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Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: 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).By similarity1 Publication

Catalytic activityi

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

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1111ATPPROSITE-ProRule annotation1
Active sitei1205Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1085 – 1093ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 935ExtracellularSequence analysisAdd BLAST911
Transmembranei936 – 956HelicalSequence analysisAdd BLAST21
Topological domaini957 – 1379CytoplasmicSequence analysisAdd BLAST423

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Chemistry databases

ChEMBLiCHEMBL2046265.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000002443925 – 1382Hepatocyte growth factor receptorAdd BLAST1358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi45N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi95 ↔ 101PROSITE-ProRule annotation
Disulfide bondi98 ↔ 160PROSITE-ProRule annotation
Glycosylationi106N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi133 ↔ 141PROSITE-ProRule annotation
Disulfide bondi173 ↔ 176PROSITE-ProRule annotation
Glycosylationi203N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi299 ↔ 364PROSITE-ProRule annotation
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi386 ↔ 398PROSITE-ProRule annotation
Glycosylationi400N-linked (GlcNAc...)Sequence analysis1
Glycosylationi406N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi521 ↔ 539PROSITE-ProRule annotation
Disulfide bondi527 ↔ 562PROSITE-ProRule annotation
Disulfide bondi530 ↔ 546PROSITE-ProRule annotation
Disulfide bondi542 ↔ 552PROSITE-ProRule annotation
Glycosylationi608N-linked (GlcNAc...)Sequence analysis1
Glycosylationi636N-linked (GlcNAc...)Sequence analysis1
Glycosylationi786N-linked (GlcNAc...)Sequence analysis1
Glycosylationi880N-linked (GlcNAc...)Sequence analysis1
Glycosylationi931N-linked (GlcNAc...)Sequence analysis1
Modified residuei967PhosphoserineBy similarity1
Modified residuei978PhosphothreonineBy similarity1
Modified residuei991PhosphoserineBy similarity1
Modified residuei998PhosphoserineBy similarity1
Modified residuei1001PhosphoserineBy similarity1
Modified residuei1004PhosphotyrosineBy similarity1
Modified residuei1231PhosphotyrosineBy similarity1
Modified residuei1235Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1236Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1290PhosphothreonineBy similarity1
Modified residuei1350Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1357Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1366PhosphotyrosineBy similarity1

Post-translational modificationi

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).By similarity
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei308 – 309CleavageSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ75ZY9.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000041478.

Chemistry databases

BindingDBiQ75ZY9.

Structurei

3D structure databases

ProteinModelPortaliQ75ZY9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 516SemaPROSITE-ProRule annotationAdd BLAST490
Domaini564 – 656IPT/TIG 1Add BLAST93
Domaini658 – 740IPT/TIG 2Add BLAST83
Domaini743 – 837IPT/TIG 3Add BLAST95
Domaini1079 – 1346Protein kinasePROSITE-ProRule annotationAdd BLAST268

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1213 – 1382Interaction with RANBP9By similarityAdd BLAST170
Regioni1321 – 1360Interaction with MUC20By similarityAdd BLAST40

Domaini

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

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
Contains 3 IPT/TIG domains.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 Sema domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiQ75ZY9.
KOiK05099.

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.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
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.
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.

