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	CellPhoneDB	No	Yes	Yes	Yes	No
receptor	receptor	GO_Intercell	No	Yes	Yes	Yes	No
receptor	receptor	HPMR	No	Yes	Yes	Yes	No
receptor	receptor	ICELLNET	No	Yes	Yes	Yes	No
receptor	receptor	CellChatDB	No	Yes	Yes	Yes	No
receptor	receptor	CellTalkDB	No	Yes	Yes	Yes	No
receptor	receptor	Surfaceome	No	Yes	Yes	Yes	No
receptor	receptor	Ramilowski2015	No	Yes	Yes	Yes	No
receptor	receptor	Guide2Pharma	No	Yes	Yes	Yes	No
receptor	receptor	LRdb	No	Yes	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	GSK3B	P49841	Yes	Yes	No	Sparser_ProtMapperPhosphoSite_norefSIGNORProtMapperPhosphoSite_ProtMapper	SIGNOR:30711629 ProtMapper:30711629
MET	P08581	RON	Q04912	Yes	No	No	BEL-Large-Corpus_ProtMapperPhosphoSite_norefiPTMnetProtMapperCellinkerPhosphoSitePhosphoSite_ProtMapper	Cellinker:28536399 PhosphoSite:18836480 PhosphoSite:11064459 PhosphoSite:20726546 PhosphoSite:24305878 ProtMapper:10871856 PhosphoSite:10871856 PhosphoSite:24739671 PhosphoSite:20016000
RON	Q04912	MET	P08581	Yes	Yes	No	BEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetProtMapperWangPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:16914575 PhosphoSite:23618918 PhosphoSite:12611639 PhosphoSite:21496277 PhosphoSite:21247903 PhosphoSite:33727228 PhosphoSite:14559966 PhosphoSite:15475459 PhosphoSite:33839159 PhosphoSite:1655790 PhosphoSite:17967179 PhosphoSite:8302603 PhosphoSite:26670562 PhosphoSite:8208547 PhosphoSite:19450681 ProtMapper:10871856 PhosphoSite:16849525 PhosphoSite:12746450 PhosphoSite:21455220
MET	P08581	IRS1	P35568	Yes	No	No	PhosphoSitePhosphoSite_ProtMapperProtMapper	PhosphoSite:34265306 PhosphoSite:7935386 PhosphoSite:15001544 PhosphoSite:20101208 PhosphoSite:17517892 PhosphoSite:12525499 PhosphoSite:20135346 PhosphoSite:34551282 PhosphoSite:15044323 PhosphoSite:22081023 PhosphoSite:11416002 PhosphoSite:17242212 PhosphoSite:14556646 PhosphoSite:33991522
ABL1	P00519	MET	P08581	Yes	Yes	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetProtMapperPhosphoSite_KEAKEAKinexus_KEAWangPhosphoSitePhosphoSite_ProtMapper	KEA:7708691 PhosphoSite:11741535 PhosphoSite:8547236 KEA:10069803 iPTMnet:9826708 KEA:9826708 PhosphoSite:8906793 PhosphoSite:7961992 KEA:9444958 PhosphoSite:12766170 PhosphoSite:7838524 PhosphoSite:12475979 KEA:7513258 PhosphoSite:10490849 KEA:15475459 PhosphoSite:7513258 PhosphoSite:21777671 PhosphoSite:7687741 PhosphoSite:9242692 PhosphoSite:7731718 KEA:7687741 PhosphoSite:10506185 PhosphoSite:9444958 KEA:7731718 KEA:7961992 PhosphoSite:9826708 KEA:8662889 KEA:9252406 PhosphoSite:9391119 KEA:12475979
MET	P08581	RHOA	P61586	Yes	No	No	Sparser_ProtMapperProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:28712859 PhosphoSite:31056743 PhosphoSite:31973815 ProtMapper:31056743 ProtMapper:32392742
MET	P08581	TOPK	Q96KB5	Yes	No	No	PhosphoSitePhosphoSite_ProtMapperProtMapper	PhosphoSite:31611604
KPCE	Q02156	MET	P08581	Yes	No	Yes	BEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointProtMapperPhosphoSite_KEAKEAACSNphosphoELM_KEAphosphoELMWangPhosphoSitePhosphoSite_ProtMapper	ACSN:16488589 ACSN:17496910 ACSN:15567848 KEA:7925482 ProtMapper:15212693 ACSN:12845332 ACSN:14585353 ACSN:12040186 ACSN:19615955 ACSN:11447289 ACSN:11940581 KEA:94124523 ACSN:11313945 ACSN:21386996 ACSN:19568798 KEA:8294430 phosphoELM:15075332 KEA:15075332 ACSN:6321473 ACSN:8321321 PhosphoSite:8294430 PhosphoSite:15075332

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Protein Complex Composition (81)

81 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
ABHD16A HTR3C METTL25 SEC11C	O95870 Q8N6Q8 Q8WXA8 Q9BY50	0:0:0:0	hu.MAP
ALDOA ALDOC GSTO2 HSPA1B ISYNA1 METTL21A NIT1 PDXP	P04075 P09972 P0DMV9 Q86X76 Q8WXB1 Q96GD0 Q9H4Y5 Q9NPH2	0:0:0:0:0:0:0:0	hu.MAP2
INTS6L ISOC2 METTL26 SOD2 UBR2	P04179 Q5JSJ4 Q8IWV8 Q96AB3 Q96S19	0:0:0:0:0	hu.MAP2
MET	P08581	2	PDB	PDB:5lspPDB:4knbPDB:2rfnPDB:3efjPDB:8ouuPDB:7b43PDB:8ovzPDB:9ivbPDB:8aw1PDB:8vi1PDB:3rhkPDB:8ouvPDB:5dg5PDB:8owgPDB:8au3PDB:3efkPDB:5hniPDB:3qtiPDB:6i04PDB:8an8PDB:3f66
CBL MET	P08581 P22681	2:2	PDB	PDB:3bux
CSK EIF2S3 FRK MET PCBP1	P08581 P41091 P41240 P42685 Q15365	0:0:0:0:0	hu.MAP2
FRK MET PCBP1	P08581 P42685 Q15365	0:0:0	hu.MAPhu.MAP2
FRK MET PCBP1 PCBP2	P08581 P42685 Q15365 Q15366	0:0:0:0	hu.MAP2
GRB2 MET	P08581 P62993	4:4	PDB	PDB:1fyr
HKDC1 KYNU METTL1 UBC VCAN WDR4	P0CG48 P13611 P57081 Q16719 Q2TB90 Q9UBP6	1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC8444

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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