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Reviewed, UniProtKB/Swiss-Prot P16056 (MET_MOUSE)

Last modified December 15, 2009. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Hepatocyte growth factor receptor
      Short name=HGF receptor
    EC=2.7.10.1
Alternative name(s):
    Scatter factor receptor
      Short name=SF receptor
    HGF/SF receptor
    Met proto-oncogene tyrosine kinase
    c-Met
Gene names
Name: Met
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length1379 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity. Functions in cell proliferation, scattering, morphogenesis and survival By similarity.

Catalytic activity

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

Subunit structure

Heterodimer formed of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked By similarity. Binds PLXNB1 and GRB2 By similarity. When phosphorylated at Tyr-1354, interacts with INPPL1/SHIP2 By similarity. Interacts with RANBP9 and RANBP10 By similarity. Interacts with INPP5D/SHIP1. Interacts with SPSB1, SPSB2, SPSB4 and probably SPSB3. 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.

Subcellular location

Membrane; Single-pass type I membrane protein.

Domain

The kinase domain is involved in SPSB1 binding By similarity.

Involvement in disease

Activation of Met after rearrangement with the TPR (translocated promoter) locus of chromosome 1 produces an oncogenic protein.

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.

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Ontologies

Keywords
   Cellular componentMembrane
   DiseaseProto-oncogene
   DomainRepeat
Signal
Transmembrane
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Gene Ontology (GO)
   Biological processactivation of MAPK activity Ref.5

Inferred from physical interaction. Source: MGI

adult behavior

Inferred from mutant phenotype. Source: MGI

brain development

Inferred from mutant phenotype. Source: MGI

hepatocyte growth factor receptor signaling pathway Ref.5

Inferred from direct assay. Source: MGI

liver development

Inferred from mutant phenotype. Source: MGI

muscle cell migration

Inferred from mutant phenotype. Source: MGI

myoblast proliferation

Inferred from mutant phenotype. Source: MGI

myotube differentiation

Inferred from mutant phenotype. Source: MGI

placenta development

Inferred from mutant phenotype. Source: MGI

protein amino acid autophosphorylation Ref.5

Inferred from direct assay. Source: MGI

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

Inferred from mutant phenotype. Source: MGI

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane fraction

Inferred from direct assay. Source: MGI

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

hepatocyte growth factor receptor activity Ref.5

Inferred from direct assay. Source: MGI

protein binding

Inferred from physical interaction. Source: IntAct

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

HGFP142102EBI-1798780,EBI-1039104From a different organism.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 13791355Hepatocyte growth factor receptor
PRO_0000024441

Regions

Topological domain25 – 931907Extracellular Potential
Transmembrane932 – 95423 Potential
Topological domain955 – 1379425Cytoplasmic Potential
Domain27 – 514488Sema
Domain562 – 65493IPT/TIG 1
Domain656 – 73883IPT/TIG 2
Domain741 – 83595IPT/TIG 3
Domain1076 – 1343268Protein kinase
Nucleotide binding1082 – 10909ATP By similarity
Region1210 – 1379170Interaction with RANBP9 By similarity
Region1318 – 135740Interaction with MUC20 By similarity

Sites

Active site12021Proton acceptor By similarity
Binding site11081ATP By similarity
Site306 – 3072Cleavage Potential

Amino acid modifications

Modified residue9641Phosphoserine By similarity
Modified residue9751Phosphothreonine By similarity
Modified residue9861Phosphoserine By similarity
Modified residue9881Phosphoserine By similarity
Modified residue9951Phosphoserine By similarity
Modified residue9981Phosphoserine By similarity
Modified residue10011Phosphotyrosine By similarity
Modified residue12281Phosphotyrosine By similarity
Modified residue12321Phosphotyrosine By similarity
Modified residue12331Phosphotyrosine; by autocatalysis By similarity
Modified residue13541Phosphotyrosine By similarity
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation2011N-linked (GlcNAc...) Potential
Glycosylation3571N-linked (GlcNAc...) Potential
Glycosylation3981N-linked (GlcNAc...) Potential
Glycosylation4041N-linked (GlcNAc...) Potential
Glycosylation6061N-linked (GlcNAc...) Potential
Glycosylation6341N-linked (GlcNAc...) Potential
Glycosylation7841N-linked (GlcNAc...) Potential
Glycosylation8781N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict11991V → I in AAA40015. Ref.2
Sequence conflict12551T → R in AAA40015. Ref.2
Sequence conflict12611K → T in AAA40015. Ref.2
Sequence conflict1269 – 12702VL → IP Ref.2

