Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)

 MET_ATEAB               Reviewed;        1382 AA.
 Q00PJ8;
 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
 14-NOV-2006, sequence version 1.
 25-MAY-2022, entry version 80.
 RecName: Full=Hepatocyte growth factor receptor;
          Short=HGF receptor;
          EC=2.7.10.1;
 AltName: Full=HGF/SF receptor;
 AltName: Full=Proto-oncogene c-Met;
 AltName: Full=Scatter factor receptor;
          Short=SF receptor;
 AltName: Full=Tyrosine-protein kinase Met;
 Flags: Precursor;
 Name=MET;
 Atelerix albiventris (Middle-African hedgehog) (Four-toed hedgehog).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Laurasiatheria; Eulipotyphla; Erinaceidae; Erinaceinae; Atelerix.
 NCBI_TaxID=9368;
 [1]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 Antonellis A., Ayele K., Benjamin B., Blakesley R.W., Boakye A.,
 Bouffard G.G., Brinkley C., Brooks S., Chu G., Coleman H., Engle J.,
 Gestole M., Greene A., Guan X., Gupta J., Haghighi P., Han J., Hansen N.,
 Ho S.-L., Hu P., Hunter G., Hurle B., Idol J.R., Kwong P., Laric P.,
 Larson S., Lee-Lin S.-Q., Legaspi R., Madden M., Maduro Q.L., Maduro V.B.,
 Margulies E.H., Masiello C., Maskeri B., McDowell J., Mojidi H.A.,
 Mullikin J.C., Oestreicher J.S., Park M., Portnoy M.E., Prasad A., Puri O.,
 Reddix-Dugue N., Schandler K., Schueler M.G., Sison C., Stantripop S.,
 Stephen E., Taye A., Thomas J.W., Thomas P.J., Tsipouri V., Ung L.,
 Vogt J.L., Wetherby K.D., Young A., Green E.D.;
 "NISC comparative sequencing initiative.";
 Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
 -!- 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
     (By similarity). {ECO:0000250}.
 -!- CATALYTIC ACTIVITY:
     Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
       [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
       COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
       ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
       Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
 -!- ACTIVITY 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 (By similarity).
     {ECO:0000250}.
 -!- SUBUNIT: 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. Interacts
     with INPP5D/SHIP1. When phosphorylated at Tyr-1357, 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 (By similarity). Interacts with PTPN1 and PTPN2
     (By similarity). {ECO:0000250}.
 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
     membrane protein {ECO:0000250}.
 -!- DOMAIN: The kinase domain is involved in SPSB1 binding. {ECO:0000250}.
 -!- DOMAIN: The beta-propeller Sema domain mediates binding to HGF.
     {ECO:0000250}.
 -!- PTM: Autophosphorylated in response to ligand binding on Tyr-1235 and
     Tyr-1236 in the kinase domain leading to further phosphorylation of
     Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site.
     Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by
     PTPN1 and PTPN2 (By similarity). {ECO:0000250}.
 -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
     stability and activity through proteasomal degradation (By similarity).
     {ECO:0000250}.
 -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
     kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
 ---------------------------------------------------------------------------
 Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
 Distributed under the Creative Commons Attribution (CC BY 4.0) License
 ---------------------------------------------------------------------------
 EMBL; DP000003; AAY88979.1; -; Genomic_DNA.
 AlphaFoldDB; Q00PJ8; -.
 SMR; Q00PJ8; -.
 PRIDE; Q00PJ8; -.
 GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
 GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA.
 GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro.
 GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:UniProtKB-EC.
 GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
 GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB.
 GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
 GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
 Gene3D; 2.130.10.10; -; 1.
 Gene3D; 2.60.40.10; -; 2.
 InterPro; IPR013783; Ig-like_fold.
 InterPro; IPR014756; Ig_E-set.
 InterPro; IPR002909; IPT_dom.
 InterPro; IPR011009; Kinase-like_dom_sf.
 InterPro; IPR031148; Plexin.
 InterPro; IPR002165; Plexin_repeat.
 InterPro; IPR000719; Prot_kinase_dom.
 InterPro; IPR017441; Protein_kinase_ATP_BS.
 InterPro; IPR016201; PSI.
 InterPro; IPR001627; Semap_dom.
 InterPro; IPR036352; Semap_dom_sf.
 InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 InterPro; IPR008266; Tyr_kinase_AS.
 InterPro; IPR020635; Tyr_kinase_cat_dom.
 InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt.
 InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
 PANTHER; PTHR22625; PTHR22625; 1.
 Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
 Pfam; PF01437; PSI; 1.
 Pfam; PF01403; Sema; 1.
 Pfam; PF01833; TIG; 3.
 PIRSF; PIRSF000617; TyrPK_HGF-R; 1.
 PRINTS; PR00109; TYRKINASE.
 SMART; SM00429; IPT; 4.
 SMART; SM00423; PSI; 1.
 SMART; SM00630; Sema; 1.
 SMART; SM00219; TyrKc; 1.
 SUPFAM; SSF101912; SSF101912; 1.
 SUPFAM; SSF56112; SSF56112; 1.
 SUPFAM; SSF81296; SSF81296; 3.
 PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
 PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
 PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
 PROSITE; PS51004; SEMA; 1.
 3: Inferred from homology;
 ATP-binding; Disulfide bond; Glycoprotein; Kinase; Membrane;
 Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor; Repeat;
 Signal; Transferase; Transmembrane; Transmembrane helix;
 Tyrosine-protein kinase; Ubl conjugation.
