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Q108U6 (MET_LOXAF) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 67. 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
OrganismLoxodonta africana (African elephant) [Reference proteome]
Taxonomic identifier9785 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaAfrotheriaProboscideaElephantidaeLoxodonta

Protein attributes

Sequence length1382 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceInferred from homology

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. 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 By similarity.

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_processactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

adult behavior

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

branching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

muscle cell migration

Inferred from electronic annotation. Source: Ensembl

myoblast proliferation

Inferred from electronic annotation. Source: Ensembl

myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of hydrogen peroxide-mediated programmed cell death

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from electronic annotation. Source: Ensembl

positive chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling

Inferred from electronic annotation. Source: Ensembl

semaphorin-plexin signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasal plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

hepatocyte growth factor-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 13821358Hepatocyte growth factor receptor
PRO_0000250465

Regions

Topological domain25 – 935911Extracellular Potential
Transmembrane936 – 95621Helical; Potential
Topological domain957 – 1382426Cytoplasmic 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
Glycosylation4501N-linked (GlcNAc...) Potential
Glycosylation6081N-linked (GlcNAc...) Potential
Glycosylation6361N-linked (GlcNAc...) Potential
Glycosylation7511N-linked (GlcNAc...) Potential
Glycosylation7861N-linked (GlcNAc...) Potential
Glycosylation8801N-linked (GlcNAc...) Potential
Glycosylation9311N-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

Sequences

Sequence LengthMass (Da)Tools
Q108U6 [UniParc].

Last modified August 22, 2006. Version 1.
Checksum: B22F334F1CC126BC

FASTA1,382154,684
        10         20         30         40         50         60 
MKAPAVLAPG VLVLLFTLVR KSHGECEEAL AKSKMNVNMK YQLPNFTADT PIQNVVLHEH 

        70         80         90        100        110        120 
HIFLGAINNI YVLNDKDLQK VAEYKTGPVL EHPDCLPCQD CSSKANLSGS VWKDNINMAL 

       130        140        150        160        170        180 
LVDTYYDDQL ITCGSVNRGT CQRHVLPPDN PADIHSKVHC MYSPQADEEP SKCPDCVVSA 

       190        200        210        220        230        240 
LGTKVLLTEK DRFINFFVGN TVNSSYLPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP 

       250        260        270        280        290        300 
EFRDSYPIKY VHAFKHNQFI YFLTVQRETL ESQTFHTRII RFCSVDSGLH SYMEMPLECI 

       310        320        330        340        350        360 
LTEKRRKRSA REEVFNILQA AYVSKPGAYL AKQIGALPDD DILYGVFAQS KLDSAEPMNR 

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

       430        440        450        460        470        480 
FTTALQRVDL FTGQFNQVLL TSISTFIKGN LTIANLGTSE GRFMQVVVSR SGLTTPHVNF 

       490        500        510        520        530        540 
RLDSHAVSPE VILEHPLNQN GYTLVITGKK ITKIPLDGLG CDHFQSCSQC LSAPSFVQCG 

       550        560        570        580        590        600 
WCHNKCARAE ECPNGMWTQE ICLPTIYEVF PTSAPLEGGT TLTVCGWDFG FRRNNKFDLK 

       610        620        630        640        650        660 
KTRVLIGNDS CTLTLSESTT NTLKCTVGPA MNKHFNLSII ISNGRGTARY RTFSYVEPVI 

       670        680        690        700        710        720 
TSISPSYGPK AGGTLVTLTG KYLNSGNSRH ISIGGKTCTL KSVSDSVLEC YTPAQSISTD 

       730        740        750        760        770        780 
FPVKLKIDLA NREAYSFSYQ EDPTVYEIHP NKSFISGGST ITGIGKNLNS VSVPRMVINV 

       790        800        810        820        830        840 
QEAGRNFTVA CQHRSNSEII CCTTPSLQQL NLQLPLKTKA FFMLDGIHSN YFDLIYVHNP 

       850        860        870        880        890        900 
VFKPFKKPVM ISMGNENVLE IKGDYIDPEA VKGEVLKVGN KSCENIHLQS EAVLCTVPND 

       910        920        930        940        950        960 
LLKLNSELNI EWKQAVSSTV LGKVIVQPDQ NFTGLIVGVV SISIILLLLL GLFLWLKKRK 

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

      1030       1040       1050       1060       1070       1080 
SCRQVQYPLT DMSPILTNGD SDSSIPLLQN NVHIDLSALN PELVQAVQHV VIGPSSLIVH 

      1090       1100       1110       1120       1130       1140 
FNEVIGRGHF GCVYHGTLLD NGDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV 

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

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

      1270       1280       1290       1300       1310       1320 
FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG RRLLQPEYCP DPLYEVMLKC 

      1330       1340       1350       1360       1370       1380 
WHPKAEMRPS FSELVSRISA IFSTFIGEHY VHVNTTYVNV KCVAPYPSLL SSQDSVDDEV 


DT 

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DP000087 Genomic DNA. Translation: ABG66646.1.
RefSeqXP_003407277.1. XM_003407229.1.

3D structure databases

ProteinModelPortalQ108U6.
SMRQ108U6. Positions 40-742, 1047-1347.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100656285.

Phylogenomic databases

HOGENOMHOG000220900.
HOVERGENHBG006348.

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...

Entry information

Entry nameMET_LOXAF
AccessionPrimary (citable) accession number: Q108U6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: August 22, 2006
Last modified: June 11, 2014
This is version 67 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