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Q75ZY9

- MET_CANFA

UniProt

Q75ZY9 - MET_CANFA

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Protein

Hepatocyte growth factor receptor

Gene
MET
Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - 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.1 Publication

Catalytic activityi

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

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei308 – 3092Cleavage Reviewed prediction
Binding sitei1111 – 11111ATP By similarity
Active sitei1205 – 12051Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1085 – 10939ATP By similarity

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
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 familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
ProteomesiUP000002254: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 935911Extracellular Reviewed predictionAdd
BLAST
Transmembranei936 – 95621Helical; Reviewed predictionAdd
BLAST
Topological domaini957 – 1379423Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424 Reviewed predictionAdd
BLAST
Chaini25 – 13821358Hepatocyte growth factor receptorPRO_0000024439Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi45 – 451N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi95 ↔ 101 By similarity
Disulfide bondi98 ↔ 160 By similarity
Glycosylationi106 – 1061N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi133 ↔ 141 By similarity
Disulfide bondi173 ↔ 176 By similarity
Glycosylationi203 – 2031N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi299 ↔ 364 By similarity
Glycosylationi359 – 3591N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi386 ↔ 398 By similarity
Glycosylationi400 – 4001N-linked (GlcNAc...) Reviewed prediction
Glycosylationi406 – 4061N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi521 ↔ 539 By similarity
Disulfide bondi527 ↔ 562 By similarity
Disulfide bondi530 ↔ 546 By similarity
Disulfide bondi542 ↔ 552 By similarity
Glycosylationi608 – 6081N-linked (GlcNAc...) Reviewed prediction
Glycosylationi636 – 6361N-linked (GlcNAc...) Reviewed prediction
Glycosylationi786 – 7861N-linked (GlcNAc...) Reviewed prediction
Glycosylationi880 – 8801N-linked (GlcNAc...) Reviewed prediction
Glycosylationi931 – 9311N-linked (GlcNAc...) Reviewed prediction
Modified residuei978 – 9781Phosphothreonine By similarity
Modified residuei991 – 9911Phosphoserine By similarity
Modified residuei998 – 9981Phosphoserine By similarity
Modified residuei1001 – 10011Phosphoserine By similarity
Modified residuei1004 – 10041Phosphotyrosine By similarity
Modified residuei1231 – 12311Phosphotyrosine By similarity
Modified residuei1235 – 12351Phosphotyrosine; by autocatalysis By similarity
Modified residuei1236 – 12361Phosphotyrosine; by autocatalysis By similarity
Modified residuei1290 – 12901Phosphothreonine By similarity
Modified residuei1350 – 13501Phosphotyrosine; by autocatalysis By similarity
Modified residuei1357 – 13571Phosphotyrosine; by autocatalysis By similarity
Modified residuei1366 – 13661Phosphotyrosine By 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.
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation 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.

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000005067.

Structurei

3D structure databases

ProteinModelPortaliQ75ZY9.
SMRiQ75ZY9. Positions 40-742, 1047-1347.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1213 – 1382170Interaction with RANBP9 By similarityAdd
BLAST
Regioni1321 – 136040Interaction with MUC20 By 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

Contains 3 IPT/TIG domains.
Contains 1 Sema domain.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
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.
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.