 SIGNAL          1..24
                 /evidence="ECO:0000255"
 CHAIN           25..1382
                 /note="Hepatocyte growth factor receptor"
                 /id="PRO_0000274185"
 TOPO_DOM        25..933
                 /note="Extracellular"
                 /evidence="ECO:0000255"
 TRANSMEM        934..956
                 /note="Helical"
                 /evidence="ECO:0000255"
 TOPO_DOM        957..1382
                 /note="Cytoplasmic"
                 /evidence="ECO:0000255"
 DOMAIN          27..516
                 /note="Sema"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DOMAIN          564..656
                 /note="IPT/TIG 1"
 DOMAIN          658..740
                 /note="IPT/TIG 2"
 DOMAIN          743..837
                 /note="IPT/TIG 3"
 DOMAIN          1079..1346
                 /note="Protein kinase"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
 NP_BIND         1085..1093
                 /note="ATP"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
 REGION          1213..1382
                 /note="Interaction with RANBP9"
                 /evidence="ECO:0000250"
 REGION          1321..1360
                 /note="Interaction with MUC20"
                 /evidence="ECO:0000250"
 ACT_SITE        1205
                 /note="Proton acceptor"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
                 ECO:0000255|PROSITE-ProRule:PRU10028"
 BINDING         1111
                 /note="ATP"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
 SITE            308..309
                 /note="Cleavage"
                 /evidence="ECO:0000255"
 MOD_RES         967
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         978
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         991
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         998
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1001
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1004
                 /note="Phosphotyrosine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1231
                 /note="Phosphotyrosine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1235
                 /note="Phosphotyrosine; by autocatalysis"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1236
                 /note="Phosphotyrosine; by autocatalysis"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1290
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1350
                 /note="Phosphotyrosine; by autocatalysis"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1357
                 /note="Phosphotyrosine; by autocatalysis"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 MOD_RES         1366
                 /note="Phosphotyrosine"
                 /evidence="ECO:0000250|UniProtKB:P08581"
 CARBOHYD        45
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        106
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        203
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        359
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        400
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        406
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        608
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        636
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        786
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        880
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        931
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 DISULFID        95..101
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        98..160
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        133..141
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        173..176
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        299..364
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        386..398
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        521..539
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        527..562
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        530..546
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 DISULFID        542..552
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
 SEQUENCE   1382 AA;  155029 MW;  C247A70F6D16C054 CRC64;
 MKASAVLAPG ILVILFTLVQ KSNCECKEAL VKSKMNVNMK YQLPNFTAET PIQNVVLHNH
 HIYLGAVNYI YVLSDKTLQK VAEYKTGPVL EHPDCLPCQD CRHKANLSNG IWKDNINMAL
 LVDTYYDDQL ISCGSVHRGT CQRHVLPPNN AADIQSEVHC MYTPQPEEEP SQCPDCVVSA
 LGTKVLLSEK NRFINFFVGN TINSSYLPDH SLHSMSVRRL KETQDGFKFL TDQSYIDVLP
 EFRDSYPIKY IHAFKSNHFI YFLTVQRETL DAQTFHTRII RFCSGDSGLH SYMEMPLECI
 LTEKRRKRAA REEVFNILQA AYVSKPGAHL ARQIGASLND DILYGVFAQS KPDSAEPMNR
 SAVCAFPIKY VNEFFNKIVN KNNVRCLQHF YGPNHEHCFN RTLLRNSSSC DVRSDEYRTE
 FTTALQRVDL FMGQFNQVLL TSISTFIKGD LTIANLGTSE GRFMQVVVSR LGSSTPHVNF
 RLDSHPVSPE VIVEHPLNGN DYTLVVTGKK ITKIPLNGLG CEHFQSCSQC LSAPAFVQCG
 WCHDKCVQLE ECPSGTWTQE TCLPTIYKVL PTSAPLEGGT TLTICGWDFG FRRNNKFDLK
 KTRVFLGNES CTVTLSESST NMLKCTVGPA LYEHFNMSII ISNSRGTVQY STFSYVDPII
 TSISPTYGPK TGGTLLTLTG KYLDSGNSRH ISIGGKTCTL KSVSNSILEC YTPPQTTSTE
 FPVKLKIDLA NRNTYSFSYQ EDPIIYKIHP IKSFISGGST ITGVGKNLNS VSVLRMVINV
 HEAGRNFTVA CQHRSNSEII CCTTPSLQQL DLQLPLTTRA FFMLDGIHSR YFDLIYVHNP
 MFKVFEKPVK ISIGIENILE IKGNDIDPEA VKGEVLKVGN KSCENIHSYS ETVLCTVPND
 LLKLNSELNI EWKQAVTSTV LGKVIVQPDQ NITEFIVGIL SISGILLTLL GLLLWWKKKK
 QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE SVDYRATFPE DQFPNSSQNG
 SCRQVQYPLT DLSPILTSGD SDISSPLLQN TVHIDLSALN PELVQAVQHV VIGPSSLIVH
 FNEVIGRGHF GCVYHGTLLD NDDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV
 LSLLGICLRS EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK
 FVHRDLAARN CMLDENFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW MALESLQTQK
 FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG RRLLQPEYCP DPLYEVMLKC
 WHPKAELRPS FSELVSRISA IFSTFIGEHY VHVNATYVNI KCVAPYPSLL SSQDNFDSEG
 NT

Related products :