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P97523 (MET_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte growth factor receptor

Short name=HGF receptor
EC=2.7.10.1
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name=SF receptor
Tyrosine-protein kinase Met
Gene names
Name:Met
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1382 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Enzyme regulation

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.

Subunit structure

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 By similarity. 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.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed at highest levels in lung, liver and kidney, also expressed in stomach, intestine, spleen, testis and brain. Not expressed in heart or muscle.

Developmental stage

Expression is down-regulated during pregnancy and is virtually undetectable during lactation. Expression progressively increases post-lactation.

Induction

By interleukin-6 and acute acid-induced gastric injury. Inhibited by prolactin.

Domain

The kinase domain is involved in SPSB1 binding By similarity.

The beta-propeller Sema domain mediates binding to HGF By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 3 IPT/TIG domains.

Contains 1 protein kinase domain.

Contains 1 Sema domain.

Ontologies

Keywords
   Cellular componentMembrane
   DiseaseProto-oncogene
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Inferred from expression pattern PubMed 12106690. Source: RGD

cell aging

Inferred from expression pattern PubMed 18202313. Source: RGD

cellular response to arsenic-containing substance

Inferred from expression pattern PubMed 16876216. Source: RGD

cellular response to glucose stimulus

Inferred from expression pattern PubMed 17124385. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern PubMed 7526865. Source: RGD

cellular response to inorganic substance

Inferred from expression pattern PubMed 12839939. Source: RGD

cellular response to interleukin-6

Inferred from expression pattern Ref.2. Source: RGD

cellular response to peptide hormone stimulus

Inferred from expression pattern PubMed 17035232. Source: RGD

central nervous system neuron differentiation

Inferred from expression pattern PubMed 18262389. Source: RGD

hepatocyte growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 18262389. Source: GOC

lactation

Inferred from expression pattern Ref.4. Source: RGD

liver development

Inferred from expression pattern PubMed 8506951. Source: RGD

male gonad development

Inferred from expression pattern PubMed 11316747. Source: RGD

negative regulation of peptidyl-threonine phosphorylation

Inferred from mutant phenotype PubMed 18262389. Source: RGD

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17427161. Source: RGD

neuron migration

Inferred from direct assay PubMed 12106690. Source: RGD

oligodendrocyte development

Inferred from expression pattern PubMed 17382307. Source: RGD

pancreas development

Inferred from expression pattern PubMed 8954115. Source: RGD

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 7499789. Source: GOC

positive regulation of DNA replication

Inferred from mutant phenotype PubMed 17427161. Source: RGD

positive regulation of dendrite morphogenesis

Inferred from mutant phenotype PubMed 18262389. Source: RGD

positive regulation of endothelial cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from mutant phenotype PubMed 18262389. Source: RGD

positive regulation of mitosis

Inferred from mutant phenotype PubMed 17427161. Source: RGD

positive regulation of neuron projection development

Inferred from mutant phenotype PubMed 18262389. Source: RGD

positive regulation of peptidyl-serine phosphorylation

Inferred from mutant phenotype PubMed 18262389. Source: RGD

positive regulation of peptidyl-threonine phosphorylation

Inferred from mutant phenotype PubMed 18262389. Source: RGD

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17427161. Source: RGD

protein autophosphorylation

Inferred from direct assay PubMed 7499789PubMed 8208547. Source: RGD

response to acid

Inferred from expression pattern PubMed 7729276. Source: RGD

response to drug

Inferred from expression pattern PubMed 18652820. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 19638569. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 17412609. Source: RGD

response to wounding

Inferred from expression pattern PubMed 19213039. Source: RGD

sperm motility

Inferred from mutant phenotype PubMed 12399538. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 18794800. Source: RGD

dendrite

Inferred from direct assay PubMed 17230549. Source: RGD

excitatory synapse

Inferred from direct assay PubMed 16861928. Source: RGD

extracellular space

Inferred from direct assay PubMed 19794968. Source: RGD

integral component of membrane

Non-traceable author statement Ref.2. Source: RGD

neuron projection

Inferred from direct assay PubMed 18262389. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 16861928. Source: RGD

plasma membrane

Inferred from direct assay PubMed 18202313. Source: RGD

postsynaptic density

Inferred from direct assay PubMed 16861928. Source: RGD

postsynaptic membrane

Inferred from direct assay PubMed 16861928. Source: RGD

sperm flagellum

Inferred from direct assay PubMed 12399538. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

beta-catenin binding

Inferred from physical interaction PubMed 16952352. Source: RGD

hepatocyte growth factor-activated receptor activity

Inferred from mutant phenotype PubMed 18262389. Source: RGD

phosphatidylinositol 3-kinase binding

Inferred from direct assay PubMed 7499789. Source: RGD

phospholipase binding

Inferred from physical interaction PubMed 7499789. Source: RGD

protein complex binding

Inferred from direct assay PubMed 17065554. Source: RGD

protein heterodimerization activity

Inferred from direct assay PubMed 8833090. Source: RGD

protein tyrosine kinase activity

Inferred from direct assay PubMed 7499789. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 13821358Hepatocyte growth factor receptor
PRO_0000024442

