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P08581 (MET_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 197. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte growth factor receptor

Short name=HGF receptor
EC=2.7.10.1
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name=SF receptor
Tyrosine-protein kinase Met
Gene names
Name:MET
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1390 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor 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 of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. Ref.14 Ref.17 Ref.25

Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells. Ref.14 Ref.17 Ref.25

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity.

Subunit structure

Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4 By similarity. Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10. Interacts with PTPN1 and PTPN2. Ref.12 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.35 Ref.49

Subcellular location

Membrane; Single-pass type I membrane protein.

Isoform 3: Secreted.

Tissue specificity

Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. Ref.11 Ref.13

Domain

The kinase domain is involved in SPSB1 binding.

The beta-propeller Sema domain mediates binding to HGF.

Post-translational modification

Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2. Ref.15 Ref.16 Ref.23 Ref.26 Ref.28

Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. Ref.21

Involvement in disease

Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.

Defects in MET may be associated with gastric cancer.

Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.44

Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.41 Ref.42 Ref.43 Ref.45 Ref.46

A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes.

MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies. Ref.52

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 3 IPT/TIG domains.

Contains 1 protein kinase domain.

Contains 1 Sema domain.

Ontologies

Keywords
   Cellular componentMembrane
Secreted
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Proto-oncogene
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

adult behavior

Inferred from electronic annotation. Source: Ensembl

axon guidance

Traceable author statement. Source: Reactome

brain development

Inferred from electronic annotation. Source: Ensembl

branching morphogenesis of an epithelial tube

Inferred from mutant phenotype PubMed 16153003. Source: UniProtKB

cell proliferation

Traceable author statement PubMed 10871856. Source: ProtInc

cell surface receptor signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

muscle cell migration

Inferred from electronic annotation. Source: Ensembl

myoblast proliferation

Inferred from electronic annotation. Source: Ensembl

myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of hydrogen peroxide-mediated programmed cell death

Inferred from mutant phenotype PubMed 20655899. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Non-traceable author statement Ref.8. Source: GOC

placenta development

Inferred from electronic annotation. Source: Ensembl

positive chemotaxis

Inferred from direct assay PubMed 15218527. Source: UniProtKB

positive regulation of endothelial cell chemotaxis

Inferred from mutant phenotype PubMed 19850054. Source: UniProtKB

positive regulation of glucose transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 22521434. Source: BHF-UCL

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling

Inferred from electronic annotation. Source: Ensembl

semaphorin-plexin signaling pathway

Inferred from direct assay PubMed 15218527. Source: UniProtKB

signal transduction

Traceable author statement Ref.14. Source: ProtInc

skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasal plasma membrane

Inferred from direct assay Ref.25. Source: MGI

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Non-traceable author statement Ref.1. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.14. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

hepatocyte growth factor-activated receptor activity

Traceable author statement PubMed 10871856. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 11571281. Source: UniProtKB

