Ramilowski2015	Yes	Yes	Yes
receptor	receptor	Guide2Pharma	Yes	Yes	Yes
receptor	receptor	LRdb	Yes	Yes	Yes

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Regulatory Interaction Network (28)

28 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
MET	P08581	FAK1	Q05397	Yes	Yes		WangphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperKEAKinexus_KEALi2012SIGNOR_ProtMapperREACH_ProtMapperPhosphoSite_ProtMapper	ProtMapper:22188814 ProtMapper:20802513 SIGNOR:16782899 SIGNOR:20802513 KEA:15611085 KEA:15561106 KEA:15247219 ProtMapper:16782899 ProtMapper:30134553 KEA:14572662 KEA:15598735
MET	P08581	PARP1	P09874	Yes	Yes		Sparser_ProtMapperiPTMnetSIGNORProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:32563252 ProtMapper:33015624 ProtMapper:28255272 SIGNOR:26779812 ProtMapper:32180937 ProtMapper:30573522 ProtMapper:29805738 ProtMapper:32201536 PhosphoSite:26779812 ProtMapper:32405340 ProtMapper:26779812 PhosphoSite:31399520 ProtMapper:31835379 ProtMapper:33520371
PTN2	P17706	MET	P08581	Yes		Yes	WangNCI-PID_ProtMapperSIGNORProtMapperDEPODReactome_ProtMapperSIGNOR_ProtMapper	SIGNOR:18819921 DEPOD:18819921 ProtMapper:18819921
MET	P08581	GRB2	P62993	Yes	Yes		KEGG-MEDICUSPhosphoPointSIGNORLi2012HPRDELMCui2007HINTBioGRIDLMPIDWang	HINT:7511210 HINT:9660480 LMPID:12475979 ELM:11063574 ELM:12475979 HPRD:11439336 HPRD:9660480 LMPID:11063574 HINT:8662889 HPRD:8662889 HINT:15546961 HINT:21222362 BioGRID:8662889 HPRD:7511210 HPRD:15546961 SIGNOR:22128289 HINT:11063574 HINT:11439336
MECP2	P51608	MET	P08581	Yes		Yes	SIGNOR	SIGNOR:24150225
PTPRG	P23470	MET	P08581	Yes		Yes	SIGNOR_ProtMapperSIGNORProtMapper	SIGNOR:25624455 ProtMapper:25624455
KPCA	P17252	MET	P08581	Yes		Yes	WangphosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_ProtMapperHPRD_MIMPiPTMnetSIGNORProtMapperPhosphoSite_KEAKEAACSNKinexus_KEASIGNOR_ProtMapperNetworKIN_KEA	ACSN:16488589 ACSN:17496910 ACSN:15567848 SIGNOR:8294430 ACSN:12845332 ACSN:14585353 ACSN:12040186 ACSN:19615955 ACSN:11447289 ACSN:11940581 KEA:94124523 ACSN:11313945 ACSN:21386996 ACSN:19568798 KEA:8294430 KEA:15075332 ACSN:6321473 ProtMapper:8294430 KEA:17570479 ACSN:8321321
UBP8	P40818	MET	P08581	Yes		Yes	SIGNOR	SIGNOR:16520378
PTPRB	P23467	MET	P08581	Yes		Yes	SIGNORProtMapperDEPODHPRDSIGNOR_ProtMapper	ProtMapper:21454675 HPRD:16101282 ProtMapper:16101282 DEPOD:21454675 SIGNOR:16101282 SIGNOR:21454675
MET	P08581	IQGA1	P46940	Yes	Yes		SIGNORPhosphoSitePhosphoSite_ProtMapperProtMapper	SIGNOR:33087447 PhosphoSite:33087447

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Protein Complex Composition (81)