Regions

Topological domain25 – 935911Extracellular Potential
Transmembrane936 – 95621Helical; Potential
Topological domain957 – 1379423Cytoplasmic Potential
Domain27 – 516490Sema
Domain564 – 65693IPT/TIG 1
Domain658 – 74083IPT/TIG 2
Domain743 – 83795IPT/TIG 3
Domain1079 – 1346268Protein kinase
Nucleotide binding1085 – 10939ATP By similarity
Region1213 – 1382170Interaction with RANBP9 By similarity
Region1321 – 136040Interaction with MUC20 By similarity

Sites

Active site12051Proton acceptor By similarity
Binding site11111ATP By similarity
Site308 – 3092Cleavage Potential

Amino acid modifications

Modified residue9781Phosphothreonine By similarity
Modified residue9911Phosphoserine By similarity
Modified residue9981Phosphoserine By similarity
Modified residue10011Phosphoserine By similarity
Modified residue10041Phosphotyrosine By similarity
Modified residue12311Phosphotyrosine By similarity
Modified residue12351Phosphotyrosine; by autocatalysis By similarity
Modified residue12361Phosphotyrosine; by autocatalysis By similarity
Modified residue12901Phosphothreonine By similarity
Modified residue13501Phosphotyrosine; by autocatalysis By similarity
Modified residue13571Phosphotyrosine; by autocatalysis By similarity
Modified residue13661Phosphotyrosine By similarity
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation3591N-linked (GlcNAc...) Potential
Glycosylation4001N-linked (GlcNAc...) Potential
Glycosylation4061N-linked (GlcNAc...) Potential
Glycosylation6081N-linked (GlcNAc...) Potential
Glycosylation6361N-linked (GlcNAc...) Potential
Glycosylation7861N-linked (GlcNAc...) Potential
Glycosylation8801N-linked (GlcNAc...) Potential
Disulfide bond95 ↔ 101 By similarity
Disulfide bond98 ↔ 160 By similarity
Disulfide bond133 ↔ 141 By similarity
Disulfide bond173 ↔ 176 By similarity
Disulfide bond299 ↔ 364 By similarity
Disulfide bond386 ↔ 398 By similarity
Disulfide bond521 ↔ 539 By similarity
Disulfide bond527 ↔ 562 By similarity
Disulfide bond530 ↔ 546 By similarity
Disulfide bond542 ↔ 552 By similarity

Experimental info

Sequence conflict531H → Q in AAB19189. Ref.2
Sequence conflict581P → H in AAB19189. Ref.2
Sequence conflict2401P → G in AAB19189. Ref.2
Sequence conflict4271R → A in AAB19189. Ref.2
Sequence conflict4851Y → H in AAB19189. Ref.2
Sequence conflict490 – 4956EVIVEH → GAAGIR Ref.3
Sequence conflict5331P → A in AAB19189. Ref.2
Sequence conflict7401R → G in AAB19189. Ref.2
Sequence conflict7441V → F in AAB19189. Ref.2
Sequence conflict8081R → Q in AAB19189. Ref.2
Sequence conflict890 – 8934SEAL → TASV in CAA86508. Ref.4
Sequence conflict9071Missing in CAA86508. Ref.4
Sequence conflict9241K → E in CAA86508. Ref.4
Sequence conflict9341A → R in CAA86508. Ref.4
Sequence conflict10281L → P in AAB19189. Ref.2
Sequence conflict10681P → Q in AAB19189. Ref.2
Sequence conflict11971V → A Ref.2
Sequence conflict11971V → A Ref.5
Sequence conflict13311V → F in AAB19189. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P97523 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 66B8F2C88FE34427

FASTA1,382153,941
        10         20         30         40         50         60 
MKAPTALAPG ILLLLLTLAQ RSHGECKEAL VKSEMNVNMK YQLPNFTAET PIHNVVLPGH 

        70         80         90        100        110        120 
HIYLGATNYI YVLNDKDLQK VSEFKTGPVV EHPDCFPCQD CSSKANVSGG VWKDNVNMAL 

       130        140        150        160        170        180 
LVDTYYDDQL ISCGSVNRGT CQRHVLPPDN AADIQSEVHC MFSPLAEEES GQCPDCVVSA 

       190        200        210        220        230        240 
LGAKVLLSEK DRFINFFVGN TINSSYPPDY SLHSISVRRL KETQDGFKFL TDQSYIDVLP 

       250        260        270        280        290        300 
EFRDSYPIKY IHAFESNHFI YFLTVQKETL DAQTFHTRII RFCSVDSGLH SYMEMPLECI 

       310        320        330        340        350        360 
LTEKRRKRST REEVFNILQA AYVSKPGANL AKQIGASPYD DILYGVFAQS KPDSAEPMNR 

       370        380        390        400        410        420 
SAVCAFPIKY VNDFFNKIVN KNNVRCLQHF YGPNHEHCFN RTLLRNSSGC EVRSDEYRTE 

       430        440        450        460        470        480 
FTTALQRVDL FMGRLNHVLL TSISTFIKGD LTIANLGTSE GRFMQVVLSR TAHFTPHVNF 

