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Q2IBD8

- MET_PONAB

UniProt

Q2IBD8 - MET_PONAB

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Protein
Hepatocyte growth factor receptor
Gene
MET
Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
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.

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
Sitei307 – 3082Cleavage Reviewed prediction
Binding sitei1110 – 11101ATP By similarity
Active sitei1204 – 12041Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1084 – 10929ATP 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
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
ProteomesiUP000001595: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 932908Extracellular Reviewed prediction
Add
BLAST
Transmembranei933 – 95523Helical; Reviewed prediction
Add
BLAST
Topological domaini956 – 1390435Cytoplasmic Reviewed prediction
Add
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 prediction
Add
BLAST
Chaini25 – 13901366Hepatocyte growth factor receptor
PRO_0000231600Add
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
Glycosylationi149 – 1491N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi172 ↔ 175 By similarity
Glycosylationi202 – 2021N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi298 ↔ 363 By similarity
Disulfide bondi385 ↔ 397 By similarity
Glycosylationi399 – 3991N-linked (GlcNAc...) Reviewed prediction
Glycosylationi405 – 4051N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi520 ↔ 538 By similarity
Disulfide bondi526 ↔ 561 By similarity
Disulfide bondi529 ↔ 545 By similarity
Disulfide bondi541 ↔ 551 By similarity
Glycosylationi607 – 6071N-linked (GlcNAc...) Reviewed prediction
Glycosylationi635 – 6351N-linked (GlcNAc...) Reviewed prediction
Glycosylationi785 – 7851N-linked (GlcNAc...) Reviewed prediction
Glycosylationi879 – 8791N-linked (GlcNAc...) Reviewed prediction
Glycosylationi930 – 9301N-linked (GlcNAc...) Reviewed prediction
Modified residuei977 – 9771Phosphothreonine By similarity
Modified residuei990 – 9901Phosphoserine By similarity
Modified residuei997 – 9971Phosphoserine By similarity
Modified residuei1000 – 10001Phosphoserine By similarity
Modified residuei1003 – 10031Phosphotyrosine By similarity
Modified residuei1230 – 12301Phosphotyrosine By similarity
Modified residuei1234 – 12341Phosphotyrosine; by autocatalysis By similarity
Modified residuei1235 – 12351Phosphotyrosine; by autocatalysis By similarity
Modified residuei1289 – 12891Phosphothreonine By similarity
Modified residuei1349 – 13491Phosphotyrosine; by autocatalysis By similarity
Modified residuei1356 – 13561Phosphotyrosine; by autocatalysis By similarity
Modified residuei1365 – 13651Phosphotyrosine By 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.
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-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.

Structurei

3D structure databases

ProteinModelPortaliQ2IBD8.
SMRiQ2IBD8. Positions 40-741, 1046-1346.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1212 – 1390179Interaction with RANBP9 By similarity
Add
BLAST
Regioni1320 – 135940Interaction with MUC20 By similarity
Add
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

HOVERGENiHBG006348.
InParanoidiQ2IBD8.
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.

Q2IBD8-1 [UniParc]FASTAAdd to Basket

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MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET     50
LIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD 100
CSSKANLSGG VWKDNINMAL VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH 150
TADIQSEVHC IFSPQIEEPS QCPDCVVSAL GAKVLSSVKD RFINFFVGNT 200
INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE FRDSYPIKYV 250
HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL 300
TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK 350
PDSAEPMDRS AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR 400
TLLRNSSGCE ARRDEYRTEF TTALQRVDLF MGQFSEVLLT SISTFIKGDL 450
TIANLGTSEG RFMQVVVSRS GPSTPHVNFL LDSHPVSPEV IVEHPLNQNG 500
YTLVVTGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW CHDKCVRSEE 550
CSSGTWTQQI CLPAIYKVFP SSAPLEGGTR LTICGWDFGF RRNNKFDLKK 600
TRVLLGNESC TLTLSESTMN ILKCTVGPAM NKHFNMSIII SNGHGTTQYS 650
TFSYVDPVIT GISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK 700
SVSNSILECY TPAQTISTEF AVKLKIDLAN RETSIFSYRE DPIVYEIHPT 750
KSFISGGSTI TGVGKNLNSV SVPRMVINVH EAGRNFTVAC QHRSNSEIIC 800
CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV FKPFEKPVMI 850
SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL 900
LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISIALLLLLG 950
FFLWLKKRKQ IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES 1000
VDYRATFPED QFPNSSQNGS CRQVQYPLTD MSPILTSGDS DISSPLLQNT 1050
VHIDLSALNP ELVQAVQHVV IGPSSLIVHF NEVIGRGHFG CVYHGTLLDN 1100
DGKKIHCAVK 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 HPKAEMRPSF SELVSRISAI FSTFIGEHYV 1350
HVNATYVNVK CVAPYPSLLS SEDNADDEVD TRPASFWETS 1390
Length:1,390
Mass (Da):155,480
Last modified:March 7, 2006 - v1
Checksum:i8010A9FD4E7809EB
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DP000026 Genomic DNA. Translation: ABC87460.1.
RefSeqiNP_001162038.1. NM_001168566.1.
UniGeneiPab.20121.

Genome annotation databases

GeneIDi100137030.
KEGGipon:100137030.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DP000026 Genomic DNA. Translation: ABC87460.1 .
RefSeqi NP_001162038.1. NM_001168566.1.
UniGenei Pab.20121.

3D structure databases

ProteinModelPortali Q2IBD8.
SMRi Q2IBD8. Positions 40-741, 1046-1346.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100137030.
KEGGi pon:100137030.

Organism-specific databases

CTDi 4233.

Phylogenomic databases

HOVERGENi HBG006348.
InParanoidi Q2IBD8.
KOi K05099.

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_PONAB
AccessioniPrimary (citable) accession number: Q2IBD8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: March 7, 2006
Last modified: June 11, 2014
This is version 76 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