protein phosphatase binding

Inferred from physical interaction Ref.28. Source: UniProtKB

protein tyrosine kinase activity

Non-traceable author statement Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CBLP2268114EBI-1039152,EBI-518228
DNAJA3Q96EY1-22EBI-1039152,EBI-3952284
EGFRP005337EBI-1039152,EBI-297353
FGRP097692EBI-1039152,EBI-1383732
HGFP142104EBI-1039152,EBI-1039104
HGFP14210-62EBI-1039152,EBI-6280319
inlBP251474EBI-1039152,EBI-1379295From a different organism.
INPPL1O153572EBI-1039152,EBI-1384248
KDRP359683EBI-1039152,EBI-1005487
KdrP359183EBI-1039152,EBI-1555005From a different organism.
LCKP062393EBI-1039152,EBI-1348
LYNP079482EBI-1039152,EBI-79452
MUC1P159412EBI-1039152,EBI-2804728
NCK1P163332EBI-1039152,EBI-389883
NCK2O436392EBI-1039152,EBI-713635
PIK3R1P279866EBI-1039152,EBI-79464
PIK3R2O0045911EBI-1039152,EBI-346930
PIK3R3Q9256911EBI-1039152,EBI-79893
PLCG1P1917410EBI-1039152,EBI-79387
PLXNB1O431577EBI-1039152,EBI-1111488
PLXNB2O150312EBI-1039152,EBI-722004
PLXNB3Q9ULL42EBI-1039152,EBI-311073
PTK2Q009445EBI-1039152,EBI-2896409From a different organism.
PTPN1P180313EBI-1039152,EBI-968788
PTPN11Q0612413EBI-1039152,EBI-297779
PTPRBP234672EBI-1039152,EBI-1265766
PTPRJQ129135EBI-1039152,EBI-2264500
RASA1P2093615EBI-1039152,EBI-1026476
SH2B3Q9UQQ22EBI-1039152,EBI-7879749
SH2D1AO608803EBI-1039152,EBI-6983382
SH2D1BO147966EBI-1039152,EBI-3923013
SH2D2AQ9NP317EBI-1039152,EBI-490630
SH2D3CQ8N5H74EBI-1039152,EBI-745980
SHBQ154644EBI-1039152,EBI-4402156
SHC1P293535EBI-1039152,EBI-78835
SHC2P980772EBI-1039152,EBI-7256023
SHC4Q6S5L83EBI-1039152,EBI-9453524
SHDQ96IW22EBI-1039152,EBI-4402781
SLA2Q9H6Q34EBI-1039152,EBI-1222854
SOCS5O751592EBI-1039152,EBI-970130
SOCS6O145444EBI-1039152,EBI-3929549
SRCP129314EBI-1039152,EBI-621482
STAP1Q9ULZ23EBI-1039152,EBI-6083058
SYKP434053EBI-1039152,EBI-78302
TECP426802EBI-1039152,EBI-1383480
TENC1Q63HR22EBI-1039152,EBI-949753
TNS1Q9HBL02EBI-1039152,EBI-3389814
TNS3Q68CZ23EBI-1039152,EBI-1220488
VAV3Q9UKW42EBI-1039152,EBI-297568
YES1P079473EBI-1039152,EBI-515331
ZAP70P434032EBI-1039152,EBI-1211276

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional soluble isoforms seem to exist.
Isoform 1 (identifier: P08581-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P08581-2)

The sequence of this isoform differs from the canonical sequence as follows:
     755-755: S → STWWKEPLNIVSFLFCFAS
Note: No experimental confirmation available.
Isoform 3 (identifier: P08581-3)

Also known as: Soluble MET variant 4;

The sequence of this isoform differs from the canonical sequence as follows:
     755-764: SGGSTITGVG → RHVNIALIQR
     765-1390: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 13901366Hepatocyte growth factor receptor
PRO_0000024440

Regions

Topological domain25 – 932908Extracellular Potential
Transmembrane933 – 95523Helical; Potential
Topological domain956 – 1390435Cytoplasmic Potential
Domain27 – 515489Sema
Domain563 – 65593IPT/TIG 1
Domain657 – 73983IPT/TIG 2
Domain742 – 83695IPT/TIG 3
Domain1078 – 1345268Protein kinase
Nucleotide binding1084 – 10929ATP By similarity
Region1212 – 1390179Interaction with RANBP9
Region1320 – 135940Interaction with MUC20

Sites

Active site12041Proton acceptor By similarity
Binding site11101ATP
Site307 – 3082Cleavage Potential
Site1009 – 10102Breakpoint for translocation to form TPR-MET oncogene

