MET_BOVIN
ID MET_BOVIN Reviewed; 1384 AA.
AC Q769I5; A4D7R6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Hepatocyte growth factor receptor;
DE Short=HGF receptor;
DE EC=2.7.10.1;
DE AltName: Full=HGF/SF receptor;
DE AltName: Full=Proto-oncogene c-Met;
DE AltName: Full=Scatter factor receptor;
DE Short=SF receptor;
DE AltName: Full=Tyrosine-protein kinase Met;
DE Flags: Precursor;
GN Name=MET;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=16207523; DOI=10.1016/j.domaniend.2005.08.005;
RA Yamaji D., Kimura K., Watanabe A., Kon Y., Iwanaga T., Soliman M.M.,
RA Ahmed M.M., Saito M.;
RT "Bovine hepatocyte growth factor and its receptor c-Met: cDNA cloning and
RT expression analysis in the mammary gland.";
RL Domest. Anim. Endocrinol. 30:239-246(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12917688; DOI=10.1038/nature01858;
RA Thomas J.W., Touchman J.W., Blakesley R.W., Bouffard G.G.,
RA Beckstrom-Sternberg S.M., Margulies E.H., Blanchette M., Siepel A.C.,
RA Thomas P.J., McDowell J.C., Maskeri B., Hansen N.F., Schwartz M.S.,
RA Weber R.J., Kent W.J., Karolchik D., Bruen T.C., Bevan R., Cutler D.J.,
RA Schwartz S., Elnitski L., Idol J.R., Prasad A.B., Lee-Lin S.-Q.,
RA Maduro V.V.B., Summers T.J., Portnoy M.E., Dietrich N.L., Akhter N.,
RA Ayele K., Benjamin B., Cariaga K., Brinkley C.P., Brooks S.Y., Granite S.,
RA Guan X., Gupta J., Haghighi P., Ho S.-L., Huang M.C., Karlins E.,
RA Laric P.L., Legaspi R., Lim M.J., Maduro Q.L., Masiello C.A.,
RA Mastrian S.D., McCloskey J.C., Pearson R., Stantripop S., Tiongson E.E.,
RA Tran J.T., Tsurgeon C., Vogt J.L., Walker M.A., Wetherby K.D.,
RA Wiggins L.S., Young A.C., Zhang L.-H., Osoegawa K., Zhu B., Zhao B.,
RA Shu C.L., De Jong P.J., Lawrence C.E., Smit A.F., Chakravarti A.,
RA Haussler D., Green P., Miller W., Green E.D.;
RT "Comparative analyses of multi-species sequences from targeted genomic
RT regions.";
RL Nature 424:788-793(2003).
CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the
CC extracellular matrix into the cytoplasm by binding to hepatocyte growth
CC factor/HGF ligand. Regulates many physiological processes including
CC proliferation, scattering, morphogenesis and survival. Ligand binding
CC at the cell surface induces autophosphorylation of MET on its
CC intracellular domain that provides docking sites for downstream
CC signaling molecules. Following activation by ligand, interacts with the
CC PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1.
CC Recruitment of these downstream effectors by MET leads to the
CC activation of several signaling cascades including the RAS-ERK, PI3
CC kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with
CC the morphogenetic effects while PI3K/AKT coordinates prosurvival
CC effects. During embryonic development, MET signaling plays a role in
CC gastrulation, development and migration of muscles and neuronal
CC precursors, angiogenesis and kidney formation. In adults, participates
CC in wound healing as well as organ regeneration and tissue remodeling.
CC Promotes also differentiation and proliferation of hematopoietic cells
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: In its inactive state, the C-terminal tail
CC interacts with the catalytic domain and inhibits the kinase activity.
CC Upon ligand binding, the C-terminal tail is displaced and becomes
CC phosphorylated, thus increasing the kinase activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer made of an alpha chain (50 kDa) and a beta chain
CC (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when
CC phosphorylated with downstream effectors including STAT3, PIK3R1, SRC,
CC PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts
CC with INPP5D/SHIP1. When phosphorylated at Tyr-1357, interacts with
CC INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1,
CC SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the
CC absence of HGF, however HGF treatment has a positive effect on this
CC interaction. Interacts with MUC20; prevents interaction with GRB2 and
CC suppresses hepatocyte growth factor-induced cell proliferation.
CC Interacts with GRB10. Interacts with PTPN1 and PTPN2. Interacts with
CC HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity.
CC {ECO:0000250|UniProtKB:P08581, ECO:0000250|UniProtKB:P16056}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:16207523}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:16207523}.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, including liver, lung,
CC heart, spleen and mammary gland. {ECO:0000269|PubMed:16207523}.
CC -!- DEVELOPMENTAL STAGE: In the mammary gland, at the mRNA level, expressed
CC in the inactive and involuting stages, but not in the developing, nor
CC lactating stages. However, at the protein level, detected on epithelial
CC cells in the inactive, developing and involuting stages, but not in the
CC lactating stage, and at all stages on myoepithelial cells, while it is
CC not found on adipocytes and fibroblasts. {ECO:0000269|PubMed:16207523}.
CC -!- DOMAIN: The kinase domain is involved in SPSB1 binding. {ECO:0000250}.
CC -!- DOMAIN: The beta-propeller Sema domain mediates binding to HGF.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated in response to ligand binding on Tyr-1235 and
CC Tyr-1236 in the kinase domain leading to further phosphorylation of
CC Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site.