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Sequences

Sequence LengthMass (Da)Tools
P16056-1 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: FC5CC87FDD8ADED8

FASTA1,379153,549
        10         20         30         40         50         60 
MKAPTVLAPG ILVLLLSLVQ RSHGECKEAL VKSEMNVNMK YQLPNFTAET PIQNVVLHGH 

        70         80         90        100        110        120 
HIYLGATNYI YVLNDKDLQK VSEFKTGPVL EHPDCLPCRD CSSKANSSGG VWKDNINMAL 

       130        140        150        160        170        180 
LVDTYYDDQL ISCGSVNRGT CQRHVLPPDN SADIQSEVHC MFSPEEESGQ CPDCVVSALG 

       190        200        210        220        230        240 
AKVLLSEKDR FINFFVGNTI NSSYPPGYSL HSISVRRLKE TQDGFKFLTD QSYIDVLPEF 

       250        260        270        280        290        300 
LDSYPIKYIH AFESNHFIYF LTVQKETLDA QTFHTRIIRF CSVDSGLHSY MEMPLECILT 

       310        320        330        340        350        360 
EKRRKRSTRE EVFNILQAAY VSKPGANLAK QIGASPSDDI LFGVFAQSKP DSAEPVNRSA 

       370        380        390        400        410        420 
VCAFPIKYVN DFFNKIVNKN NVRCLQHFYG PNHEHCFNRT LLRNSSGCEA RSDEYRTEFT 

       430        440        450        460        470        480 
TALQRVDLFM GRLNQVLLTS ISTFIKGDLT IANLGTSEGR FMQVVLSRTA HLTPHVNFLL 

       490        500        510        520        530        540 
DSHPVSPEVI VEHPSNQNGY TLVVTGKKIT KIPLNGLGCG HFQSCSQCLS APYFIQCGWC 

       550        560        570        580        590        600 
HNQCVRFDEC PSGTWTQEIC LPAVYKVFPT SAPLEGGTVL TICGWDFGFR KNNKFDLRKT 

       610        620        630        640        650        660 
KVLLGNESCT LTLSESTTNT LKCTVGPAMS EHFNVSVIIS NSRETTQYSA FSYVDPVITS 

       670        680        690        700        710        720 
ISPRYGPQAG GTLLTLTGKY LNSGNSRHIS IGGKTCTLKS VSDSILECYT PAQTTSDEFP 

       730        740        750        760        770        780 
VKLKIDLANR ETSSFSYRED PVVYEIHPTK SFISGGSTIT GIGKTLNSVS LPKLVIDVHE 

       790        800        810        820        830        840 
VGVNYTVACQ HRSNSEIICC TTPSLKQLGL QLPLKTKAFF LLDGILSKHF DLTYVHNPVF 

       850        860        870        880        890        900 
EPFEKPVMIS MGNENVVEIK GNNIDPEAVK GEVLKVGNQS CESLHWHSGA VLCTVPSDLL 

       910        920        930        940        950        960 
KLNSELNIEW KQAVSSTVLG KVIVQPDQNF AGLIIGAVSI SVVVLLLSGL FLWMRKRKHK 

       970        980        990       1000       1010       1020 
DLGSELVRYD ARVHTPHLDR LVSARSVSPT TEMVSNESVD YRATFPEDQF PNSSQNGACR 

      1030       1040       1050       1060       1070       1080 
QVQYPLTDLS PILTSGDSDI SSPLLQNTVH IDLSALNPEL VQAVQHVVIG PSSLIVHFNE 

      1090       1100       1110       1120       1130       1140 
VIGRGHFGCV YHGTLLDNDG KKIHCAVKSL NRITDIEEVS QFLTEGIIMK DFSHPNVLSL 

      1150       1160       1170       1180       1190       1200 
LGICLRSEGS PLVVLPYMKH GDLRNFIRNE THNPTVKDLI GFGLQVAKGM KYLASKKFVH 

      1210       1220       1230       1240       1250       1260 
RDLAARNCML DEKFTVKVAD FGLARDMYDK EYYSVHNKTG AKLPVKWMAL ESLQTQKFTT 

      1270       1280       1290       1300       1310       1320 
KSDVWSFGVL LWELMTRGAP PYPDVNTFDI TIYLLQGRRL LQPEYCPDAL YEVMLKCWHP 

      1330       1340       1350       1360       1370 
KAEMRPSFSE LVSRISSIFS TFIGEHYVHV NATYVNVKCV APYPSLLPSQ DNIDGEGNT

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References

[1]"Characterization of the mouse met proto-oncogene."
Chan A.M.-L., King H.W.S., Deakin E.A., Tempest P.R., Hilkens J., Kroezen V., Edwards D.R., Wills A.J., Brookes P., Cooper C.S.
Oncogene 2:593-599(1988) [PubMed: 2838789] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family."
Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.
Gene 85:67-74(1989) [PubMed: 2482828] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1199-1270.
[3]"The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells."
Weidner K.M., Sachs M., Birchmeier W.
J. Cell Biol. 121:145-154(1993) [PubMed: 8384622] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 924-935.
[4]"The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the control of cell-cell junction and induces dissociation and dispersion of MDCK cells."
Mancini A., Koch A., Wilms R., Tamura T.
Oncogene 21:1477-1484(2002) [PubMed: 11896575] [Abstract]
Cited for: INTERACTION WITH INPP5D.
[5]"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: 15314156] [Abstract]
Cited for: INTERACTION WITH MUC20.
[6]"The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues."
Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J., Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.
Nat. Struct. Mol. Biol. 13:77-84(2006) [PubMed: 16369487] [Abstract]
Cited for: INTERACTION WITH SPSB1; SPSB2 AND SPSB4.
+Additional computationally mapped references.

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Cross-references

Sequence databases

Y00671 mRNA. Translation: CAA68680.1.
M33424 mRNA. Translation: AAA40015.1.
IPIIPI00130420.
PIRS01254.
UniGeneMm.86844

3D structure databases

SMRP16056. Positions 40-563, 1044-1344.
ModBaseSearch...

Protein-protein interaction databases

IntActP16056. 1 interaction.
STRINGP16056.

PTM databases

PhosphoSiteP16056.

Proteomic databases

PRIDEP16056.

Genome annotation databases

EnsemblENSMUST00000080469; ENSMUSP00000079324; ENSMUSG00000009376; Mus musculus. [Genome view]
ENSMUST00000115442; ENSMUSP00000111102; ENSMUSG00000009376; Mus musculus. [Genome view]
ENSMUST00000115443; ENSMUSP00000111103; ENSMUSG00000009376; Mus musculus. [Genome view]
UCSCuc009azr.1. mouse.

Organism-specific databases

MGIMGI:96969. Met.

Phylogenomic databases

HOGENOMHBG445765.
HOVERGENP16056.
InParanoidP16056.

Enzyme and pathway databases

BRENDA2.7.10.1. 244.

Gene expression databases

ArrayExpressP16056.
BgeeP16056.
CleanExMM_MET.
GenevestigatorP16056.
GermOnlineENSMUSG00000009376. Mus musculus.

Family and domain databases

InterProIPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR011009. Kinase-like_dom.
IPR003659. Plexin-like.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semaphorin/CD100_Ag.
IPR020707. Tyr_kinase_hepatocyte_GF_rcpt.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR001245. Tyr_prot_kinase_cat_dom.
IPR016244. Tyr_prot_kinase_HGF/MSP_rcpt.
IPR020635. Tyr_prot_kinase_subgr_cat_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
Gene3DG3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
PANTHERPTHR23256:SF169. Tyr_kinase_hepatocyte_GF_rcpt. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.
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.
SMARTSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
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 Resources

PMAP-CutDBP16056.
SOURCESearch...

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Entry information

Entry nameMET_MOUSE
AccessionPrimary (citable) accession number: P16056
Secondary accession number(s): Q62125
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: December 15, 2009
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents