MET_MUSPF
ID MET_MUSPF Reviewed; 1382 AA.
AC Q07E24;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 90.
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 Mustela putorius furo (European domestic ferret) (Mustela furo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Mustelidae; Mustelinae;
OC Mustela.
OX NCBI_TaxID=9669;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Antonellis A., Ayele K., Benjamin B., Blakesley R.W., Boakye A.,
RA Bouffard G.G., Brinkley C., Brooks S., Chu G., Coleman H., Engle J.,
RA Gestole M., Greene A., Guan X., Gupta J., Haghighi P., Han J., Hansen N.,
RA Ho S.-L., Hu P., Hunter G., Hurle B., Idol J.R., Kwong P., Laric P.,
RA Larson S., Lee-Lin S.-Q., Legaspi R., Madden M., Maduro Q.L., Maduro V.B.,
RA Margulies E.H., Masiello C., Maskeri B., McDowell J., Mojidi H.A.,
RA Mullikin J.C., Oestreicher J.S., Park M., Portnoy M.E., Prasad A., Puri O.,
RA Reddix-Dugue N., Schandler K., Schueler M.G., Sison C., Stantripop S.,
RA Stephen E., Taye A., Thomas J.W., Thomas P.J., Tsipouri V., Ung L.,
RA Vogt J.L., Wetherby K.D., Young A., Green E.D.;
RT "NISC comparative sequencing initiative.";
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
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; DP000183; ABI93652.1; -; Genomic_DNA.
DR RefSeq; XP_004741975.1; XM_004741918.2.
DR AlphaFoldDB; Q07E24; -.
DR SMR; Q07E24; -.
DR STRING; 9668.ENSMPUP00000007141; -.
DR GeneID; 101675655; -.
DR KEGG; mpuf:101675655; -.
DR CTD; 4233; -.
DR eggNOG; KOG0836; Eukaryota.
DR eggNOG; KOG1095; Eukaryota.
DR eggNOG; KOG3610; Eukaryota.
DR InParanoid; Q07E24; -.
DR Proteomes; UP000000715; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:UniProtKB-EC.
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:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 3.
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 3: Inferred from homology;
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..1382
FT /note="Hepatocyte growth factor receptor"
FT /id="PRO_0000260426"
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..1382
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 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"
SQ SEQUENCE 1382 AA; 154655 MW; FA94AFA93BCD9681 CRC64;
MRAPAVLAPG ILVLLFTLVQ RSCGECKEAL VKSEMNVNMK YQLPNFTAET PIQNVVLHKH
HIYLGAVNYI YVLNDKDLQK VAEYKTGPVL EHPDCSPCQD CSHKANLSGA VWKDNINMAL
LIDIYYDDQL ISCGSVQRGT CQRHVLPRSN TADIQSEVHC MYSPQADEEP GQCPDCVVSA
LGTKVLISEK TRFINFFVGN TINSSSHPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP
EFRDSYPIKY VHAFESNHFI YFLTVQRETL DAQTFHTRVI RFCSVDSGLH SYMEMPLECI
LTEKRRKRST REEVFNILQA AYVGKPGAHL AKQIGANLND DILYGVFARS QPDSAEPMNR
SAVCAFPIKY VNEFFNKIVN KNNVRCLQHF YGPNHEHCFN RTLLRNSSGC EVRSDEYRTE
FTTALQRVDL FMGQFNQVLL TSISTFIKGD LTIANLGTSE GRFMQVVVSR SGSSTPHVNF
RLDSHPVSPE AIVEHPLNQN GYTLVVTGKK ITKIPLNGLG CEHFQSCSQC LSAPPFVQCG
WCHDKCVQLE ECPTGTWTQE ICLPTIYEVF PTSAPLEGGT MLTICGWDFG FRRNNKFDLK
KTKVLLGNES CTLTLSESTT NMLKCTVGPA VNEHFNISII IANGRGTAQY SKFSYVDPII
TSISPSYGPK TGGTLLTLNG KYLNSGNSRH ISIGGETCTL KSVSDSILEC YTPAQTTPTE
FPIKLKIDLA NREMNSFSYQ EDPIVYAIHP TKSFISGGST ITAIGKNLHS VSVLRMGINV
HEARRNFTVA CQHRSNSEII CCTTPSLQQL SLQLPLKTKA FFMLDGIHSK YFDLIYVHNP
VFKPFEKPVM ISIGNENVLE IKGNDIDPEA VKGEVLKVGN KSCETIYSDS EAVLCKVPND
LLKLNNELNI EWKQAVSSTI LGKVIVQPDQ NFTGLIVGVI SISLIVLLLL GLFLWLKRRK
QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE SVDYRATFPE DQFPNSSQNG
SCRQVQYPLT DLSPMLTSGD SDISSPLLQN TVHIDLSALN PELVQAVQHV VIGPSSLIVH
FNEVIGRGHF GCVYHGTLLD NDDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV
LSLLGICLRS EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK
FVHRDLAARN CMLDEKFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW MALESLQTQK
FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG RRLLQPEYCP DPLYEVMLKC
WHPKAELRPS FSELVSRISA IFSTFIGEHY VHVNATYVNV KCVAPYPSLL SSQDIIDGEG
DT
