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Q108U6

- MET_LOXAF

UniProt

Q108U6 - MET_LOXAF

Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Loxodonta africana (African elephant)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 68 (01 Oct 2014)
      Sequence version 1 (22 Aug 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
    Sitei308 – 3092CleavageSequence Analysis
    Binding sitei1111 – 11111ATPPROSITE-ProRule annotation
    Active sitei1205 – 12051Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1085 – 10939ATPPROSITE-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
    OrganismiLoxodonta africana (African elephant)
    Taxonomic identifieri9785 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaAfrotheriaProboscideaElephantidaeLoxodonta
    ProteomesiUP000007646: Unplaced

    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 – 13821358Hepatocyte growth factor receptorPRO_0000250465Add
    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 bondi173 ↔ 176PROSITE-ProRule annotation
    Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi299 ↔ 364PROSITE-ProRule annotation
    Glycosylationi359 – 3591N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi386 ↔ 398PROSITE-ProRule annotation
    Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi406 – 4061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi450 – 4501N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi521 ↔ 539PROSITE-ProRule annotation
    Disulfide bondi527 ↔ 562PROSITE-ProRule annotation
    Disulfide bondi530 ↔ 546PROSITE-ProRule annotation
    Disulfide bondi542 ↔ 552PROSITE-ProRule annotation
    Glycosylationi608 – 6081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi636 – 6361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi751 – 7511N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi786 – 7861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi880 – 8801N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi931 – 9311N-linked (GlcNAc...)Sequence Analysis
    Modified residuei978 – 9781PhosphothreonineBy similarity
    Modified residuei991 – 9911PhosphoserineBy similarity
    Modified residuei998 – 9981PhosphoserineBy similarity
    Modified residuei1001 – 10011PhosphoserineBy similarity
    Modified residuei1004 – 10041PhosphotyrosineBy similarity
    Modified residuei1231 – 12311PhosphotyrosineBy similarity
    Modified residuei1235 – 12351Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1236 – 12361Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1290 – 12901PhosphothreonineBy similarity
    Modified residuei1350 – 13501Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1357 – 13571Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1366 – 13661PhosphotyrosineBy similarity

    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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    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

    Structurei

    3D structure databases

    ProteinModelPortaliQ108U6.
    SMRiQ108U6. Positions 40-742, 1047-1347.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini25 – 935911ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini957 – 1382426CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei936 – 95621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 516490SemaPROSITE-ProRule annotationAdd
    BLAST
    Domaini564 – 65693IPT/TIG 1Add
    BLAST
    Domaini658 – 74083IPT/TIG 2Add
    BLAST
    Domaini743 – 83795IPT/TIG 3Add
    BLAST
    Domaini1079 – 1346268Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1213 – 1382170Interaction with RANBP9By similarityAdd
    BLAST
    Regioni1321 – 136040Interaction 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

    HOGENOMiHOG000220900.
    HOVERGENiHBG006348.

    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.

    Q108U6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKAPAVLAPG VLVLLFTLVR KSHGECEEAL AKSKMNVNMK YQLPNFTADT     50
    PIQNVVLHEH HIFLGAINNI YVLNDKDLQK VAEYKTGPVL EHPDCLPCQD 100
    CSSKANLSGS VWKDNINMAL LVDTYYDDQL ITCGSVNRGT CQRHVLPPDN 150
    PADIHSKVHC MYSPQADEEP SKCPDCVVSA LGTKVLLTEK DRFINFFVGN 200
    TVNSSYLPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP EFRDSYPIKY 250
    VHAFKHNQFI YFLTVQRETL ESQTFHTRII RFCSVDSGLH SYMEMPLECI 300
    LTEKRRKRSA REEVFNILQA AYVSKPGAYL AKQIGALPDD DILYGVFAQS 350
    KLDSAEPMNR SAVCAFPIKY VNDFFNKIVN KNNVRCLQHF YGPNHEHCFN 400
    RTLLRNSSGC EVRRDEYRTE FTTALQRVDL FTGQFNQVLL TSISTFIKGN 450
    LTIANLGTSE GRFMQVVVSR SGLTTPHVNF RLDSHAVSPE VILEHPLNQN 500
    GYTLVITGKK ITKIPLDGLG CDHFQSCSQC LSAPSFVQCG WCHNKCARAE 550
    ECPNGMWTQE ICLPTIYEVF PTSAPLEGGT TLTVCGWDFG FRRNNKFDLK 600
    KTRVLIGNDS CTLTLSESTT NTLKCTVGPA MNKHFNLSII ISNGRGTARY 650
    RTFSYVEPVI TSISPSYGPK AGGTLVTLTG KYLNSGNSRH ISIGGKTCTL 700
    KSVSDSVLEC YTPAQSISTD FPVKLKIDLA NREAYSFSYQ EDPTVYEIHP 750
    NKSFISGGST ITGIGKNLNS VSVPRMVINV QEAGRNFTVA CQHRSNSEII 800
    CCTTPSLQQL NLQLPLKTKA FFMLDGIHSN YFDLIYVHNP VFKPFKKPVM 850
    ISMGNENVLE IKGDYIDPEA VKGEVLKVGN KSCENIHLQS EAVLCTVPND 900
    LLKLNSELNI EWKQAVSSTV LGKVIVQPDQ NFTGLIVGVV SISIILLLLL 950
    GLFLWLKKRK QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE 1000
    SVDYRATFPE DQFPNSSQNG SCRQVQYPLT DMSPILTNGD SDSSIPLLQN 1050
    NVHIDLSALN PELVQAVQHV VIGPSSLIVH FNEVIGRGHF GCVYHGTLLD 1100
    NGDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV LSLLGICLRS 1150
    EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK 1200
    FVHRDLAARN CMLDEKFTVK VADFGLARDV YDKEYYSVHN KTGAKLPVKW 1250
    MALESLQTQK FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG 1300
    RRLLQPEYCP DPLYEVMLKC WHPKAEMRPS FSELVSRISA IFSTFIGEHY 1350
    VHVNTTYVNV KCVAPYPSLL SSQDSVDDEV DT 1382
    Length:1,382
    Mass (Da):154,684
    Last modified:August 22, 2006 - v1
    Checksum:iB22F334F1CC126BC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DP000087 Genomic DNA. Translation: ABG66646.1.
    RefSeqiXP_003407277.1. XM_003407229.1.

    Genome annotation databases

    GeneIDi100656285.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DP000087 Genomic DNA. Translation: ABG66646.1 .
    RefSeqi XP_003407277.1. XM_003407229.1.

    3D structure databases

    ProteinModelPortali Q108U6.
    SMRi Q108U6. Positions 40-742, 1047-1347.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100656285.

    Phylogenomic databases

    HOGENOMi HOG000220900.
    HOVERGENi HBG006348.

    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_LOXAF
    AccessioniPrimary (citable) accession number: Q108U6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2006
    Last sequence update: August 22, 2006
    Last modified: October 1, 2014
    This is version 68 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