Amino acid modifications

Modified residue9771Phosphothreonine Ref.29
Modified residue9901Phosphoserine Ref.30
Modified residue9971Phosphoserine Ref.30
Modified residue10001Phosphoserine Ref.30
Modified residue10031Phosphotyrosine Ref.29 Ref.32
Modified residue12301Phosphotyrosine Ref.23
Modified residue12341Phosphotyrosine; by autocatalysis Ref.23
Modified residue12351Phosphotyrosine; by autocatalysis Ref.15 Ref.23
Modified residue12891Phosphothreonine Ref.32
Modified residue13491Phosphotyrosine; by autocatalysis Ref.16 Ref.23
Modified residue13561Phosphotyrosine; by autocatalysis Ref.16 Ref.26
Modified residue13651Phosphotyrosine Ref.23
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Ref.31
Glycosylation1491N-linked (GlcNAc...) Potential
Glycosylation2021N-linked (GlcNAc...) Potential
Glycosylation3991N-linked (GlcNAc...) Potential
Glycosylation4051N-linked (GlcNAc...) Potential
Glycosylation6071N-linked (GlcNAc...) Potential
Glycosylation6351N-linked (GlcNAc...) Potential
Glycosylation7851N-linked (GlcNAc...) Potential
Glycosylation8791N-linked (GlcNAc...) Potential
Glycosylation9301N-linked (GlcNAc...) Potential
Disulfide bond95 ↔ 101 Ref.38 Ref.39 Ref.40
Disulfide bond98 ↔ 160 Ref.38 Ref.39 Ref.40
Disulfide bond133 ↔ 141 Ref.38 Ref.39 Ref.40
Disulfide bond172 ↔ 175 Ref.38 Ref.39 Ref.40
Disulfide bond298 ↔ 363 Ref.38 Ref.39 Ref.40
Disulfide bond385 ↔ 397 Ref.38 Ref.39 Ref.40
Disulfide bond520 ↔ 538 Ref.38 Ref.39 Ref.40
Disulfide bond526 ↔ 561 Ref.38 Ref.39 Ref.40
Disulfide bond529 ↔ 545 Ref.38 Ref.39 Ref.40
Disulfide bond541 ↔ 551 Ref.38 Ref.39 Ref.40

Natural variations

Alternative sequence755 – 76410SGGSTITGVG → RHVNIALIQR in isoform 3.
VSP_042447
Alternative sequence7551S → STWWKEPLNIVSFLFCFAS in isoform 2.
VSP_005005
Alternative sequence765 – 1390626Missing in isoform 3.
VSP_042448
Natural variant1431R → Q. Ref.51
Corresponds to variant rs35469582 [ dbSNP | Ensembl ].
VAR_041738
Natural variant1501H → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.52
VAR_064855
Natural variant1561S → L. Ref.51
Corresponds to variant rs56311081 [ dbSNP | Ensembl ].
VAR_041739
Natural variant1681E → D Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.51 Ref.52
Corresponds to variant rs55985569 [ dbSNP | Ensembl ].
VAR_041740
Natural variant2381L → S.
Corresponds to variant rs34349517 [ dbSNP | Ensembl ].
VAR_032478
Natural variant3161I → M.
Corresponds to variant rs35225896 [ dbSNP | Ensembl ].
VAR_032479
Natural variant3201A → V. Ref.41
Corresponds to variant rs35776110 [ dbSNP | Ensembl ].
VAR_006285
Natural variant3751N → S. Ref.51
Corresponds to variant rs33917957 [ dbSNP | Ensembl ].
VAR_032480
Natural variant3851C → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.52
VAR_064856
Natural variant7731P → L in gastric cancer. Ref.48
VAR_032481
Natural variant9701R → C. Ref.50 Ref.51
Corresponds to variant rs34589476 [ dbSNP | Ensembl ].
VAR_032482
Natural variant9911P → S in gastric cancer; prolonged tyrosine phosphorylation in response to HGF/SF; transforming activity in athymic nude mice. Ref.47
VAR_032483
Natural variant9921T → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.47 Ref.50 Ref.51 Ref.52
Corresponds to variant rs56391007 [ dbSNP | Ensembl ].
VAR_032484
Natural variant10921V → I in RCCP; constitutive autophosphorylation. Ref.43 Ref.45 Ref.46
VAR_032485
Natural variant10941H → L in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.46
VAR_032486
Natural variant10941H → R in RCCP; causes malignant transformation in cell lines. Ref.42 Ref.43
VAR_032487
Natural variant10941H → Y in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.46
VAR_032488
Natural variant11061H → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.43 Ref.46
VAR_032489
Natural variant11311M → T in RCCP; germline mutation. Ref.41 Ref.43
VAR_006286
Natural variant11731T → I in HCC. Ref.44
VAR_032490
Natural variant11881V → L in RCCP; germline mutation. Ref.41 Ref.43
VAR_006287
Natural variant11951L → V in RCCP; somatic mutation. Ref.41
VAR_006288
Natural variant12201V → I in RCCP; germline mutation. Ref.41
VAR_006289
Natural variant12281D → H in RCCP; somatic mutation. Ref.41
VAR_006291
Natural variant12281D → N in RCCP; germline mutation. Ref.41
VAR_006290
Natural variant12301Y → C in RCCP; germline mutation. Ref.41 Ref.43
VAR_006292
Natural variant12301Y → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.43 Ref.46
VAR_032491
Natural variant12301Y → H in RCCP; somatic mutation. Ref.41
VAR_006293
Natural variant12441K → R in HCC. Ref.44
VAR_032492
Natural variant12501M → I in HCC. Ref.44
VAR_032493
Natural variant12501M → T in RCCP; somatic mutation. Ref.41 Ref.43
VAR_006294
Natural variant12941V → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.52
VAR_064857