Q75ZY9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKAPAVLAPG ILVLLFTLVQ KSYGECKEAL VKSEMNVNMK YQLPNFTAET
60 70 80 90 100
PIQNVVLHKH HIYLGAVNYI YVLNDKDLQK VAEYKTGPVL EHPDCSPCQD
110 120 130 140 150
CSHKANLSGG VWEDNINMAL LVDTYYDDQL ISCGSVHRGT CQRHILPPSN
160 170 180 190 200
IADIQSEVHC MYSSQADEEP SQCPDCVVSA LGTKVLISEK DRFINFFVGN
210 220 230 240 250
TINSSDHPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP EFRDSYPIKY
260 270 280 290 300
VHAFESNHFI YFLTVQRETL DAQTFHTRII RFCSVDSGLH SYMEMPLECI
310 320 330 340 350
LTEKRRKRST REEVFNILQA AYVSKPGAHL AKQIGANLND DILYGVFAQS
360 370 380 390 400
KPDSAEPMNR SAVCAFPIKY VNEFFNKIVN KNNVRCLQHF YGPNHEHCFN
410 420 430 440 450
RTLLRNSSGC EARNDEYRTE FTTALQRVDL FMGQFNQVLL TSISTFIKGD
460 470 480 490 500
LTIANLGTSE GRFMQVVVSR SGLSTPHVNF RLDSHPVSPE AIVEHPLNQN
510 520 530 540 550
GYTLVVTGKK ITRIPLNGLG CEHFQSCSQC LSAPPFVQCG WCHDRCVHLE
560 570 580 590 600
ECPTGAWTQE VCLPAIYEVF PTSAPLEGGT VLTVCGWDFG FRRNNKFDLK
610 620 630 640 650
KTKVFLGNES CTLTLSESTT NMLKCTVGPA VNEHFNISII ISNGRGTAQY
660 670 680 690 700
STFSYVDPII TSISPSYGPK NGGTLLTLTG KYLNSGNSRH ISMGGKTCTL
710 720 730 740 750
KSVSDSILEC YTPAQATATE FPIKLKIDLA NREMNSFSYQ EDPIVYAIHP
760 770 780 790 800
TKSFISGGST ITAVGKNLNS VSVLRMVIDV HETRRNFTVA CQHRSNSEII
810 820 830 840 850
CCTTPSLQQL NLQLPLKTKA FFMLDGIHSK YFDLIYVHNP VFKPFEKPVM
860 870 880 890 900
ISIGNENVLE IKGNDIDPEA VKGEVLKVGN KSCETIYSDS KAVLCKVPND
910 920 930 940 950
LLKLNNELNI EWKQAVSSTV LGKVIVQPDQ NFTGLIAGVI SISTIVLLLL
960 970 980 990 1000
GLFLWLKRKK QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE
1010 1020 1030 1040 1050
SVDYRATFPE DQFPNSSQNG SCRQVQYPLT DLSPMLTSGD SDISSPLLQN
1060 1070 1080 1090 1100
TVHIDLSALN PELVQAVQHV VIGPSSLIVH FNEVIGRGHF GCVYHGTLLD
1110 1120 1130 1140 1150
NDDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV LSLLGICLRS
1160 1170 1180 1190 1200
EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK
1210 1220 1230 1240 1250
FVHRDLAARN CMLDEKFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW
1260 1270 1280 1290 1300
MALESLQTQK FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG
1310 1320 1330 1340 1350
RRLLQPEYCP DPLYEVMLKC WHPRAELRPS FSELVSRISA IFSTFIGEHY
1360 1370 1380
VHVNATYVNV KCVAPYPSLL SSQDNIDGEG DT
Length:1,382
Mass (Da):154,637
Last modified:July 5, 2004 - v1
Checksum:i12BCF8E83821B2F9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB118945 mRNA. Translation: BAC84966.1.
AY543631 mRNA. Translation: AAS48569.1.
DP000236 Genomic DNA. Translation: AAR16267.1.
RefSeqiNP_001002963.1. NM_001002963.1.
UniGeneiCfa.144.

Genome annotation databases

GeneIDi403438.
KEGGicfa:403438.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB118945 mRNA. Translation: BAC84966.1.
AY543631 mRNA. Translation: AAS48569.1.
DP000236 Genomic DNA. Translation: AAR16267.1.
RefSeqiNP_001002963.1. NM_001002963.1.
UniGeneiCfa.144.

3D structure databases

ProteinModelPortaliQ75ZY9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000041478.

Chemistry databases

BindingDBiQ75ZY9.
ChEMBLiCHEMBL2046265.

Proteomic databases

PaxDbiQ75ZY9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi403438.
KEGGicfa:403438.

Organism-specific databases

CTDi4233.

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiQ75ZY9.
KOiK05099.

Miscellaneous databases

PROiQ75ZY9.

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.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
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.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiMET_CANLF
AccessioniPrimary (citable) accession number: Q75ZY9
Secondary accession number(s): A0M8U9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 105 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.