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 | 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 |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic 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
Entrez Gene Symbol
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)
- GO:0004713 protein tyrosine kinase activity
- GO:0005008 hepatocyte growth factor receptor activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0017154 semaphorin receptor activity
- GO:0019903 protein phosphatase binding
- GO:0042802 identical protein binding
- GO:0140677 molecular function activator activity
Biological Process (3)
KEGG (25)
- hsa01521 EGFR tyrosine kinase inhibitor resistance
- KEGG:hsa04010 MAPK signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04360 Axon guidance
- KEGG:hsa04510 Focal adhesion
- KEGG:hsa04518 Integrin signaling
- KEGG:hsa04519 Cadherin signaling
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Reactome (33)
- R-hsa-9824439 bacterial infection pathways
- R-hsa-2219530 constitutive signaling by aberrant pi3k in cancer
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-5663205 infectious disease
- R-hsa-8875360 inlb mediated entry of listeria monocytogenes into host cell
- R-hsa-9006925 intracellular signaling by second messengers
- R-hsa-8876384 listeria monocytogenes entry into host cells
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-9022699 mecp2 regulates neuronal receptors and channels
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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:7925482KEA:8294430phosphoELM:15075332KEA:15075332KEA:94124523 |
| MET | PRKCD | Q05655 | S | 1,003 | phosphorylation | MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP | |
| MET | PRKCE | Q02156 | S | 985 | phosphorylation | BEL-Large-Corpus_ProtMapperProtMapperKEAphosphoELMPhosphoSitePhosphoSite_ProtMapper | KEA:7925482ProtMapper:15212693KEA:8294430phosphoELM:15075332KEA:15075332KEA:94124523 |
| MET | PRKCE | Q02156 | S | 1,003 | phosphorylation | MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP | |
| MET | PTPN2 | P17706 | Y | 1,235 | dephosphorylation | SIGNORDEPOD | SIGNOR:18819921DEPOD:18819921 |
| MET | PTPN2 | P17706 | Y | 1,234 | dephosphorylation | SIGNORDEPOD | SIGNOR:18819921DEPOD: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) |
|---|---|---|---|---|---|---|---|
| intracellular | intracellular | OmniPath | No | No | Yes | Yes | No |
| cell_adhesion | cell_adhesion | Cellinker | Yes | Yes | Yes | Yes | No |
| adhesion | adhesion | OmniPath | Yes | Yes | Yes | Yes | No |
| cell_adhesion | cell_adhesion | OmniPath | Yes | Yes | Yes | Yes | No |
| transmembrane | transmembrane | UniProt_location | No | No | Yes | Yes | No |
| transmembrane | transmembrane | UniProt_topology | No | No | Yes | Yes | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | Yes | Yes | No |
| transmembrane_predicted | transmembrane | OmniPath | No | No | Yes | Yes | No |
| transmembrane | transmembrane | GO_Intercell | No | No | Yes | Yes | No |
| transmembrane | transmembrane | CellPhoneDB | No | No | Yes | Yes | No |
Regulatory Interaction Network (28)
28 records.