Experimental info

Mutagenesis12341Y → F: Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1235. Ref.28
Mutagenesis12351Y → F: Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1234. Ref.28
Sequence conflict2371V → A in ACF47606. Ref.3
Sequence conflict5081K → R in ACF47606. Ref.3
Sequence conflict7201F → S in ACF47606. Ref.3
Sequence conflict11911G → A in AAA59591. Ref.1
Sequence conflict12721L → V in AAA59591. Ref.1
Sequence conflict12721L → V in CAB56793. Ref.2
Sequence conflict12721L → V in AAA59590. Ref.6

Secondary structure

................................................................................................................................................................................................ 1390
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 7, 2009. Version 4.
Checksum: 9CF896D1273905C3

FASTA1,390155,541
        10         20         30         40         50         60 
MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH 

        70         80         90        100        110        120 
HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD CSSKANLSGG VWKDNINMAL 

       130        140        150        160        170        180 
VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 

       190        200        210        220        230        240 
GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE 

       250        260        270        280        290        300 
FRDSYPIKYV HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL 

       310        320        330        340        350        360 
TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK PDSAEPMDRS 

       370        380        390        400        410        420 
AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR TLLRNSSGCE ARRDEYRTEF 

       430        440        450        460        470        480 
TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 

       490        500        510        520        530        540 
LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 

       550        560        570        580        590        600 
CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK 

       610        620        630        640        650        660 
TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT 

       670        680        690        700        710        720 
SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 

       730        740        750        760        770        780 
AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV SVPRMVINVH 

       790        800        810        820        830        840 
EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV 

       850        860        870        880        890        900 
FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL 

       910        920        930        940        950        960 
LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISTALLLLLG FFLWLKKRKQ 

       970        980        990       1000       1010       1020 
IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS 

      1030       1040       1050       1060       1070       1080 
CRQVQYPLTD MSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF 

      1090       1100       1110       1120       1130       1140 
NEVIGRGHFG CVYHGTLLDN DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL 

      1150       1160       1170       1180       1190       1200 
SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 

      1210       1220       1230       1240       1250       1260 
VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF 

      1270       1280       1290       1300       1310       1320 
TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 

      1330       1340       1350       1360       1370       1380 
HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD 

      1390 
TRPASFWETS 

« Hide

Isoform 2 [UniParc].

Checksum: C5F64DCBBC13CC88
Show »

FASTA1,408157,712
Isoform 3 (Soluble MET variant 4) [UniParc].

Checksum: BBCBC4197C9C18DE
Show »