81 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
METTL2A METTL2B	Q6P1Q9 Q96IZ6	0:0	hu.MAP2
LRRC56 METAP1D	Q6UB28 Q8IYG6	0:0	hu.MAP2
LRRC56 METAP1D XAGE3	Q6UB28 Q8IYG6 Q8WTP9	0:0:0	hu.MAP2
CPEB1 LRRC56 METAP1D	Q6UB28 Q8IYG6 Q9BZB8	0:0:0	hu.MAP2
LRRC56 METAP1D RANGRF	Q6UB28 Q8IYG6 Q9HD47	0:0:0	hu.MAP2
METTL9 SLC39A5	Q6ZMH5 Q9H1A3	2:2	PDB	PDB:7yf2PDB:7yf4PDB:7y9c
METTL14 METTL3 RBM15B	Q86U44 Q8NDT2 Q9HCE5	0:0:0	hu.MAPhu.MAP2
METTL14 METTL3 SNF8 SNX15	Q86U44 Q96H20 Q9HCE5 Q9NRS6	0:0:0:0	Havugimana2012	Havugimana2012:C_266
METTL16	Q86W50	3	PDB	PDB:6gfkPDB:2h00PDB:6gt5
FKRP METTL16 SLC39A9	Q86W50 Q9H9S5 Q9NUM3	0:0:0	hu.MAP2

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Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometry	6	38113368 37322475 40189497 36146834 31805958 38207106

Sequence, Structure & Domains

Sequences

Length

1,390

Mass

155,541

Sequence

MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVDTRPASFWETS

Alternative Products

Event=Alternative splicing; Named isoforms=3; Comment=Additional soluble isoforms seem to exist.; Name=1; IsoId=P08581-1; Sequence=Displayed; Name=2; IsoId=P08581-2; Sequence=VSP_005005; Name=3; Synonyms=Soluble MET variant 4; IsoId=P08581-3; Sequence=VSP_042447, VSP_042448

Alternative Sequence

755..764; SGGSTITGVG -> RHVNIALIQR (in isoform 3); 755; S -> STWWKEPLNIVSFLFCFAS (in isoform 2); 765..1390; Missing (in isoform 3)

3D Structural Models

Turn

75..77; 242..244; 395..397; 429..436; 496..498; 1172..1174; 1227..1230; 1239..1241; 1354..1358

Helix

25..30; 103..105; 205..208; 231..233; 239..241; 327..333; 367..374; 380..382; 387..390; 520..522; 526..529; 534..536; 548..550; 614..616; 1048..1050; 1055..1057; 1060..1066; 1067..1069; 1073..1075; 1118..1132; 1165..1170; 1178..1197; 1207..1209; 1224..1226; 1232..1234; 1247..1249; 1252..1257; 1262..1277; 1289..1291; 1292..1297; 1310..1319; 1324..1326; 1330..1342

Beta Strand

45..47; 52..58; 61..66; 69..74; 80..84; 89..91; 93..95; 97..99; 111..113; 119..123; 125..133; 135..139; 141..145; 155..160; 166..168; 173..175; 182..189; 192..199; 213..219; 247..255; 258..268; 272..274; 277..281; 284..286; 292..300; 312..314; 316..323; 341..349; 356..366; 383..385; 392..394; 418..422; 424..427; 439..447; 450..457; 462..466; 469..471; 476..480; 490..493; 501..506; 509..514; 539..541; 544..546; 552..554; 557..559; 564..574; 580..586; 589..592; 595..598; 602..605; 619..625; 633..641; 646..655; 658..663; 665..668; 674..681; 688..692; 698..702; 704..710; 718..726; 729..739; 1076..1087; 1090..1098; 1100..1102; 1104..1111; 1144..1146; 1149..1151; 1154..1158; 1161..1163; 1210..1212; 1218..1220; 1235..1237; 1244..1246; 1283..1287

3D Structure

Electron microscopy (5); NMR spectroscopy (1); X-ray crystallography (114)

Domain & Motif Annotations

Domain (CC)

The kinase domain is involved in SPSB1 binding.; DOMAIN: The beta-propeller Sema domain mediates binding to HGF.