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Protein Complex Composition (81)
81 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| HGF-Met complex | HGFMET | P08581P14210 | 2:2 | CompleatCORUMPDB | PDB:4k3jPDB:1shyPDB:4o3uPDB:7mo7PDB:7mo8PDB:7mobCORUM:2541PDB:7moaPDB:4o3tPDB:7mo9Compleat:HC3262 | 15161915 |
| MET-CIN85-SH3GL3-CBL complexHGF stimulated | CBLMETSH3GL3SH3KBP1 | P08581P22681Q96B97Q99963 | 1:1:1:1 | CompleatCORUM | Compleat:HC2699CORUM:2456 | 11894096 |
| Methyltransferase complexMETTL3-METTL14 | METTL14METTL3 | Q86U44Q9HCE5 | 1:1 | ComplexPortalPDB | PDB:7oegPDB:6ttwPDB:5l6ePDB:7oemPDB:7O0MPDB:7oqoPDB:7oejPDB:7o0qPDB:7o27PDB:7nidPDB:7rx8PDB:7nhiPDB:7niaPDB:7acdPDB:9g4wPDB:9g4sPDB:7o2fPDB:8bn8PDB:7nhjPDB:5l6dPDB:5k7mPDB:5K7MPDB:7o0pPDB:5K7UPDB:5il2PDB:7oedPDB:6y4gPDB:8pwbPDB:7rx7PDB:9g4uPDB:6ttxPDB:7rx6PDB:5il1PDB:7oeePDB:7nhvPDB:7o2hPDB:7o2iPDB:7oelPDB:7oqlPDB:7o0mPDB:7ni7PDB:5k7wPDB:5TEYPDB:7o0rPDB:6ttvPDB:7oqpPDB:7o28intact:EBI-58912060PDB:5il0PDB:6tu1PDB:7oekPDB:7oeiPDB:7oefPDB:8PWAPDB:7nhgPDB:7o08PDB:5IL0PDB:7OEKPDB:7o0lPDB:7O0LPDB:6tttPDB:7ni8PDB:7o09PDB:7ni9PDB:7oehPDB:6ttpPDB:5k7uPDB:7o2ePDB:8pwaPDB:7o2xPDB:8PW9PDB:8PW8PDB:5teyPDB:7o29PDB:7nhhPDB:8pw9 | 3835548338470714243167153734928414755292 |
| tRNA Methyltransferase Complex | METTL1WDR4 | P57081Q9UBP6 | 1:1 | CompleatComplexPortalPDB | PDB:8eg0PDB:8cthCompleat:HC594PDB:8ctiPDB:8h0nintact:EBI-12560184PDB:8d9kPDB:7u20PDB:8d58PDB:8d9l | 124034641475529236599985 |
| ATG4CGLUD2KLHL22METTL15RBFASCARF2SDHAF1SRGAP1 | A6NFY7A6NJ78P49448Q53GT1Q7Z6B7Q8N0V3Q96DT6Q96GP6 | 0:0:0:0:0:0:0:0 | hu.MAP2 | |||
| ATG4CGLUD2KLHL22METTL15RBFASCAF8SCARF2SDHAF1SRGAP1 | A6NFY7A6NJ78P49448Q53GT1Q7Z6B7Q8N0V3Q96DT6Q96GP6Q9UPN6 | 0:0:0:0:0:0:0:0:0 | hu.MAP2 | |||
| AURKAIP1DAP3METTL15MRPS10MRPS11MRPS12MRPS14MRPS15MRPS16MRPS17MRPS18BMRPS18CMRPS2MRPS21MRPS22MRPS23MRPS24MRPS25MRPS26MRPS27MRPS28MRPS31MRPS33MRPS34MRPS35MRPS5MRPS6MRPS7MRPS9PTCD3RBFA | A6NJ78O15235O60783P51398P82650P82663P82664P82673P82675P82912P82914P82921P82930P82932P82933Q8N0V3Q92552Q92665Q96EL2Q96EY7Q9BYN8Q9NWT8Q9Y291Q9Y2Q9Q9Y2R5Q9Y2R9Q9Y399Q9Y3D3Q9Y3D5Q9Y3D9Q9Y676 | 1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 | PDB | PDB:9g5cPDB:7pnzPDB:7pnxPDB:9g5dPDB:7pny | ||
| AURKAIP1DAP3METTL15MRPS10MRPS11MRPS12MRPS14MRPS15MRPS16MRPS17MRPS18BMRPS18CMRPS2MRPS21MRPS22MRPS23MRPS24MRPS25MRPS26MRPS27MRPS28MRPS31MRPS33MRPS34MRPS35MRPS5MRPS6MRPS7MRPS9PTCD3 | A6NJ78O15235O60783P51398P82650P82663P82664P82673P82675P82912P82914P82921P82930P82932P82933Q92552Q92665Q96EL2Q96EY7Q9BYN8Q9NWT8Q9Y291Q9Y2Q9Q9Y2R5Q9Y2R9Q9Y399Q9Y3D3Q9Y3D5Q9Y3D9Q9Y676 | 1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 | PDB | PDB:8qrl | ||