FASTA76485,745

References

« Hide 'large scale' references
[1]"Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors."
Park M., Dean M., Kaul K., Braun M.J., Gonda M.A., Vande Woude G.
Proc. Natl. Acad. Sci. U.S.A. 84:6379-6383(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]Giordano S.
Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[8]"Primary structure of the met protein tyrosine kinase domain."
Chan A.M.-L., King H.W.S., Tempest P.R., Deakin E.A., Cooper C.S., Brookes P.
Oncogene 1:229-233(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1010-1390.
[9]"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes."
Lee S.-T., Strunk K.M., Spritz R.A.
Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1206-1264.
[10]"The human met oncogene is related to the tyrosine kinase oncogenes."
Dean M., Park M., le Beau M.M., Robins T.S., Diaz M.O., Rowley J.D., Blair D.G., Vande Woude G.F.
Nature 318:385-388(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1267-1390.
[11]"The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors."
Prat M., Narsimhan R.P., Crepaldi T., Nicotra M.R., Natali P.G., Comoglio P.M.
Int. J. Cancer 49:323-328(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[12]"The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase."
Graziani A., Gramaglia D., Cantley L.C., Comoglio P.M.
J. Biol. Chem. 266:22087-22090(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIK3R1.
[13]"Expression of the Met/HGF receptor in normal and neoplastic human tissues."
Di Renzo M.F., Narsimhan R.P., Olivero M., Bretti S., Giordano S., Medico E., Gaglia P., Zara P., Comoglio P.M.
Oncogene 6:1997-2003(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[14]"Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product."
Bottaro D.P., Rubin J.S., Faletto D.L., Chan A.M.-L., Kmiecik T.E., Vande Woude G.F., Aaronson S.A.
Science 251:802-804(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase."
Ferracini R., Longati P., Naldini L., Vigna E., Comoglio P.M.
J. Biol. Chem. 266:19558-19564(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-1235, ATP-BINDING SITE LYS-1110.
[16]"A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family."
Ponzetto C., Bardelli A., Zhen Z., Maina F., dalla Zonca P., Giordano S., Graziani A., Panayotou G., Comoglio P.M.
Cell 77:261-271(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION AT TYR-1349 AND TYR-1356, INTERACTION WITH SRC; PLCG1 AND GRB2.
[17]"Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium."
Nusrat A., Parkos C.A., Bacarra A.E., Godowski P.J., Delp-Archer C., Rosen E.M., Madara J.L.
J. Clin. Invest. 93:2056-2065(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN WOUND HEALING.
[18]"Induction of epithelial tubules by growth factor HGF depends on the STAT pathway."
Boccaccio C., Ando M., Tamagnone L., Bardelli A., Michieli P., Battistini C., Comoglio P.M.
Nature 391:285-288(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAT3.
[19]"Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis."
Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., Swamy O.R., Leone M.E., Riedel H.
Mol. Cell. Biol. 19:6217-6228(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB10.
[20]"Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM."
Wang D., Li Z., Messing E.M., Wu G.
J. Biol. Chem. 277:36216-36222(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP9.
[21]"c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination."
Taher T.E., Tjin E.P., Beuling E.A., Borst J., Spaargaren M., Pals S.T.
J. Immunol. 169:3793-3800(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[22]"The semaphorin 4D receptor controls invasive growth by coupling with Met."
Giordano S., Corso S., Conrotto P., Artigiani S., Gilestro G., Barberis D., Tamagnone L., Comoglio P.M.
Nat. Cell Biol. 4:720-724(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLXNB1.
[23]"Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1."
Palka H.L., Park M., Tonks N.K.
J. Biol. Chem. 278:5728-5735(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-1230; TYR-1234; TYR-1235; TYR-1349 AND TYR-1365, DEPHOSPHORYLATION BY PTPRJ AT TYR-1349 AND TYR-1365.
[24]"A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling."
Wang D., Li Z., Schoen S.R., Messing E.M., Wu G.
Biochem. Biophys. Res. Commun. 313:320-326(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP9 AND RANBP10.
[25]"MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met."
Higuchi T., Orita T., Katsuya K., Yamasaki Y., Akiyama K., Li H., Yamamoto T., Saito Y., Nakamura M.
Mol. Cell. Biol. 24:7456-7468(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MUC20.
[26]"The SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading."
Koch A., Mancini A., El Bounkari O., Tamura T.
Oncogene 24:3436-3447(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-1356, INTERACTION WITH INPPL1.