Q75ZY9-1 [UniParc]FASTAAdd to Basket

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MKAPAVLAPG ILVLLFTLVQ KSYGECKEAL VKSEMNVNMK YQLPNFTAET     50
PIQNVVLHKH HIYLGAVNYI YVLNDKDLQK VAEYKTGPVL EHPDCSPCQD 100
CSHKANLSGG VWEDNINMAL LVDTYYDDQL ISCGSVHRGT CQRHILPPSN 150
IADIQSEVHC MYSSQADEEP SQCPDCVVSA LGTKVLISEK DRFINFFVGN 200
TINSSDHPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP EFRDSYPIKY 250
VHAFESNHFI YFLTVQRETL DAQTFHTRII RFCSVDSGLH SYMEMPLECI 300
LTEKRRKRST REEVFNILQA AYVSKPGAHL AKQIGANLND DILYGVFAQS 350
KPDSAEPMNR SAVCAFPIKY VNEFFNKIVN KNNVRCLQHF YGPNHEHCFN 400
RTLLRNSSGC EARNDEYRTE FTTALQRVDL FMGQFNQVLL TSISTFIKGD 450
LTIANLGTSE GRFMQVVVSR SGLSTPHVNF RLDSHPVSPE AIVEHPLNQN 500
GYTLVVTGKK ITRIPLNGLG CEHFQSCSQC LSAPPFVQCG WCHDRCVHLE 550
ECPTGAWTQE VCLPAIYEVF PTSAPLEGGT VLTVCGWDFG FRRNNKFDLK 600
KTKVFLGNES CTLTLSESTT NMLKCTVGPA VNEHFNISII ISNGRGTAQY 650
STFSYVDPII TSISPSYGPK NGGTLLTLTG KYLNSGNSRH ISMGGKTCTL 700
KSVSDSILEC YTPAQATATE FPIKLKIDLA NREMNSFSYQ EDPIVYAIHP 750
TKSFISGGST ITAVGKNLNS VSVLRMVIDV HETRRNFTVA CQHRSNSEII 800
CCTTPSLQQL NLQLPLKTKA FFMLDGIHSK YFDLIYVHNP VFKPFEKPVM 850
ISIGNENVLE IKGNDIDPEA VKGEVLKVGN KSCETIYSDS KAVLCKVPND 900
LLKLNNELNI EWKQAVSSTV LGKVIVQPDQ NFTGLIAGVI SISTIVLLLL 950
GLFLWLKRKK QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE 1000
SVDYRATFPE DQFPNSSQNG SCRQVQYPLT DLSPMLTSGD SDISSPLLQN 1050
TVHIDLSALN PELVQAVQHV VIGPSSLIVH FNEVIGRGHF GCVYHGTLLD 1100
NDDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV LSLLGICLRS 1150
EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK 1200
FVHRDLAARN CMLDEKFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW 1250
MALESLQTQK FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG 1300
RRLLQPEYCP DPLYEVMLKC WHPRAELRPS FSELVSRISA IFSTFIGEHY 1350
VHVNATYVNV KCVAPYPSLL SSQDNIDGEG DT 1382
Length:1,382
Mass (Da):154,637
Last modified:July 5, 2004 - v1
Checksum:i12BCF8E83821B2F9
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AB118945 mRNA. Translation: BAC84966.1 .
AY543631 mRNA. Translation: AAS48569.1 .
DP000236 Genomic DNA. Translation: AAR16267.1 .
RefSeqi NP_001002963.1. NM_001002963.1.
UniGenei Cfa.144.

3D structure databases

ProteinModelPortali Q75ZY9.
SMRi Q75ZY9. Positions 40-742, 1047-1347.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9615.ENSCAFP00000005067.

Chemistry

ChEMBLi CHEMBL2046265.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 403438.
KEGGi cfa:403438.

Organism-specific databases

CTDi 4233.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000220900.
HOVERGENi HBG006348.
InParanoidi Q75ZY9.
KOi K05099.

Miscellaneous databases

NextBioi 20816956.

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

« Hide 'large scale' publications
  1. "Morecular cloning of the canine c-Met/HGF receptor and it's expression in normal canine tissues."
    Neo S., Furuichi M., Watanabe M., Hisasue M., Tsuchiya R., Hisamatsu S., Kansaku N., Yamada T.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Characterization of the receptor tyrosine kinase Met and its autocrine loop in canine osteosarcoma cell lines."
    Liao A.T., Chien M.B., London C.A.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Comparative analyses of multi-species sequences from targeted genomic regions."
    Thomas J.W., Touchman J.W., Blakesley R.W., Bouffard G.G., Beckstrom-Sternberg S.M., Margulies E.H., Blanchette M., Siepel A.C., Thomas P.J., McDowell J.C., Maskeri B., Hansen N.F., Schwartz M.S., Weber R.J., Kent W.J., Karolchik D., Bruen T.C., Bevan R.
    , Cutler D.J., Schwartz S., Elnitski L., Idol J.R., Prasad A.B., Lee-Lin S.-Q., Maduro V.V.B., Summers T.J., Portnoy M.E., Dietrich N.L., Akhter N., Ayele K., Benjamin B., Cariaga K., Brinkley C.P., Brooks S.Y., Granite S., Guan X., Gupta J., Haghighi P., Ho S.-L., Huang M.C., Karlins E., Laric P.L., Legaspi R., Lim M.J., Maduro Q.L., Masiello C.A., Mastrian S.D., McCloskey J.C., Pearson R., Stantripop S., Tiongson E.E., Tran J.T., Tsurgeon C., Vogt J.L., Walker M.A., Wetherby K.D., Wiggins L.S., Young A.C., Zhang L.-H., Osoegawa K., Zhu B., Zhao B., Shu C.L., De Jong P.J., Lawrence C.E., Smit A.F., Chakravarti A., Haussler D., Green P., Miller W., Green E.D.
    Nature 424:788-793(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Involvement of hepatocyte growth factor in kidney development."
    Santos O.F., Barros E.J., Yang X.M., Matsumoto K., Nakamura T., Park M., Nigam S.K.
    Dev. Biol. 163:525-529(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN KIDNEY DEVELOPMENT.

Entry informationi

Entry nameiMET_CANFA
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: June 11, 2014
This is version 91 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

Similar proteinsi