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Q2QLA9 (MET_HORSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte growth factor receptor

Short name=HGF receptor
EC=2.7.10.1
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name=SF receptor
Tyrosine-protein kinase Met
Gene names
Name:MET
OrganismEquus caballus (Horse) [Reference proteome]
Taxonomic identifier9796 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus

Protein attributes

Sequence length1381 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceInferred from homology

General annotation (Comments)

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.

Catalytic activity

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

Enzyme 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.

Subunit structure

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-1356, 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.

Subcellular location

Membrane; Single-pass type I membrane protein By similarity.

Domain

The kinase domain is involved in SPSB1 binding By similarity.

The beta-propeller Sema domain mediates binding to HGF By similarity.

Post-translational modification

Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2 By similarity.

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

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 3 IPT/TIG domains.

Contains 1 protein kinase domain.

Contains 1 Sema domain.

Ontologies

Keywords
   Cellular componentMembrane
   DiseaseProto-oncogene
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

adult behavior

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

branching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

muscle cell migration

Inferred from electronic annotation. Source: Ensembl

myoblast proliferation

Inferred from electronic annotation. Source: Ensembl

myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of hydrogen peroxide-mediated programmed cell death

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasal plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

hepatocyte growth factor-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 13811357Hepatocyte growth factor receptor
PRO_0000226362

Regions

Topological domain25 – 934910Extracellular Potential
Transmembrane935 – 95521Helical; Potential
Topological domain956 – 1381426Cytoplasmic Potential
Domain27 – 515489Sema
Domain563 – 65593IPT/TIG 1
Domain657 – 73983IPT/TIG 2
Domain742 – 83695IPT/TIG 3
Domain1078 – 1345268Protein kinase
Nucleotide binding1084 – 10929ATP By similarity
Region1212 – 1381170Interaction with RANBP9 By similarity
Region1320 – 135940Interaction with MUC20 By similarity

Sites

Active site12041Proton acceptor By similarity
Binding site11101ATP By similarity
Site307 – 3082Cleavage Potential

Amino acid modifications

Modified residue9771Phosphothreonine By similarity
Modified residue9901Phosphoserine By similarity
Modified residue9971Phosphoserine By similarity
Modified residue10001Phosphoserine By similarity
Modified residue10031Phosphotyrosine By similarity
Modified residue12301Phosphotyrosine By similarity
Modified residue12341Phosphotyrosine; by autocatalysis By similarity
Modified residue12351Phosphotyrosine; by autocatalysis By similarity
Modified residue12891Phosphothreonine By similarity
Modified residue13491Phosphotyrosine; by autocatalysis By similarity
Modified residue13561Phosphotyrosine; by autocatalysis By similarity
Modified residue13651Phosphotyrosine By similarity
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation2021N-linked (GlcNAc...) Potential
Glycosylation3581N-linked (GlcNAc...) Potential
Glycosylation3991N-linked (GlcNAc...) Potential
Glycosylation4051N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Glycosylation5531N-linked (GlcNAc...) Potential
Glycosylation6071N-linked (GlcNAc...) Potential
Glycosylation6351N-linked (GlcNAc...) Potential
Glycosylation7851N-linked (GlcNAc...) Potential
Glycosylation8791N-linked (GlcNAc...) Potential
Glycosylation9301N-linked (GlcNAc...) Potential
Disulfide bond95 ↔ 101 By similarity
Disulfide bond98 ↔ 160 By similarity
Disulfide bond133 ↔ 141 By similarity
Disulfide bond172 ↔ 175 By similarity
Disulfide bond298 ↔ 363 By similarity
Disulfide bond385 ↔ 397 By similarity
Disulfide bond520 ↔ 538 By similarity
Disulfide bond526 ↔ 561 By similarity
Disulfide bond529 ↔ 545 By similarity
Disulfide bond541 ↔ 551 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q2QLA9 [UniParc].

