EV MemProt Atlas

Basic Information13

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

1

Ensembl

ENSG00000105976

Entrez Gene Symbol

MET

Gene Synonym (3)

DFNB97HGFRRCCP2

Gene Description

MET proto-oncogene, receptor tyrosine kinase

Chromosome

7

Position

116672196-116798377

Supporting publications (n)

3

EVMP confidence score

0.38

Fluorescence & Localization7

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

Function & Pathway7

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	PRKCD	Q05655	S	985	phosphorylation	ProtMapperKEAphosphoELMPhosphoSitePhosphoSite_ProtMapper	KEA:7925482 KEA:8294430 phosphoELM:15075332 KEA:15075332 KEA:94124523
MET	PRKCD	Q05655	S	1,003	phosphorylation	MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP
MET	PRKCE	Q02156	S	985	phosphorylation	BEL-Large-Corpus_ProtMapperProtMapperKEAphosphoELMPhosphoSitePhosphoSite_ProtMapper	KEA:7925482 ProtMapper:15212693 KEA:8294430 phosphoELM:15075332 KEA:15075332 KEA:94124523
MET	PRKCE	Q02156	S	1,003	phosphorylation	MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP
MET	PTPN2	P17706	Y	1,235	dephosphorylation	SIGNORDEPOD	SIGNOR:18819921 DEPOD:18819921
MET	PTPN2	P17706	Y	1,234	dephosphorylation	SIGNORDEPOD	SIGNOR:18819921 DEPOD:18819921
MET	PTPN2	P17706	Y	1,356	phosphorylation	NCI-PID_ProtMapperProtMapper	ProtMapper:18819921
MET	PTPN2	P17706	Y	1,234	phosphorylation	NCI-PID_ProtMapperSIGNOR_ProtMapperReactome_ProtMapperProtMapper	ProtMapper:18819921
MET	PTPN2	P17706	Y	1,349	phosphorylation	NCI-PID_ProtMapperProtMapper	ProtMapper:18819921
MET	PTPN2	P17706	Y	1,235	phosphorylation	NCI-PID_ProtMapperSIGNOR_ProtMapperReactome_ProtMapperProtMapper	ProtMapper:18819921

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Ligand-Receptor Signaling (61)

61 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	SignaLink_function	No	Yes	Yes	Yes	No
kinase	receptor	Almen2009	No	Yes	Yes	Yes	No
kinase	receptor	Surfaceome	No	Yes	Yes	Yes	No
growth_factor	receptor	ICELLNET	No	Yes	Yes	Yes	No
semaphorin	receptor	ICELLNET	No	Yes	Yes	Yes	No
receptor	receptor	OmniPath	No	Yes	Yes	Yes	No
extracellular	extracellular	HPMR	No	No	Yes	Yes	No
extracellular	extracellular	OmniPath	No	No	Yes	Yes	No
intracellular	intracellular	ComPPI	No	No	Yes	Yes	No
intracellular	intracellular	GO_Intercell	No	No	Yes	Yes	No

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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	No	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	No	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	No	Yes	WangNCI-PID_ProtMapperSIGNORProtMapperDEPODReactome_ProtMapperSIGNOR_ProtMapper	SIGNOR:18819921 DEPOD:18819921 ProtMapper:18819921
MET	P08581	GRB2	P62993	Yes	Yes	No	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	No	Yes	SIGNOR	SIGNOR:24150225
PTPRG	P23470	MET	P08581	Yes	No	Yes	SIGNOR_ProtMapperSIGNORProtMapper	SIGNOR:25624455 ProtMapper:25624455
KPCA	P17252	MET	P08581	Yes	No	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	No	Yes	SIGNOR	SIGNOR:16520378
PTPRB	P23467	MET	P08581	Yes	No	Yes	SIGNORProtMapperDEPODHPRDSIGNOR_ProtMapper	ProtMapper:21454675 HPRD:16101282 ProtMapper:16101282 DEPOD:21454675 SIGNOR:16101282 SIGNOR:21454675
MET	P08581	IQGA1	P46940	Yes	Yes	No	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
CDK17 KYNU METTL1 PRKACG UBC WDR4	P0CG48 P22612 P57081 Q00537 Q16719 Q9UBP6	1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC5525
HKDC1 HSPA13 KYNU METTL1 UBC WDR4	P0CG48 P48723 P57081 Q16719 Q2TB90 Q9UBP6	1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC9838
CNBP HSPA8 METTL21A PRKDC YARS1	P11142 P54577 P62633 P78527 Q8WXB1	0:0:0:0:0	hu.MAP2
BTF3 METAP1 NAA10 NAA15 NACA Q6IBH6 RPL19 RPL22 RPL23A RPL28 RPL35 RPL38 RPL4 RPL6	P20290 P35268 P36578 P41227 P42766 P46779 P53582 P62750 P63173 P84098 Q02878 Q13765 Q6IBH6 Q9BXJ9	1:1:1:1:1:1:1:1:1:1:1:1:1:1	PDB	PDB:9fq0
METTL13 SAE1 SUMO2 UBA2 UBE2I USP8	P40818 P61956 P63279 Q8N6R0 Q9UBE0 Q9UBT2	0:0:0:0:0:0	hu.MAP2
ID4 METTL2A METTL2B	P47928 Q6P1Q9 Q96IZ6	0:0:0	hu.MAP2
DIS3L2 GCLC METTL13 SAE1 SUMO3	P48506 P55854 Q8IYB7 Q8N6R0 Q9UBE0	0:0:0:0:0	hu.MAP2
AAAS GCLC METTL13 NDC1 PYROXD2 SAE1 SUMO2 UBA2 UBE2I ZNF451	P48506 P61956 P63279 Q8N2H3 Q8N6R0 Q9BTX1 Q9NRG9 Q9UBE0 Q9UBT2 Q9Y4E5	0:0:0:0:0:0:0:0:0:0	hu.MAP2
GCLC METTL13 SAE1	P48506 Q8N6R0 Q9UBE0	0:0:0	hu.MAP2
METTL6 SARS1	P49591 Q8TCB7	2:1	PDB	PDB:8p7dPDB:8p7cPDB:8p7b

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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 & Domains14

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 Relevance9

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

6

Interaction Dataset

intact_biogrid

Supporting Publications3

PMID	Title	Abstract
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.

Entry name MET	UniProt ID P08581	EVMP confidence score 0.38
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