| METTL15RBFA | A6NJ78Q8N0V3 | 1:1 | hu.MAP2PDB | PDB:8iplPDB:8ipm | ||
| GTPBP1METTL16NFYAPLCB3 | O00178P23511Q01970Q86W50 | 0:0:0:0 | hu.MAP |
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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
Related Diseases (25)
Alzheimer diseaseBiliary tract cancerBrain cancerBreast cancerCardiovascular diseaseChronic arterial occlusive diseaseColorectal cancerFibrosisGlaucomaHead and neck cancerHeart diseaseInjuryLiver cancerLiver diseaseLung cancerMelanomaMetastatic lymph node neoplasmNasopharyngitisNon-small-cell lung cancerOvarian cancerRenal cell carcinomaSarcomaSolid tumour/cancerStomach cancerThyroid cancer
Biomarker
Phase 1/2; Phase 2; Phase 1; Phase 3; Discontinued in Phase 2; Approved; Preclinical
Drug Targets
FDA approved drug targets
Drugs (101)
FORETINIBGEFITINIBSELUMETINIBTIVANTINIBTEPOTINIBCABOZANTINIB S-MALATEOSIMERTINIBGLESATINIBANTI-MET MONOCLONAL ANTIBODY MIXTURE SYM015CAPMATINIBCETUXIMABROCILETINIBEMIBETUZUMABCHEMBL:CHEMBL546797BMS-754807BMS-777607NULLCEP-11981-SAR 125844.00DACTOLISIBTEREVALEFIMAMG-208PEMBROLIZUMABEUCALYPTIN AMACROCARPAL BMET TYROSINE KINASE INHIBITOR SGX523MITOGEN-ACTIVATED PROTEIN KINASE KINASE INHIBITORBMS-794833PF-04217903SAVOLITINIBTRAMETINIB DIMETHYL SULFOXIDEOLEOCANTHALEMB-01TAS-115VEMURAFENIBTELISOTUZUMABZM447439C-MET INHIBITOR AMG 208CRIZOTINIBCAPMATINIB HYDROCHLORIDESITRAVATINIBMK-8033MK-2461GALLOCATECHIN GALLATEEMD-1204831TELISOTUZUMAB VEDOTINPF-562271TEPOTINIB HYDROCHLORIDEBMS-698769ALTIRATINIBNVP-TAE684ONARTUZUMABEPIGALLOCATECHIN-3-GALLATECMX-2043PD-0166285SP-600125YUANHUADINELAPATINIBSU11274BMS-817378AMG-337PAZOPANIBMERESTINIBPHA-665752PALBOCICLIBCP-547632ERLOTINIBSGX-523JNJ-38877605AMUVATINIBANTI-C-MET MONOCLONAL ANTIBODY SAIT301CHEMBL:CHEMBL1997335MACROCARPAL AGOLVATINIBENTRECTINIBBEPERMINOGENE PERPLASMIDANTI-MET/EGFR MONOCLONAL ANTIBODY LY3164530TAMATINIBCHEMBL:CHEMBL399530CRENOLANIBRITUXIMABSNS-314C-MET INHIBITOR MK2461C-MET INHIBITOR AMG 337PANITUMUMABC-MET INHIBITORARRY-300BPI-9016ILORASERTIBTYROSOL SINAPATECENISERTIBCYC-116EPICATECHIN GALLATENINGETINIBAPRATOXIN FAMIVANTAMAB-VMJWLINIFANIBANTI-EGFR MONOCLONAL ANTIBODYVEBRELTINIBBAY 61-3606JNJ-7706621
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. |