P08581

PTMD Annotation Information

※ Protein Information

Tag Content
UniProt Accession MET_HUMAN; P08581;
Entrez ID 4233
GenBank Protein ID NM_000245.3; NM_001127500.2;
GenBank Nucleotide ID NP_000236.2; NP_001120972.1;
Protein Name 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)
Gene Name MET
Organism Homo sapiens
NCBI Taxa ID 9606
Functional DescriptionReceptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment (view all)
Sequence
(Fasta)		MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH 60
HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD CSSKANLSGG VWKDNINMAL 120
VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 180
GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE 240
FRDSYPIKYV HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL 300
TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK PDSAEPMDRS 360
AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR TLLRNSSGCE ARRDEYRTEF 420
TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 480
LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 540
CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK 600
TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT 660
SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 720
AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV SVPRMVINVH 780
EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV 840
FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL 900
LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISTALLLLLG FFLWLKKRKQ 960
IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS 1020
CRQVQYPLTD MSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF 1080
NEVIGRGHFG CVYHGTLLDN DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL 1140
SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 1200
VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF 1260
TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 1320
HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD 1380
TRPASFWETS 1391

※ PTM-Disease Association

NumPTMDiseaseCell TypeTypePTM SitePMID
1GlycosylationHepatocellular carcinoma/Hepatocarcinoma/HepatomaP23832667
[Reference]: C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization
2PhosphorylationNon-small cell lung cancer/carcinomaP23794705
[Reference]: EGF receptor activates MET through MAPK to enhance non-small cell lung carcinoma invasion and brain metastasis
3UbiquitinationPolycystic kidney diseaseP20852388
[Reference]: Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease
4PhosphorylationGlioblastomaP22789536
[Reference]: Overall, MET phosphorylation was associated with tumor cell invasion, increased N-cadherin, and decreased T-cadherin expression
5PhosphorylationChondrosarcomaU12183053
[Reference]: CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine phosphorylation of c-Met receptor protein in human chondrosarcoma cells.
6PhosphorylationColon cancer/carcinomaU24665413
[Reference]: phosphorylation of Threonine 192 in Claudin-3 leads to disruption of TJs in an ovarian cancer cell line24 and increased phosphorylation of its C-terminal tyrosines was found in EGFR and c-MET positive colon cancer cells
7Tyrosine PhosphorylationLung cancer/carcinomaPY100322181983
[Reference]: In addition, high expression of two specific forms of phosphorylated MET--cytoplasmic expression of Y1003 and nuclear expression of Y1365--appeared to correlate with a worse overall survival (P = .016; hazard ratio [HR], 1.86; 95% confidence interval [95% CI], 1.12- 3.07; and P = .034; HR, 1.70; 95% CI, 1.04-2.78, respectively).
8Tyrosine PhosphorylationBladder cancerUY100317062641
[Reference]: The phosphorylated 145-kDa protein was identified as the beta-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145(met), in which tyrosine residues 1003, 1234, and 1235 were phosphorylated.
9Tyrosine PhosphorylationLung cancer/carcinomaPY123423973484
[Reference]: we discovered that knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro.
10Tyrosine PhosphorylationHepatocellular carcinoma/Hepatocarcinoma/HepatomaUY123421455220
[Reference]: Abl interconnects oncogenic Met and p53 core pathways in cancer cells.
11Tyrosine PhosphorylationBladder cancerUY123417062641
[Reference]: The phosphorylated 145-kDa protein was identified as the beta-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145(met), in which tyrosine residues 1003, 1234, and 1235 were phosphorylated.
12Tyrosine PhosphorylationLung cancer/carcinomaPY123523973484
[Reference]: we discovered that knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro.
13Tyrosine PhosphorylationHepatocellular carcinoma/Hepatocarcinoma/HepatomaUY123521455220
[Reference]: Abl interconnects oncogenic Met and p53 core pathways in cancer cells.
14Tyrosine PhosphorylationBladder cancerUY123517062641
[Reference]: The phosphorylated 145-kDa protein was identified as the beta-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145(met), in which tyrosine residues 1003, 1234, and 1235 were phosphorylated. Inhibitors of Src (PP2, SU6656) or EGFR (AG99), but not p145(met) (K252a), effectively blocked tyrosine phosphorylation of p145(met) and promoted cell death accompanied by activation of caspase-like proteases.?
15Tyrosine PhosphorylationRenal cancer/carcinomaUY134916914575
[Reference]: Median rates (range) of cancer cells immunopositive for pY1234/pY1235 HGFR/c-Met and pY1349 HGFR/c-Met in the tumor sections were 0% (0-5.2%) and 14.3% (0-64.3%), respectively. Positive expression of pY1349 HGFR/c-Met was significantly associated with high pT stage, presence of metastasis, and high-grade carcinoma.
16Tyrosine PhosphorylationLung cancer/carcinomaPY136522181983
[Reference]: In addition, high expression of two specific forms of phosphorylated MET--cytoplasmic expression of Y1003 and nuclear expression of Y1365--appeared to correlate with a worse overall survival (P = .016; hazard ratio [HR], 1.86; 95% confidence interval [95% CI], 1.12- 3.07; and P = .034; HR, 1.70; 95% CI, 1.04-2.78, respectively).