[27]"Invasive growth: a MET-driven genetic programme for cancer and stem cells."
Boccaccio C., Comoglio P.M.
Nat. Rev. Cancer 6:637-645(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN ANGIOGENESIS.
[28]"Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase."
Sangwan V., Paliouras G.N., Abella J.V., Dube N., Monast A., Tremblay M.L., Park M.
J. Biol. Chem. 283:34374-34383(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN1 AND PTPN2, INTERACTION WITH PTPN1 AND PTPN2, MUTAGENESIS OF TYR-1234 AND TYR-1235.
[29]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-977 AND TYR-1003, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[30]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990; SER-997 AND SER-1000, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[31]"Identification of N-glycosylation sites on secreted proteins of human hepatocellular carcinoma cells with a complementary proteomics approach."
Cao J., Shen C., Wang H., Shen H., Chen Y., Nie A., Yan G., Lu H., Liu Y., Yang P.
J. Proteome Res. 8:662-672(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106.
Tissue: Hepatoma.
[32]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1003 AND THR-1289, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas."
Mahtouk K., Tjin E.P., Spaargaren M., Pals S.T.
Biochim. Biophys. Acta 1806:208-219(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[34]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET."
Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., Bodepudi S., Ashkenazi A.
J. Biol. Chem. 286:32762-32774(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GAB1.
[36]"Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex."
Schiering N., Casale E., Caccia P., Giordano P., Battistini C.
Biochemistry 39:13376-13382(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1356-1359 IN COMPLEX WITH GRB2.
[37]"Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a."
Schiering N., Knapp S., Marconi M., Flocco M.M., Cui J., Perego R., Rusconi L., Cristiani C.
Proc. Natl. Acad. Sci. U.S.A. 100:12654-12659(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1049-1360 IN COMPLEX WITH INHIBITOR.
[38]"Insights into function of PSI domains from structure of the Met receptor PSI domain."
Kozlov G., Perreault A., Schrag J.D., Park M., Cygler M., Gehring K., Ekiel I.
Biochem. Biophys. Res. Commun. 321:234-240(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 519-562, DISULFIDE BONDS.
[39]"Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor."
Stamos J., Lazarus R.A., Yao X., Kirchhofer D., Wiesmann C.
EMBO J. 23:2325-2335(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.22 ANGSTROMS) OF 25-567 IN COMPLEX WITH HGF, DISULFIDE BONDS.
[40]"Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB."
Niemann H.H., Jager V., Butler P.J., van den Heuvel J., Schmidt S., Ferraris D., Gherardi E., Heinz D.W.
Cell 130:235-246(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-740 IN COMPLEX WITH L.MONOCYTOGENES INLB, DISULFIDE BONDS.
[41]"Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas."
Schmidt L., Duh F.-M., Chen F., Kishida T., Glenn G., Choyke P., Scherer S.W., Zhuang Z., Lubensky I., Dean M., Allikmets R., Chidambaram A., Bergerheim U.R., Feltis J.T., Casadevall C., Zamarron A., Bernues M., Richard S. expand/collapse author list , Lips C.J.M., Walther M.M., Tsui L.-C., Geil L., Orcutt M.L., Stackhouse T., Lipan J., Slife L., Brauch H., Decker J., Niehans G., Hughson M.D., Moch H., Storkel S., Lerman M.I., Linehan W.M., Zbar B.
Nat. Genet. 16:68-73(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RCCP THR-1131; LEU-1188; VAL-1195; ILE-1220; HIS-1228; ASN-1228; CYS-1230; HIS-1230 AND THR-1250, VARIANT VAL-320.
[42]"Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene."
Schmidt L., Junker K., Weirich G., Glenn G., Choyke P., Lubensky I., Zhuang Z., Jeffers M., Vande Woude G., Neumann H., Walther M., Linehan W.M., Zbar B.
Cancer Res. 58:1719-1722(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RCCP ARG-1094, CHARACTERIZATION OF VARIANT RCCP ARG-1094.
[43]"Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype."
Lubensky I.A., Schmidt L., Zhuang Z., Weirich G., Pack S., Zambrano N., Walther M.M., Choyke P., Linehan W.M., Zbar B.
Am. J. Pathol. 155:517-526(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RCCP ILE-1092; ARG-1094; ASP-1106; THR-1131; LEU-1188; ASP-1230; CYS-1230 AND THR-1250.
[44]"Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas."
Park W.S., Dong S.M., Kim S.Y., Na E.Y., Shin M.S., Pi J.H., Kim B.J., Bae J.H., Hong Y.K., Lee K.S., Lee S.H., Yoo N.J., Jang J.J., Pack S., Zhuang Z., Schmidt L., Zbar B., Lee J.Y.
Cancer Res. 59:307-310(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HCC ILE-1173; ARG-1244 AND ILE-1250.
[45]"Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family."
Olivero M., Valente G., Bardelli A., Longati P., Ferrero N., Cracco C., Terrone C., Rocca-Rossetti S., Comoglio P.M., Di Renzo M.F.
