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Q2QLA9

- MET_HORSE

UniProt

Q2QLA9 - MET_HORSE

Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Equus caballus (Horse)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 1 (24 Jan 2006)
      Previous versions | rss
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    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 similarity

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sitei307 – 3082CleavageSequence Analysis
    Binding sitei1110 – 11101ATPPROSITE-ProRule annotation
    Active sitei1204 – 12041Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1084 – 10929ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. hepatocyte growth factor-activated receptor activity Source: Ensembl

    GO - Biological processi

    1. activation of MAPK activity Source: Ensembl
    2. adult behavior Source: Ensembl
    3. brain development Source: Ensembl
    4. branching morphogenesis of an epithelial tube Source: Ensembl
    5. glucose homeostasis Source: Ensembl
    6. liver development Source: Ensembl
    7. muscle cell migration Source: Ensembl
    8. myoblast proliferation Source: Ensembl
    9. myotube differentiation Source: Ensembl
    10. negative regulation of hydrogen peroxide-mediated programmed cell death Source: Ensembl
    11. placenta development Source: Ensembl
    12. positive chemotaxis Source: UniProtKB
    13. positive regulation of endothelial cell chemotaxis Source: UniProtKB
    14. positive regulation of glucose transport Source: Ensembl
    15. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    16. protein autophosphorylation Source: Ensembl
    17. regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Source: Ensembl
    18. semaphorin-plexin signaling pathway Source: UniProtKB
    19. skeletal muscle tissue development Source: Ensembl

    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
    OrganismiEquus caballus (Horse)
    Taxonomic identifieri9796 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
    ProteomesiUP000002281: Chromosome 4

    Subcellular locationi

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

    GO - Cellular componenti

    1. basal plasma membrane Source: Ensembl
    2. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Chaini25 – 13811357Hepatocyte growth factor receptorPRO_0000226362Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi45 – 451N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi95 ↔ 101PROSITE-ProRule annotation
    Disulfide bondi98 ↔ 160PROSITE-ProRule annotation
    Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi133 ↔ 141PROSITE-ProRule annotation
    Disulfide bondi172 ↔ 175PROSITE-ProRule annotation
    Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi298 ↔ 363PROSITE-ProRule annotation
    Glycosylationi358 – 3581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi385 ↔ 397PROSITE-ProRule annotation
    Glycosylationi399 – 3991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi405 – 4051N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi449 – 4491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi520 ↔ 538PROSITE-ProRule annotation
    Disulfide bondi526 ↔ 561PROSITE-ProRule annotation
    Disulfide bondi529 ↔ 545PROSITE-ProRule annotation
    Disulfide bondi541 ↔ 551PROSITE-ProRule annotation
    Glycosylationi553 – 5531N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi607 – 6071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi635 – 6351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi785 – 7851N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi879 – 8791N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi930 – 9301N-linked (GlcNAc...)Sequence Analysis
    Modified residuei977 – 9771PhosphothreonineBy similarity
    Modified residuei990 – 9901PhosphoserineBy similarity
    Modified residuei997 – 9971PhosphoserineBy similarity
    Modified residuei1000 – 10001PhosphoserineBy similarity
    Modified residuei1003 – 10031PhosphotyrosineBy similarity
    Modified residuei1230 – 12301PhosphotyrosineBy similarity
    Modified residuei1234 – 12341Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1235 – 12351Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1289 – 12891PhosphothreonineBy similarity
    Modified residuei1349 – 13491Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1356 – 13561Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1365 – 13651PhosphotyrosineBy similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ2QLA9.

    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-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.By similarity

    Protein-protein interaction databases

    STRINGi9796.ENSECAP00000008993.

    Structurei

    3D structure databases

    ProteinModelPortaliQ2QLA9.
    SMRiQ2QLA9. Positions 40-741, 1046-1346.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini25 – 934910ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini956 – 1381426CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei935 – 95521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 515489SemaPROSITE-ProRule annotationAdd
    BLAST
    Domaini563 – 65593IPT/TIG 1Add
    BLAST
    Domaini657 – 73983IPT/TIG 2Add
    BLAST
    Domaini742 – 83695IPT/TIG 3Add
    BLAST
    Domaini1078 – 1345268Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1212 – 1381170Interaction with RANBP9By similarityAdd
    BLAST
    Regioni1320 – 135940Interaction with MUC20By similarityAdd
    BLAST

    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

    eggNOGiCOG0515.
    GeneTreeiENSGT00720000108377.
    HOGENOMiHOG000220900.
    HOVERGENiHBG006348.
    InParanoidiQ2QLA9.
    KOiK05099.
    OMAiQRVDLFM.
    OrthoDBiEOG7J70DR.
    TreeFamiTF317402.

    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.
    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]
    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.
    SSF103575. SSF103575. 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.

