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)
Protein symbol MET | UniProt ID | EVMP score 0.38 |
Frequency 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
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteinsTransporters
Protein Function
- 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
- Human disease related genes:Cancers:Cancers of the urinary system
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- FDA approved drug targets:Biotech drugs
Transmembrane
933..955; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
DFNB97HGFRRCCP2
Gene Description
MET proto-oncogene, receptor tyrosine kinase
Chromosome
7
Position
116672196-116798377
Frequency
3
EVMP Score
0.38
Fluorescence & Localization
Tissue SpecificintestineBrain Regional Specificbasal gangliaCell SpecificAdipocytesSingle-Nuclei Brain Specificlower rhombic lipBlood Cell SpecificneutrophilBlood Lineage Specificgranulocytes
Function & Pathway
Protein Function
- 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
- Human disease related genes:Cancers:Cancers of the urinary system
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- FDA approved drug targets:Biotech drugs
Cellular Component
Molecular Function
- 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
KEGG
- 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
- KEGG:hsa04520 Adherens junction
- KEGG:hsa05100 Bacterial invasion of epithelial cells
- KEGG:hsa05120 Epithelial cell signaling in Helicobacter pylori infection
- KEGG:hsa05144 Malaria
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05202 Transcriptional misregulation in cancer
- KEGG:hsa05205 Proteoglycans in cancer
- KEGG:hsa05206 MicroRNAs in cancer
- KEGG:hsa05208 Chemical carcinogenesis - reactive oxygen species
- KEGG:hsa05211 Renal cell carcinoma
- KEGG:hsa05218 Melanoma
- KEGG:hsa05223 Non-small cell lung cancer
- KEGG:hsa05225 Hepatocellular carcinoma
- KEGG:hsa05226 Gastric cancer
- KEGG:hsa05230 Central carbon metabolism in cancer
Reactome
- 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
- R-hsa-8851907 met activates pi3k akt signaling
- R-hsa-8874081 met activates ptk2 signaling
- R-hsa-8865999 met activates ptpn11
- R-hsa-8875555 met activates rap1 and rac1
- R-hsa-8851805 met activates ras signaling
- R-hsa-8875513 met interacts with tns proteins
- R-hsa-8875878 met promotes cell motility
- R-hsa-6806942 met receptor activation
- R-hsa-8875656 met receptor recycling
- R-hsa-9856651 mitf m dependent gene expression
- R-hsa-9730414 mitf m regulated melanocyte development
- R-hsa-6807004 negative regulation of met activity
- R-hsa-199418 negative regulation of the pi3k akt network
- R-hsa-9675108 nervous system development
- R-hsa-2219528 pi3k akt signaling in cancer
- R-hsa-9825892 regulation of mitf m dependent genes involved in cell cycle and proliferation
- R-hsa-73857 rna polymerase ii transcription
- R-hsa-400685 sema4d in semaphorin signaling
- R-hsa-416550 sema4d mediated inhibition of cell attachment and migration
- R-hsa-373755 semaphorin interactions
- R-hsa-6806834 signaling by met
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-8986944 transcriptional regulation by mecp2
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
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 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 |
Regulatory Interaction Network
28 records.
Protein Complex Composition
81 records.
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
- Protein kinase superfamily
- Tyr protein kinase family
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Clinical Relevance
Disease Involvement
Cancer-related genesDeafnessDisease variantFDA approved drug targetsNon-syndromic deafnessProto-oncogene
Related Diseases
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
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
ENSG00000010017ENSG00000019991ENSG00000103423ENSG00000110395ENSG00000146648ENSG00000197122
Interaction Count
6
Interaction Dataset
intact_biogrid