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Q2QLA9

- MET_HORSE

UniProt

Q2QLA9 - MET_HORSE

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Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Equus caballus (Horse)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi

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

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 934910ExtracellularSequence AnalysisAdd
BLAST
Transmembranei935 – 95521HelicalSequence AnalysisAdd
BLAST
Topological domaini956 – 1381426CytoplasmicSequence AnalysisAdd
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 – 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...

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.
GeneTreeiENSGT00770000120499.
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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        10         20         30         40         50
MKAPAVLAPG ILVLLFTLVQ KSDGECKEAL VKSEMNVNMK YQLPNFTAET
60 70 80 90 100
PIQNVVLHKH HIYLGATNYI YVLNDKDLQK VAEYKTGPVL EHPDCFPCQD
110 120 130 140 150
CSRKANLSGG AWKDNINMAL LVDTYYDDQL ISCGSVHRGT CQRHVLPLNN
160 170 180 190 200
VADIQSEVYC MYSPQAEEPH QCPDCVVSAL GTKVLLSEKD RFVTFFVGNT
210 220 230 240 250
INSSYLPDHS LHSISVRRLK ETQDGFKFLT DQSYIDVLPE FRDSYPIKYI
260 270 280 290 300
HAFESNHFIY FLTVQRETLD AQTFHTRIIR FCSVDSGLHS YMEMPLECIL
310 320 330 340 350
TEKRRKRSTS EEVFNILQAA YVSKPGAHLA KQIGANLNDD ILYGVFAQSK
360 370 380 390 400
PDSAEPMNRS AVCAFPVKYV NEFFNKIVNK NNVRCLQHFY GPHHEHCFNR
410 420 430 440 450
TLLRNSSGCE VRNDEYRTEF TTALQRVDLF MGQFNQVLLT SISTFIKGNL
460 470 480 490 500
TIANLGTSEG RFMQVVVSRS GSSTPHVNFH LDSHPVSPEV IVEHPLNQNG
510 520 530 540 550
YTLVVTGKKI TKIPLNGLGC EHFQSCSQCL SAPPFVQCGW CHDKCVRLEE
560 570 580 590 600
CHNGTWTQEI CLPTIYKVFP TSAPLEGGTT LTVCGWDFGF RKNNKLDSKK
610 620 630 640 650
TKVLLGNESC TLTLSESTSN TLKCTVGPAM NERFNISITV SNSRGTARYS
660 670 680 690 700
TFSYVDPIIT SISPSYGPKT GGTLLTLTGK YLNSGNSRHI SIGGKTCTLK
710 720 730 740 750
SVSDSILECY TPAQTTPTEF PVKLKIDLAN REMNSFSYRE DPIVYEIHPT
760 770 780 790 800
KSFISGGSTI TGVGKNLNSV SVLRMVINVR EAGRNFTVAC QHRSNSEIIC
810 820 830 840 850
CTTPSLQQLN LQLPLKTKAF FMLDGIHSKY FDLIYVHNPV FKPFEKPVMI
860 870 880 890 900
SIGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHSHSE AVLCTVPSDL
910 920 930 940 950
LKLNSELNIE WKQAVSSTIL GKVIVQPDQN FTGLIVGVVS ISIILLLLLG
960 970 980 990 1000
LFLWLKRRKQ IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES
1010 1020 1030 1040 1050
VDYRATFPED QFPNSSQNGS CRQVQYPLTD LSPILTSGDS DISSPLLQNT
1060 1070 1080 1090 1100
VHIDLSALNP ELVQAVQHVV IGPSSLIVHF NEVIGRGHFG CVYHGTLLDN
1110 1120 1130 1140 1150
DDKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL SLLGICLRSE
1160 1170 1180 1190 1200
GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF
1210 1220 1230 1240 1250
VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM
1260 1270 1280 1290 1300
ALESLQTQKF TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR
1310 1320 1330 1340 1350
RLLQPEYCPD PLYEVMLKCW HPKAELRPSF SELVSRISAI FSTFIGEHYV
1360 1370 1380
HVNATYVNVK CVAPYPSLLS SQDNVDGEVD T
Length:1,381
Mass (Da):154,561
Last modified:January 24, 2006 - v1
Checksum:i19D761B3344A5798
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 ENSGT00770000120499.
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: November 26, 2014
This is version 84 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