※ Disease Cross-ref Annotation

DatabaseAnnotation
Cancer Gene Census
papillary renal, head-neck squamous cell papillary renal familial papillary renal cancer
CTD (Curated)
(count: 27)
(view all)		MESH:D000230 ; Adenocarcinoma
MESH:D001254 ; Astrocytoma
MESH:D001321 ; Autistic Disorder
MESH:D002277 ; Carcinoma
MESH:D006528 ; Carcinoma, Hepatocellular
MESH:D002292 ; Carcinoma, Renal Cell
DisGeNet (Curated)
(count: 33)
(view all)		C0001418; Adenocarcinoma
C0004114; Astrocytoma
C0004352; Autistic Disorder
C0007131; Non-Small Cell Lung Carcinoma
C0007134; Renal Cell Carcinoma
C0007137; Squamous cell carcinoma
HGMD
(count: 15)
(view all)		CM033395; Gastric cancer; Missense/nonsense
CM068009; Diffuse large B-cell lymphoma ?; Missense/nonsense
CM002809; Gastric cancer; Missense/nonsense
CM990852; Papillary renal carcinoma; Missense/nonsense
CM981285; Papillary renal carcinoma; Missense/nonsense
CM993668; Papillary renal carcinoma; Missense/nonsense
GWASdb
(count: 6)		rs38841; Type 2 diabetes; type 2 diabetes mellitus
rs10487353; Cognitive impairment induced by topiramate; cognitive disorder
rs10243024; Multiple sclerosis (severity); multiple sclerosis
rs38852; Serum metabolites; Null
rs38855; Triglycerides; coronary artery disease|lipid metabolism disorder|arteriosclerosis
rs2402118; Cognitive impairment induced by topiramate; cognitive disorder

※ PTM Sites

PTM Modification Sites
Phosphorylation
(count: 50)
(view all)		 1000      TEMVSNESVDYRATF     dbPAF
1003      VSNESVDYRATFPED     dbPAF
1006      ESVDYRATFPEDQFP     dbPAF
1016      EDQFPNSSQNGSCRQ     dbPAF
1020      PNSSQNGSCRQVQYP     dbPAF
1026      GSCRQVQYPLTDMSP     dbPAF
Acetylation
(count: 1)		 1110      KKIHCAVKSLNRITD     PLMD
Ubiquitination
(count: 22)
(view all)		 1103      TLLDNDGKKIHCAVK     PLMD
1110      KKIHCAVKSLNRITD     PLMD
1161      LVVLPYMKHGDLRNF     PLMD
1179      ETHNPTVKDLIGFGL     PLMD
1190      GFGLQVAKGMKYLAS     PLMD
1193      LQVAKGMKYLASKKF     PLMD

※ Protein-Protein Interaction

NetworkInteraction
ABSource