Last modified January 24, 2006. Version 1.
Checksum: 19D761B3344A5798

FASTA1,381154,561
        10         20         30         40         50         60 
MKAPAVLAPG ILVLLFTLVQ KSDGECKEAL VKSEMNVNMK YQLPNFTAET PIQNVVLHKH 

        70         80         90        100        110        120 
HIYLGATNYI YVLNDKDLQK VAEYKTGPVL EHPDCFPCQD CSRKANLSGG AWKDNINMAL 

       130        140        150        160        170        180 
LVDTYYDDQL ISCGSVHRGT CQRHVLPLNN VADIQSEVYC MYSPQAEEPH QCPDCVVSAL 

       190        200        210        220        230        240 
GTKVLLSEKD RFVTFFVGNT INSSYLPDHS LHSISVRRLK ETQDGFKFLT DQSYIDVLPE 

       250        260        270        280        290        300 
FRDSYPIKYI HAFESNHFIY FLTVQRETLD AQTFHTRIIR FCSVDSGLHS YMEMPLECIL 

       310        320        330        340        350        360 
TEKRRKRSTS EEVFNILQAA YVSKPGAHLA KQIGANLNDD ILYGVFAQSK PDSAEPMNRS 

       370        380        390        400        410        420 
AVCAFPVKYV NEFFNKIVNK NNVRCLQHFY GPHHEHCFNR TLLRNSSGCE VRNDEYRTEF 

       430        440        450        460        470        480 
TTALQRVDLF MGQFNQVLLT SISTFIKGNL TIANLGTSEG RFMQVVVSRS GSSTPHVNFH 

       490        500        510        520        530        540 
LDSHPVSPEV IVEHPLNQNG YTLVVTGKKI TKIPLNGLGC EHFQSCSQCL SAPPFVQCGW 

       550        560        570        580        590        600 
CHDKCVRLEE CHNGTWTQEI CLPTIYKVFP TSAPLEGGTT LTVCGWDFGF RKNNKLDSKK 

       610        620        630        640        650        660 
TKVLLGNESC TLTLSESTSN TLKCTVGPAM NERFNISITV SNSRGTARYS TFSYVDPIIT 

       670        680        690        700        710        720 
SISPSYGPKT GGTLLTLTGK YLNSGNSRHI SIGGKTCTLK SVSDSILECY TPAQTTPTEF 

       730        740        750        760        770        780 
PVKLKIDLAN REMNSFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV SVLRMVINVR 

       790        800        810        820        830        840 
EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGIHSKY FDLIYVHNPV 

       850        860        870        880        890        900 
FKPFEKPVMI SIGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHSHSE AVLCTVPSDL 

       910        920        930        940        950        960 
LKLNSELNIE WKQAVSSTIL GKVIVQPDQN FTGLIVGVVS ISIILLLLLG LFLWLKRRKQ 

       970        980        990       1000       1010       1020 
IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS 

      1030       1040       1050       1060       1070       1080 
CRQVQYPLTD LSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF 

      1090       1100       1110       1120       1130       1140 
NEVIGRGHFG CVYHGTLLDN DDKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL 

      1150       1160       1170       1180       1190       1200 
SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 

      1210       1220       1230       1240       1250       1260 
VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF 

      1270       1280       1290       1300       1310       1320 
TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 

      1330       1340       1350       1360       1370       1380 
HPKAELRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SQDNVDGEVD 


T 

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DP000020 Genomic DNA. Translation: ABB89800.1.
RefSeqNP_001107619.1. NM_001114147.1.
UniGeneEca.16194.

3D structure databases

ProteinModelPortalQ2QLA9.
SMRQ2QLA9. Positions 40-741, 1046-1346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9796.ENSECAP00000008993.

Proteomic databases

PRIDEQ2QLA9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSECAT00000011493; ENSECAP00000008993; ENSECAG00000010385.
GeneID100056013.
KEGGecb:100056013.

Organism-specific databases

CTD4233.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108377.
HOGENOMHOG000220900.
HOVERGENHBG006348.
InParanoidQ2QLA9.
KOK05099.
OMAQRVDLFM.
OrthoDBEOG7J70DR.
TreeFamTF317402.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProIPR013783. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameMET_HORSE
AccessionPrimary (citable) accession number: Q2QLA9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: January 24, 2006
Last modified: April 16, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families