Int. J. Cancer 82:640-643(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RCCP ILE-1092, CHARACTERIZATION OF VARIANT RCCP ILE-1092.
[46]"Novel mutations of the MET proto-oncogene in papillary renal carcinomas."
Schmidt L., Junker K., Nakaigawa N., Kinjerski T., Weirich G., Miller M., Lubensky I., Neumann H.P.H., Brauch H., Decker J., Vocke C., Brown J.A., Jenkins R., Richard S., Bergerheim U., Gerrard B., Dean M., Linehan W.M., Zbar B.
Oncogene 18:2343-2350(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230, CHARACTERIZATION OF VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230.
[47]"A novel germ line juxtamembrane Met mutation in human gastric cancer."
Lee J.-H., Han S.-U., Cho H., Jennings B., Gerrard B., Dean M., Schmidt L., Zbar B., Vande Woude G.F.V.
Oncogene 19:4947-4953(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GASTRIC CANCER SER-991, VARIANT ILE-992, CHARACTERIZATION OF VARIANT GASTRIC CANCER SER-991, CHARACTERIZATION OF VARIANT ILE-992.
[48]"A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer."
Kim I.-J., Park J.-H., Kang H.C., Shin Y., Lim S.-B., Ku J.-L., Yang H.-K., Lee K.U., Park J.-G.
J. Med. Genet. 40:E97-E97(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GASTRIC CANCER LEU-773.
[49]"The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway."
Wang D., Li Z., Messing E.M., Wu G.
J. Biol. Chem. 280:16393-16401(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPSB1; SPSB2; SPSB3 AND SPSB4.
[50]"A genetic variant that disrupts MET transcription is associated with autism."
Campbell D.B., Sutcliffe J.S., Ebert P.J., Militerni R., Bravaccio C., Trillo S., Elia M., Schneider C., Melmed R., Sacco R., Persico A.M., Levitt P.
Proc. Natl. Acad. Sci. U.S.A. 103:16834-16839(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO AUTS9, VARIANTS CYS-970 AND ILE-992.
[51]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-143; LEU-156; ASP-168; SER-375; CYS-970 AND ILE-992.
[52]"MET mutations in cancers of unknown primary origin (CUPs)."
Stella G.M., Benvenuti S., Gramaglia D., Scarpa A., Tomezzoli A., Cassoni P., Senetta R., Venesio T., Pozzi E., Bardelli A., Comoglio P.M.
Hum. Mutat. 32:44-50(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, CHARACTERIZATION OF VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, POSSIBLE INVOLVEMENT IN CUP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02958 mRNA. Translation: AAA59591.1.
X54559 mRNA. Translation: CAB56793.1.
EU826570 mRNA. Translation: ACF47606.1.
AC002080 Genomic DNA. Translation: AAB54047.1.
AC002543 Genomic DNA. Translation: AAC60383.1.
AC004416 Genomic DNA. Translation: AAF66137.2.
CH236947 Genomic DNA. Translation: EAL24359.1.
CH471070 Genomic DNA. Translation: EAW83509.1.
BC130420 mRNA. Translation: AAI30421.1.
U08818 mRNA. Translation: AAB60323.1. Sequence problems.
M35074 mRNA. Translation: AAA59590.1.
CCDSCCDS43636.1. [P08581-1]
CCDS47689.1. [P08581-2]
PIRTVHUME. A40175.
RefSeqNP_000236.2. NM_000245.2. [P08581-1]
NP_001120972.1. NM_001127500.1. [P08581-2]
UniGeneHs.132966.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FYRX-ray2.40I/J/K/L1356-1359[»]
1R0PX-ray1.80A1049-1360[»]
1R1WX-ray1.80A1049-1360[»]
1SHYX-ray3.22B25-567[»]
1SSLNMR-A519-562[»]
1UX3model-A25-656[»]
2G15X-ray2.15A1038-1346[»]
2RFNX-ray2.50A/B1048-1351[»]
2RFSX-ray2.20A1048-1351[»]
2UZXX-ray2.80B/D25-740[»]
2UZYX-ray4.00B/D25-740[»]
2WD1X-ray2.00A1055-1346[»]
2WGJX-ray2.00A1051-1348[»]
2WKMX-ray2.20A1051-1348[»]
3A4PX-ray2.54A1049-1360[»]
3BUXX-ray1.35A/C997-1009[»]
3C1XX-ray2.17A1049-1360[»]
3CCNX-ray1.90A1048-1350[»]
3CD8X-ray2.00A1048-1350[»]
3CE3X-ray2.40A1049-1360[»]
3CTHX-ray2.30A1049-1360[»]
3CTJX-ray2.50A1049-1360[»]
3DKCX-ray1.52A1049-1360[»]
3DKFX-ray1.80A1049-1360[»]
3DKGX-ray1.91A1049-1360[»]
3EFJX-ray2.60A/B1048-1351[»]
3EFKX-ray2.20A/B1048-1351[»]
3F66X-ray1.40A/B1052-1349[»]
3F82X-ray2.50A1049-1360[»]
3I5NX-ray2.00A1048-1350[»]
3L8VX-ray2.40A1049-1360[»]
3LQ8X-ray2.02A1051-1348[»]
3Q6UX-ray1.60A1048-1348[»]
3Q6WX-ray1.75A1048-1348[»]
3QTIX-ray2.00A/B1050-1360[»]
3R7OX-ray2.30A1048-1348[»]
3RHKX-ray1.94A/B1038-1346[»]
3U6HX-ray2.00A1048-1351[»]
3U6IX-ray2.10A1048-1351[»]
3VW8X-ray2.10A1024-1352[»]
3ZBXX-ray2.20A1051-1348[»]
3ZC5X-ray2.20A1051-1348[»]
3ZCLX-ray1.40A1051-1348[»]
3ZXZX-ray1.80A1051-1348[»]
3ZZEX-ray1.87A1051-1348[»]
4AOIX-ray1.90A1051-1348[»]
4AP7X-ray1.80A1051-1348[»]
4DEGX-ray2.00A1048-1351[»]
4DEHX-ray2.00A1048-1351[»]
4DEIX-ray2.05A1048-1351[»]
4EEVX-ray1.80A1038-1346[»]
4GG5X-ray2.42A1038-1346[»]
4GG7X-ray2.27A1038-1346[»]
4IWDX-ray1.99A1048-1348[»]
4K3JX-ray2.80B39-564[»]
4KNBX-ray2.40A/B/C/D1060-1346[»]
DisProtDP00317.
ProteinModelPortalP08581.
SMRP08581. Positions 40-741, 1024-1352.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110391. 32 interactions.
DIPDIP-6023N.
IntActP08581. 83 interactions.
MINTMINT-4837114.
STRING9606.ENSP00000317272.