    Q2QLA9-1 [UniParc]FASTAAdd to Basket

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    MKAPAVLAPG ILVLLFTLVQ KSDGECKEAL VKSEMNVNMK YQLPNFTAET     50
    PIQNVVLHKH HIYLGATNYI YVLNDKDLQK VAEYKTGPVL EHPDCFPCQD 100
    CSRKANLSGG AWKDNINMAL LVDTYYDDQL ISCGSVHRGT CQRHVLPLNN 150
    VADIQSEVYC MYSPQAEEPH QCPDCVVSAL GTKVLLSEKD RFVTFFVGNT 200
    INSSYLPDHS LHSISVRRLK ETQDGFKFLT DQSYIDVLPE FRDSYPIKYI 250
    HAFESNHFIY FLTVQRETLD AQTFHTRIIR FCSVDSGLHS YMEMPLECIL 300
    TEKRRKRSTS EEVFNILQAA YVSKPGAHLA KQIGANLNDD ILYGVFAQSK 350
    PDSAEPMNRS AVCAFPVKYV NEFFNKIVNK NNVRCLQHFY GPHHEHCFNR 400
    TLLRNSSGCE VRNDEYRTEF TTALQRVDLF MGQFNQVLLT SISTFIKGNL 450
    TIANLGTSEG RFMQVVVSRS GSSTPHVNFH LDSHPVSPEV IVEHPLNQNG 500
    YTLVVTGKKI TKIPLNGLGC EHFQSCSQCL SAPPFVQCGW CHDKCVRLEE 550
    CHNGTWTQEI CLPTIYKVFP TSAPLEGGTT LTVCGWDFGF RKNNKLDSKK 600
    TKVLLGNESC TLTLSESTSN TLKCTVGPAM NERFNISITV SNSRGTARYS 650
    TFSYVDPIIT SISPSYGPKT GGTLLTLTGK YLNSGNSRHI SIGGKTCTLK 700
    SVSDSILECY TPAQTTPTEF PVKLKIDLAN REMNSFSYRE DPIVYEIHPT 750
    KSFISGGSTI TGVGKNLNSV SVLRMVINVR EAGRNFTVAC QHRSNSEIIC 800
    CTTPSLQQLN LQLPLKTKAF FMLDGIHSKY FDLIYVHNPV FKPFEKPVMI 850
    SIGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHSHSE AVLCTVPSDL 900
    LKLNSELNIE WKQAVSSTIL GKVIVQPDQN FTGLIVGVVS ISIILLLLLG 950
    LFLWLKRRKQ IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES 1000
    VDYRATFPED QFPNSSQNGS CRQVQYPLTD LSPILTSGDS DISSPLLQNT 1050
    VHIDLSALNP ELVQAVQHVV IGPSSLIVHF NEVIGRGHFG CVYHGTLLDN 1100
    DDKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL SLLGICLRSE 1150
    GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 1200
    VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM 1250
    ALESLQTQKF TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR 1300
    RLLQPEYCPD PLYEVMLKCW HPKAELRPSF SELVSRISAI FSTFIGEHYV 1350
    HVNATYVNVK CVAPYPSLLS SQDNVDGEVD T 1381
    Length:1,381
    Mass (Da):154,561
    Last modified:January 24, 2006 - v1
    Checksum:i19D761B3344A5798
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DP000020 Genomic DNA. Translation: ABB89800.1.
    RefSeqiNP_001107619.1. NM_001114147.1.
    UniGeneiEca.16194.

    Genome annotation databases

    EnsembliENSECAT00000011493; ENSECAP00000008993; ENSECAG00000010385.
    GeneIDi100056013.
    KEGGiecb:100056013.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DP000020 Genomic DNA. Translation: ABB89800.1 .
    RefSeqi NP_001107619.1. NM_001114147.1.
    UniGenei Eca.16194.

    3D structure databases

    ProteinModelPortali Q2QLA9.
    SMRi Q2QLA9. Positions 40-741, 1046-1346.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9796.ENSECAP00000008993.

    Proteomic databases

    PRIDEi Q2QLA9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSECAT00000011493 ; ENSECAP00000008993 ; ENSECAG00000010385 .
    GeneIDi 100056013.
    KEGGi ecb:100056013.

    Organism-specific databases

    CTDi 4233.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00720000108377.
    HOGENOMi HOG000220900.
    HOVERGENi HBG006348.
    InParanoidi Q2QLA9.
    KOi K05099.
    OMAi QRVDLFM.
    OrthoDBi EOG7J70DR.
    TreeFami TF317402.

    Family and domain databases

    Gene3Di 2.130.10.10. 1 hit.
    2.60.40.10. 3 hits.
    InterProi IPR013783. 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 ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF01437. PSI. 1 hit.
    PF01403. Sema. 1 hit.
    PF01833. TIG. 3 hits.
    [Graphical view ]
    PIRSFi PIRSF000617. TyrPK_HGF-R. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00429. IPT. 4 hits.
    SM00423. PSI. 1 hit.
    SM00630. Sema. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF101912. SSF101912. 1 hit.
    SSF103575. SSF103575. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF81296. SSF81296. 3 hits.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS51004. SEMA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

    Entry informationi

    Entry nameiMET_HORSE
    AccessioniPrimary (citable) accession number: Q2QLA9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 7, 2006
    Last sequence update: January 24, 2006
    Last modified: October 1, 2014
    This is version 82 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

    External Data

    Dasty 3