CC Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by
CC PTPN1 and PTPN2 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
CC stability and activity through proteasomal degradation (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB112434; BAD05055.1; -; mRNA.
DR EMBL; DP000008; AAR16257.1; -; Genomic_DNA.
DR RefSeq; NP_001013017.2; NM_001012999.2.
DR AlphaFoldDB; Q769I5; -.
DR SMR; Q769I5; -.
DR STRING; 9913.ENSBTAP00000008102; -.
DR PaxDb; Q769I5; -.
DR PRIDE; Q769I5; -.
DR GeneID; 280855; -.
DR KEGG; bta:280855; -.
DR CTD; 4233; -.
DR eggNOG; KOG1095; Eukaryota.
DR eggNOG; KOG3610; Eukaryota.
DR InParanoid; Q769I5; -.
DR OrthoDB; 408584at2759; -.
DR TreeFam; TF317402; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005008; F:hepatocyte growth factor receptor activity; IBA:GO_Central.
DR GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0001889; P:liver development; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0031016; P:pancreas development; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR031148; Plexin.
DR InterPro; IPR002165; Plexin_repeat.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016201; PSI.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR036352; Semap_dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PANTHER; PTHR22625; PTHR22625; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR Pfam; PF01833; TIG; 3.
DR PIRSF; PIRSF000617; TyrPK_HGF-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00429; IPT; 4.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF81296; SSF81296; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1384
FT /note="Hepatocyte growth factor receptor"
FT /id="PRO_0000274195"
FT TOPO_DOM 25..933
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 934..956
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 957..1384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..516
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 564..656
FT /note="IPT/TIG 1"
FT DOMAIN 658..740
FT /note="IPT/TIG 2"
FT DOMAIN 743..837
FT /note="IPT/TIG 3"
FT DOMAIN 1079..1346
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1213..1382
FT /note="Interaction with RANBP9"
FT /evidence="ECO:0000250"
FT REGION 1321..1360
FT /note="Interaction with MUC20"
FT /evidence="ECO:0000250"
FT ACT_SITE 1205
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1085..1093
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 308..309
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 978
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 998
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1001
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1004
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1231
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1235
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1236
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1290
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1350
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1357
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT MOD_RES 1366
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08581"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 608
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 636
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 786
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 880
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 931
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 95..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 98..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 133..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 173..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 299..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 386..398
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 521..539
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 527..562
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 530..546
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 542..552
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT CONFLICT 1052
FT /note="I -> V (in Ref. 2; AAR16257)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1384 AA; 154814 MW; 3DCCC95949264A26 CRC64;
MKAPAVLAPG ILVLLFTFVQ KSNGECKEAL VKSRMNVNMQ YQLPNFTAET SIQNVVLHKH
HIYLGAINYI YVLNDKDLQK VAEYKTGPVL EHPDCFPCQD CSHKANLSGG VWKDNINMAL
LVDTYYDDQL ISCGSVHRGT CQRHVLPPNN TADIESEVHC MYSPQADEET NQCPDCVVSA
LGTKVLLSEK DRFINFFVGN TINSSYLPDY ILHSISVRRL KETQDGFKFL TDQSYIDVLP
ELRDSYPIKY VHAFESNHFI YFLTVQRETL DAQTFHTRII RFCSADSGLH SYMEMPLECI
LTEKRRKRST KQEVFNILQA AYVSKPGAQL ARQIGASLND DILYGVFAQS KPDSSEPMNR
SAVCAFPVKY VNEFFNKIVN KNNVRCLQHF YGPNHEHCFN RTLLRNSSGC EVRNDEYRTE
FTTALPRVDL FTGQFNQVLL TSISTFIKGD LTIANLGTSE GRFMQVVVSR SGSLTPHVNF
HLDSHPVSPE VIVEHPLNQN GYTLVVTGKK ITKIPLNGLG CEHFQSCSQC LSAPSFVQCG
WCHDKCVRLE ECSSGTWTQE TCLPTIYKVF PTSAPLEGGT TLTVCGWDFG FKRNNKFDLK
KTRVLLGNES CTLTLTESTT NMLKCTVGPA MNEHFNMSIV ISNSRGSVEY SAFSYVDPII
TSISPNYGPK TGGTLLTLTG KHLNSGNSRH ISIGGKTCTL KSVSHSILEC YTPAQSAPTE
FSVKLKIDLA NREVNSFIYR EDPIVYEIHP TKSFISGGST ITGVGKNLNS VSVLRMVINV
HEAGRNFTVA CQHRSNSEII CCTTPSIEQL NLQLPLKTKA FFMLDGIHSK YFDLIYVHNP
VFKPFEKPVM ISVGNENVLE IKGNDIDPEA VKGEVLKVGN KSCENIHSHS EAVLCTVPSD
LLKLNSELNI EWKQAISSTV LGKVIVQPDQ NFTGLIVGVV SISIILLLLL GLFLWLKKRK
QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE SVDYRATFPE DQFPNASQNG
SCRQVQYPLT DLSPILTSGD SDISSPLLQN TIHIDLSALN PELVQAVQHV VIGPSSLIVH
FNEVIGRGHF GCVYHGTLLD NDDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV
LSLLGICLRS EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMEYLASKK
FVHRDLAARN CMLDEKFTVK VADFGLARDV YDKEYYSVHN KTGAKLPVKW MALESLQTQK
FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG RRLLQPEYCP DPLYEVMLKC
WHPKAELRPS FSELVSRISV IFSTFIGEHY VHVNATYVNV KCVAPYPSLL SSQDNVSGED
DDDT