       490        500        510        520        530        540 
LLDSYPVSPE VIVEHPSNQN GYTLVVTGKK ITKIPLNGLG CGHFQSCSQC LSPPYFIQCG 

       550        560        570        580        590        600 
WCHNRCVHSN ECPSGTWTQE ICLPAVYKVF PTSAPLEGGT MLTICGWDFG FKKNNKFDLR 

       610        620        630        640        650        660 
KTKVLLGNES CTLTLSESTT NTLKCTVGPA MSEHFNVSVI VSNSRETTQY SAFSYVDPVI 

       670        680        690        700        710        720 
TSISPRYGPH AGGTLLTLTG KYLNSGNSRH ISIGGKTCTL KSVSDSILEC YTPGHTVSAE 

       730        740        750        760        770        780 
FPVKLKIDLA DRVTSSFSYR EDPVVSEIHP TKSFISGGST ITGIGKNLNS VSTPKLVIEV 

       790        800        810        820        830        840 
HDVGVNYTVA CQHRSSSEII CCTTPSLRQL DLQLPLKTKA FFLLDGILSK HFDLTYVHDP 

       850        860        870        880        890        900 
MFKPFEKPVM ISMGNENVVE IKGDDIDPEA VKGEVLKVGN KSCENLHWHS EALLCTVPSD 

       910        920        930        940        950        960 
LLKLNGGELN IEWKQAVSST VLGKVIVQPD QNFAGLIIGA VSISVVVLLV SGLFLWLRKR 

       970        980        990       1000       1010       1020 
KHKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE SVDYRATFPE DQFPNSSQNG 

      1030       1040       1050       1060       1070       1080 
ACRQVQYLLT DLSPILTSGD SDISSPLLQN TVHIDLSALN PELVQAVPHV VIGPSSLIVH 

      1090       1100       1110       1120       1130       1140 
FNEVIGRGHF GCVYHGTLLD SDGKKIHCAV KSLNRITDIE EVSQFLTEGI IMKDFSHPNV 

      1150       1160       1170       1180       1190       1200 
LSLLGICLRS EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLVSKK 

      1210       1220       1230       1240       1250       1260 
FVHRDLAARN CMLDEKFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW MALESLQTQK 

      1270       1280       1290       1300       1310       1320 
FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITIYLLQG RRLLQPEYCP DALYEVMLKC 

      1330       1340       1350       1360       1370       1380 
WHPKAEMRPS VSELVSRISS IFSTFIGEHY VHVNATYVNV KCVAPYPSLL PSQDNIDGEA 


NT 

« Hide

References

[1]"Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA."
Wallenius V.R., Rawet H., Skrtic S., Helou K., Qiu Y., Levan G., Ekberg S., Carlsson B., Isaksson O.G.P., Nakamura T., Jansson J.-O.
Mamm. Genome 8:661-667(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Liver.
[2]"Primary structure of rat HGF receptor and induced expression in glomerular mesangial cells."
Liu Y., Tolbert E.M., Sun A.M., Dworkin L.D.
Am. J. Physiol. 271:F679-F688(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Strain: Sprague-Dawley.
Tissue: Kidney.
[3]"Increased expression of c-met messenger RNA following acute gastric injury in rats."
Tsujii M., Kawano S., Tsuji S., Ito T., Hayashi N., Horimoto M., Mita E., Nagano K., Masuda E., Hayashi N., Fusamoto H., Kamada T.
Biochem. Biophys. Res. Commun. 200:536-541(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 364-495.
Strain: Sprague-Dawley.
Tissue: Gastric mucosa.
[4]"Modulation of hepatocyte growth factor and c-met in the rat mammary gland during pregnancy, lactation, and involution."
Pepper M.S., Soriano J.V., Menoud P.-A., Sappino A.-P., Orci L., Montesano R.
Exp. Cell Res. 219:204-210(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 851-1002.
Tissue: Intestine.
[5]Kikuchi Y.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1129-1267.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X96786 mRNA. Translation: CAA65582.1.
U65007 mRNA. Translation: AAB19189.1.
S69881 mRNA. Translation: AAB30575.1.
Z46374 mRNA. Translation: CAA86508.1.
AB012281 Genomic DNA. Translation: BAA28171.1.
PIRPC2131.
RefSeqNP_113705.1. NM_031517.2.
UniGeneRn.10617.

3D structure databases

ProteinModelPortalP97523.
SMRP97523. Positions 40-742, 1047-1347.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP97523.

Proteomic databases

PaxDbP97523.
PRIDEP97523.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24553.
KEGGrno:24553.
UCSCRGD:3082. rat.

Organism-specific databases

CTD4233.
RGD3082. Met.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000220900.
HOVERGENHBG006348.
InParanoidP97523.
KOK05099.
PhylomeDBP97523.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.

Gene expression databases

GenevestigatorP97523.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProIPR013783. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio603662.
PROP97523.

Entry information

Entry nameMET_RAT
AccessionPrimary (citable) accession number: P97523
Secondary accession number(s): P97579, Q63119, Q63964
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families