Domain (FT)

27..515; Sema; 563..655; IPT/TIG 1; 657..739; IPT/TIG 2; 742..836; IPT/TIG 3; 1078..1345; Protein kinase

Region

1212..1390; Interaction with RANBP9; 1320..1359; Interaction with MUC20

Protein Families (2)

Protein kinase superfamily
Tyr protein kinase family

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Clinical Relevance

Disease Involvement (6)

Cancer-related genesDeafnessDisease variantFDA approved drug targetsNon-syndromic deafnessProto-oncogene

Biomarker

Phase 1/2; Phase 2; Phase 1; Phase 3; Discontinued in Phase 2; Approved; Preclinical

Drug Targets

FDA approved drug targets

Drugs (101)

FORETINIB GEFITINIB SELUMETINIB TIVANTINIB TEPOTINIB CABOZANTINIB S-MALATE OSIMERTINIB GLESATINIB ANTI-MET MONOCLONAL ANTIBODY MIXTURE SYM015 CAPMATINIB CETUXIMAB ROCILETINIB EMIBETUZUMAB CHEMBL:CHEMBL546797 BMS-754807 BMS-777607 NULL CEP-11981 -SAR 125844.00 DACTOLISIB TEREVALEFIM AMG-208 PEMBROLIZUMAB EUCALYPTIN A MACROCARPAL B MET TYROSINE KINASE INHIBITOR SGX523 MITOGEN-ACTIVATED PROTEIN KINASE KINASE INHIBITOR BMS-794833 PF-04217903 SAVOLITINIB TRAMETINIB DIMETHYL SULFOXIDE OLEOCANTHAL EMB-01 TAS-115 VEMURAFENIB TELISOTUZUMAB ZM447439 C-MET INHIBITOR AMG 208 CRIZOTINIB CAPMATINIB HYDROCHLORIDE SITRAVATINIB MK-8033 MK-2461 GALLOCATECHIN GALLATE EMD-1204831 TELISOTUZUMAB VEDOTIN PF-562271 TEPOTINIB HYDROCHLORIDE BMS-698769 ALTIRATINIB NVP-TAE684 ONARTUZUMAB EPIGALLOCATECHIN-3-GALLATE CMX-2043 PD-0166285 SP-600125 YUANHUADINE LAPATINIB SU11274 BMS-817378 AMG-337 PAZOPANIB MERESTINIB PHA-665752 PALBOCICLIB CP-547632 ERLOTINIB SGX-523 JNJ-38877605 AMUVATINIB ANTI-C-MET MONOCLONAL ANTIBODY SAIT301 CHEMBL:CHEMBL1997335 MACROCARPAL A GOLVATINIB ENTRECTINIB BEPERMINOGENE PERPLASMID ANTI-MET/EGFR MONOCLONAL ANTIBODY LY3164530 TAMATINIB CHEMBL:CHEMBL399530 CRENOLANIB RITUXIMAB SNS-314 C-MET INHIBITOR MK2461 C-MET INHIBITOR AMG 337 PANITUMUMAB C-MET INHIBITOR ARRY-300 BPI-9016 ILORASERTIB TYROSOL SINAPATE CENISERTIB CYC-116 EPICATECHIN GALLATE NINGETINIB APRATOXIN F AMIVANTAMAB-VMJW LINIFANIB ANTI-EGFR MONOCLONAL ANTIBODY VEBRELTINIB BAY 61-3606 JNJ-7706621

Antibody (2)

CAB005282 HPA055607

Interaction Protein (6)

ENSG00000010017ENSG00000019991ENSG00000103423ENSG00000110395ENSG00000146648ENSG00000197122

Interaction Count

Interaction Dataset

intact_biogrid

Supporting Publications3

PMID	Title	Related sentences
29889559	Higher exosomal phosphorylated tau and total tau among veterans with combat-related repetitive chronic mild traumatic brain injury.	Tau, p-tau, Aβ40, and Aβ42 were measured by ultrasensitive immunoassay in plasma and exosomes from 195 Veterans enrolled in the Chronic Effects of Neurotrauma Consortium Multicenter Observational Study.
37673813	Assessment of Risk Factors for Postoperative Delirium in Older Adults Who Underwent Spinal Surgery and Identifying Associated Biomarkers Using Exosomal Protein.	To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology.
38257772	CSF Extracellular Vesicle Aβ42 and Tau/Aβ42 Ratio Are Associated with Cognitive Impairment in Older People with HIV.	Given the role of extracellular vesicles (EVs) in age-related neurological disorders, we investigated soluble and EV-associated Aβ42, total Tau, NFL, GFAP, ICAM-1, VCAM-1, and CRP in relation to cognitive impairment in PWH.