Chemistry

BindingDBP08581.
ChEMBLCHEMBL3717.
GuidetoPHARMACOLOGY1815.

PTM databases

PhosphoSiteP08581.

Polymorphism databases

DMDM251757497.

2D gel databases

OGPP08581.

Proteomic databases

MaxQBP08581.
PaxDbP08581.
PRIDEP08581.

Protocols and materials databases

DNASU4233.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000318493; ENSP00000317272; ENSG00000105976. [P08581-2]
ENST00000397752; ENSP00000380860; ENSG00000105976. [P08581-1]
ENST00000436117; ENSP00000410980; ENSG00000105976. [P08581-3]
GeneID4233.
KEGGhsa:4233.
UCSCuc003vij.3. human. [P08581-1]
uc010lkh.3. human. [P08581-2]
uc011knc.1. human. [P08581-3]

Organism-specific databases

CTD4233.
GeneCardsGC07P116312.
HGNCHGNC:7029. MET.
HPACAB005282.
CAB018577.
HPA055607.
MIM114550. phenotype.
164860. gene.
605074. phenotype.
neXtProtNX_P08581.
Orphanet106. Autism.
47044. Familial papillary renal cell carcinoma.
33402. Hepatocellular carcinoma, childhood-onset.
PharmGKBPA30763.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000220900.
HOVERGENHBG006348.
KOK05099.
OMAQRVDLFM.
OrthoDBEOG7J70DR.
PhylomeDBP08581.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111045. Developmental Biology.
SignaLinkP08581.

Gene expression databases

ArrayExpressP08581.
BgeeP08581.
CleanExHS_MET.
GenevestigatorP08581.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR011009. Kinase-like_dom.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semap_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016244. Tyr_kinase_HGF/MSP_rcpt.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMET. human.
EvolutionaryTraceP08581.
GeneWikiC-Met.
GenomeRNAi4233.
NextBio16689.
PROP08581.
SOURCESearch...

Entry information

Entry nameMET_HUMAN
AccessionPrimary (citable) accession number: P08581
Secondary accession number(s): A1L467 expand/collapse secondary AC list , B5A932, E7EQ94, O60366, Q12875, Q9UDX7, Q9UPL8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: July 7, 2009
Last modified: July 9, 2014
This is version 197 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM