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P16056

- MET_MOUSE

UniProt

P16056 - MET_MOUSE

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Protein
Hepatocyte growth factor receptor
Gene
Met
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 By similarity.1 Publication

Catalytic activityi

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

Enzyme regulationi

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 By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei306 – 3072Cleavage Reviewed prediction
Binding sitei1108 – 11081ATP By similarity
Active sitei1202 – 12021Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1082 – 10909ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. hepatocyte growth factor-activated receptor activity Source: MGI
  3. protein binding Source: IntAct
  4. protein kinase activity Source: MGI
Complete GO annotation...

GO - Biological processi

  1. activation of MAPK activity Source: MGI
  2. adult behavior Source: MGI
  3. brain development Source: MGI
  4. glucose homeostasis Source: MGI
  5. hepatocyte growth factor receptor signaling pathway Source: MGI
  6. liver development Source: MGI
  7. muscle cell migration Source: MGI
  8. muscle organ development Source: MGI
  9. myoblast proliferation Source: MGI
  10. myotube differentiation Source: MGI
  11. placenta development Source: MGI
  12. positive chemotaxis Source: UniProtKB
  13. positive regulation of endothelial cell chemotaxis Source: UniProtKB
  14. positive regulation of glucose transport Source: MGI
  15. protein autophosphorylation Source: MGI
  16. regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Source: MGI
  17. regulation of excitatory postsynaptic membrane potential Source: BHF-UCL
  18. regulation of synaptic transmission Source: BHF-UCL
  19. semaphorin-plexin signaling pathway Source: UniProtKB
  20. skeletal muscle tissue development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor receptor (EC:2.7.10.1)
Short name:
HGF receptor
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name:
SF receptor
Tyrosine-protein kinase Met
Gene namesi
Name:Met
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:96969. Met.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 931907Extracellular Reviewed prediction
Add
BLAST
Transmembranei932 – 95423Helical; Reviewed prediction
Add
BLAST
Topological domaini955 – 1379425Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. basal plasma membrane Source: MGI
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424 Reviewed prediction
Add
BLAST
Chaini25 – 13791355Hepatocyte growth factor receptor
PRO_0000024441Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi45 – 451N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi95 ↔ 101 By similarity
Disulfide bondi98 ↔ 160 By similarity
Glycosylationi106 – 1061N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi133 ↔ 141 By similarity
Disulfide bondi171 ↔ 174 By similarity
Glycosylationi201 – 2011N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi297 ↔ 362 By similarity
Glycosylationi357 – 3571N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi384 ↔ 396 By similarity
Glycosylationi398 – 3981N-linked (GlcNAc...) Reviewed prediction
Glycosylationi404 – 4041N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi519 ↔ 537 By similarity
Disulfide bondi525 ↔ 560 By similarity
Disulfide bondi528 ↔ 544 By similarity
Disulfide bondi540 ↔ 550 By similarity
Glycosylationi606 – 6061N-linked (GlcNAc...) Reviewed prediction
Glycosylationi634 – 6341N-linked (GlcNAc...) Reviewed prediction
Glycosylationi784 – 7841N-linked (GlcNAc...) Reviewed prediction
Glycosylationi878 – 8781N-linked (GlcNAc...) Reviewed prediction
Modified residuei975 – 9751Phosphothreonine By similarity
Modified residuei988 – 9881Phosphoserine By similarity
Modified residuei995 – 9951Phosphoserine By similarity
Modified residuei998 – 9981Phosphoserine By similarity
Modified residuei1001 – 10011Phosphotyrosine By similarity
Modified residuei1228 – 12281Phosphotyrosine By similarity
Modified residuei1232 – 12321Phosphotyrosine; by autocatalysis By similarity
Modified residuei1233 – 12331Phosphotyrosine; by autocatalysis By similarity
Modified residuei1287 – 12871Phosphothreonine By similarity
Modified residuei1347 – 13471Phosphotyrosine; by autocatalysis By similarity
Modified residuei1354 – 13541Phosphotyrosine; by autocatalysis By similarity
Modified residuei1363 – 13631Phosphotyrosine By similarity

Post-translational modificationi

Autophosphorylated in response to ligand binding on Tyr-1232 and Tyr-1233 in the kinase domain leading to further phosphorylation of Tyr-1347 and Tyr-1354 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1347 and Tyr-1363 By similarity. Dephosphorylated by PTPN1 and PTPN2 By similarity.
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP16056.
PaxDbiP16056.
PRIDEiP16056.

PTM databases

PhosphoSiteiP16056.

Miscellaneous databases

PMAP-CutDBP16056.

Expressioni

Gene expression databases

CleanExiMM_MET.
GenevestigatoriP16056.

Interactioni

Subunit structurei

Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked By similarity. Binds PLXNB1 By similarity. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1 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. Interacts with GRB10 By similarity. Interacts with PTPN1 and PTPN2 By similarity.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CblP226822EBI-1798780,EBI-640919
HGFP142102EBI-1798780,EBI-1039104From a different organism.
KdrP359183EBI-1798780,EBI-1555005

Protein-protein interaction databases

IntActiP16056. 4 interactions.
MINTiMINT-137318.

Structurei

3D structure databases

ProteinModelPortaliP16056.
SMRiP16056. Positions 40-740, 1022-1376.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 514488Sema
Add
BLAST
Domaini562 – 65493IPT/TIG 1
Add
BLAST
Domaini656 – 73883IPT/TIG 2
Add
BLAST
Domaini741 – 83595IPT/TIG 3
Add
BLAST
Domaini1076 – 1343268Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1210 – 1379170Interaction with RANBP9 By similarity
Add
BLAST
Regioni1318 – 135740Interaction with MUC20 By similarity
Add
BLAST

Domaini

The kinase domain is involved in SPSB1 binding By similarity.
The beta-propeller Sema domain mediates binding to HGF By similarity.

Sequence similaritiesi

Contains 3 IPT/TIG domains.
Contains 1 Sema domain.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiP16056.
PhylomeDBiP16056.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProiIPR013783. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFiPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16056-1 [UniParc]FASTAAdd to Basket

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MKAPTVLAPG ILVLLLSLVQ RSHGECKEAL VKSEMNVNMK YQLPNFTAET     50
PIQNVVLHGH HIYLGATNYI YVLNDKDLQK VSEFKTGPVL EHPDCLPCRD 100
CSSKANSSGG VWKDNINMAL LVDTYYDDQL ISCGSVNRGT CQRHVLPPDN 150
SADIQSEVHC MFSPEEESGQ CPDCVVSALG AKVLLSEKDR FINFFVGNTI 200
NSSYPPGYSL HSISVRRLKE TQDGFKFLTD QSYIDVLPEF LDSYPIKYIH 250
AFESNHFIYF LTVQKETLDA QTFHTRIIRF CSVDSGLHSY MEMPLECILT 300
EKRRKRSTRE EVFNILQAAY VSKPGANLAK QIGASPSDDI LFGVFAQSKP 350
DSAEPVNRSA VCAFPIKYVN DFFNKIVNKN NVRCLQHFYG PNHEHCFNRT 400
LLRNSSGCEA RSDEYRTEFT TALQRVDLFM GRLNQVLLTS ISTFIKGDLT 450
IANLGTSEGR FMQVVLSRTA HLTPHVNFLL DSHPVSPEVI VEHPSNQNGY 500
TLVVTGKKIT KIPLNGLGCG HFQSCSQCLS APYFIQCGWC HNQCVRFDEC 550
PSGTWTQEIC LPAVYKVFPT SAPLEGGTVL TICGWDFGFR KNNKFDLRKT 600
KVLLGNESCT LTLSESTTNT LKCTVGPAMS EHFNVSVIIS NSRETTQYSA 650
FSYVDPVITS ISPRYGPQAG GTLLTLTGKY LNSGNSRHIS IGGKTCTLKS 700
VSDSILECYT PAQTTSDEFP VKLKIDLANR ETSSFSYRED PVVYEIHPTK 750
SFISGGSTIT GIGKTLNSVS LPKLVIDVHE VGVNYTVACQ HRSNSEIICC 800
TTPSLKQLGL QLPLKTKAFF LLDGILSKHF DLTYVHNPVF EPFEKPVMIS 850
MGNENVVEIK GNNIDPEAVK GEVLKVGNQS CESLHWHSGA VLCTVPSDLL 900
KLNSELNIEW KQAVSSTVLG KVIVQPDQNF AGLIIGAVSI SVVVLLLSGL 950
FLWMRKRKHK DLGSELVRYD ARVHTPHLDR LVSARSVSPT TEMVSNESVD 1000
YRATFPEDQF PNSSQNGACR QVQYPLTDLS PILTSGDSDI SSPLLQNTVH 1050
IDLSALNPEL VQAVQHVVIG PSSLIVHFNE VIGRGHFGCV YHGTLLDNDG 1100
KKIHCAVKSL NRITDIEEVS QFLTEGIIMK DFSHPNVLSL LGICLRSEGS 1150
PLVVLPYMKH GDLRNFIRNE THNPTVKDLI GFGLQVAKGM KYLASKKFVH 1200
RDLAARNCML DEKFTVKVAD FGLARDMYDK EYYSVHNKTG AKLPVKWMAL 1250
ESLQTQKFTT KSDVWSFGVL LWELMTRGAP PYPDVNTFDI TIYLLQGRRL 1300
LQPEYCPDAL YEVMLKCWHP KAEMRPSFSE LVSRISSIFS TFIGEHYVHV 1350
NATYVNVKCV APYPSLLPSQ DNIDGEGNT 1379
Length:1,379
Mass (Da):153,549
Last modified:April 1, 1990 - v1
Checksum:iFC5CC87FDD8ADED8
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1199 – 11991V → I in AAA40015. 1 Publication
Sequence conflicti1255 – 12551T → R in AAA40015. 1 Publication
Sequence conflicti1261 – 12611K → T in AAA40015. 1 Publication
Sequence conflicti1269 – 12702VL → IP1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00671 mRNA. Translation: CAA68680.1.
M33424 mRNA. Translation: AAA40015.1.
CCDSiCCDS19925.1.
PIRiS01254.
UniGeneiMm.86844.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00671 mRNA. Translation: CAA68680.1 .
M33424 mRNA. Translation: AAA40015.1 .
CCDSi CCDS19925.1.
PIRi S01254.
UniGenei Mm.86844.

3D structure databases

ProteinModelPortali P16056.
SMRi P16056. Positions 40-740, 1022-1376.
ModBasei Search...

Protein-protein interaction databases

IntActi P16056. 4 interactions.
MINTi MINT-137318.

Chemistry

ChEMBLi CHEMBL5585.

PTM databases

PhosphoSitei P16056.

Proteomic databases

MaxQBi P16056.
PaxDbi P16056.
PRIDEi P16056.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

MGIi MGI:96969. Met.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000220900.
HOVERGENi HBG006348.
InParanoidi P16056.
PhylomeDBi P16056.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.

Miscellaneous databases

ChiTaRSi MET. mouse.
PMAP-CutDB P16056.
PROi P16056.
SOURCEi Search...

Gene expression databases

CleanExi MM_MET.
Genevestigatori P16056.

Family and domain databases

Gene3Di 2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProi IPR013783. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view ]
PIRSFi PIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 924-935.
  4. "Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud."
    Bladt F., Riethmacher D., Isenmann S., Aguzzi A., Birchmeier C.
    Nature 376:768-771(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEVELOPMENT.
  5. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INPP5D.
  6. "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: INTERACTION WITH MUC20.
  7. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SPSB1; SPSB2 AND SPSB4.

Entry informationi

Entry nameiMET_MOUSE
AccessioniPrimary (citable) accession number: P16056
Secondary accession number(s): Q62125
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi