EKS-HOS-00125

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00125

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Met	481.9	2.4E-144	1078	1338	261

Status

Reviewed

Ensembl Protein

ENSP00000380860

UniProt Accession

P08581; A1L467; B5A932; E7EQ94; O60366; Q12875; Q9UDX7; Q9UPL8;

Protein Name

Hepatocyte growth factor receptor

Protein Synonyms/Alias

HGF receptor; HGF/SF receptor; Proto-oncogene c-Met; Scatter factor receptor; SF receptor; Tyrosine-protein kinase Met;

Gene Name

MET

Gene Synonyms/Alias

MET;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000105976	ENSP00000445020	ENST00000539704
ENSG00000105976	ENSP00000398776	ENST00000422097
ENSG00000105976	ENSP00000380860	ENST00000397752
ENSG00000105976	ENSP00000317272	ENST00000318493
ENSG00000105976	ENSP00000400890	ENST00000437703
ENSG00000105976	ENSP00000398140	ENST00000454623
ENSG00000105976	ENSP00000413857	ENST00000456159
ENSG00000105976	ENSP00000410980	ENST00000436117

Organism

Homo sapiens

Functional Description

Receptor tyrosine kinase that transduces signals fromthe 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. Acts as a receptor for Listeria internalin inlB,mediating entry of the pathogen into cells.

Protein Length

1390

Protein Sequence
(FASTA)

MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH 60

HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD CSSKANLSGG VWKDNINMAL 120

VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 180

GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE 240

FRDSYPIKYV HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL 300

TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK PDSAEPMDRS 360

AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR TLLRNSSGCE ARRDEYRTEF 420

TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 480

LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 540

CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK 600

TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT 660

SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 720

AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV SVPRMVINVH 780

EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV 840

FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL 900

LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISTALLLLLG FFLWLKKRKQ 960

IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS 1020

CRQVQYPLTD MSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF 1080

NEVIGRGHFG CVYHGTLLDN DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL 1140

SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 1200

VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF 1260

TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 1320

HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD 1380

TRPASFWETS 1390

Nucleotide Sequence
(FASTA)

ATGAAGGCCC CCGCTGTGCT TGCACCTGGC ATCCTCGTGC TCCTGTTTAC CTTGGTGCAG 60

AGGAGCAATG GGGAGTGTAA AGAGGCACTA GCAAAGTCCG AGATGAATGT GAATATGAAG 120

TATCAGCTTC CCAACTTCAC CGCGGAAACA CCCATCCAGA ATGTCATTCT ACATGAGCAT 180

CACATTTTCC TTGGTGCCAC TAACTACATT TATGTTTTAA ATGAGGAAGA CCTTCAGAAG 240

GTTGCTGAGT ACAAGACTGG GCCTGTGCTG GAACACCCAG ATTGTTTCCC ATGTCAGGAC 300

TGCAGCAGCA AAGCCAATTT ATCAGGAGGT GTTTGGAAAG ATAACATCAA CATGGCTCTA 360

GTTGTCGACA CCTACTATGA TGATCAACTC ATTAGCTGTG GCAGCGTCAA CAGAGGGACC 420

TGCCAGCGAC ATGTCTTTCC CCACAATCAT ACTGCTGACA TACAGTCGGA GGTTCACTGC 480

ATATTCTCCC CACAGATAGA AGAGCCCAGC CAGTGTCCTG ACTGTGTGGT GAGCGCCCTG 540

GGAGCCAAAG TCCTTTCATC TGTAAAGGAC CGGTTCATCA ACTTCTTTGT AGGCAATACC 600

ATAAATTCTT CTTATTTCCC AGATCATCCA TTGCATTCGA TATCAGTGAG AAGGCTAAAG 660

GAAACGAAAG ATGGTTTTAT GTTTTTGACG GACCAGTCCT ACATTGATGT TTTACCTGAG 720

TTCAGAGATT CTTACCCCAT TAAGTATGTC CATGCCTTTG AAAGCAACAA TTTTATTTAC 780

TTCTTGACGG TCCAAAGGGA AACTCTAGAT GCTCAGACTT TTCACACAAG AATAATCAGG 840

TTCTGTTCCA TAAACTCTGG ATTGCATTCC TACATGGAAA TGCCTCTGGA GTGTATTCTC 900

ACAGAAAAGA GAAAAAAGAG ATCCACAAAG AAGGAAGTGT TTAATATACT TCAGGCTGCG 960

TATGTCAGCA AGCCTGGGGC CCAGCTTGCT AGACAAATAG GAGCCAGCCT GAATGATGAC 1020

ATTCTTTTCG GGGTGTTCGC ACAAAGCAAG CCAGATTCTG CCGAACCAAT GGATCGATCT 1080

GCCATGTGTG CATTCCCTAT CAAATATGTC AACGACTTCT TCAACAAGAT CGTCAACAAA 1140

AACAATGTGA GATGTCTCCA GCATTTTTAC GGACCCAATC ATGAGCACTG CTTTAATAGG 1200

ACACTTCTGA GAAATTCATC AGGCTGTGAA GCGCGCCGTG ATGAATATCG AACAGAGTTT 1260

ACCACAGCTT TGCAGCGCGT TGACTTATTC ATGGGTCAAT TCAGCGAAGT CCTCTTAACA 1320

TCTATATCCA CCTTCATTAA AGGAGACCTC ACCATAGCTA ATCTTGGGAC ATCAGAGGGT 1380

CGCTTCATGC AGGTTGTGGT TTCTCGATCA GGACCATCAA CCCCTCATGT GAATTTTCTC 1440

CTGGACTCCC ATCCAGTGTC TCCAGAAGTG ATTGTGGAGC ATACATTAAA CCAAAATGGC 1500

TACACACTGG TTATCACTGG GAAGAAGATC ACGAAGATCC CATTGAATGG CTTGGGCTGC 1560

AGACATTTCC AGTCCTGCAG TCAATGCCTC TCTGCCCCAC CCTTTGTTCA GTGTGGCTGG 1620

TGCCACGACA AATGTGTGCG ATCGGAGGAA TGCCTGAGCG GGACATGGAC TCAACAGATC 1680

TGTCTGCCTG CAATCTACAA GGTTTTCCCA AATAGTGCAC CCCTTGAAGG AGGGACAAGG 1740

CTGACCATAT GTGGCTGGGA CTTTGGATTT CGGAGGAATA ATAAATTTGA TTTAAAGAAA 1800

ACTAGAGTTC TCCTTGGAAA TGAGAGCTGC ACCTTGACTT TAAGTGAGAG CACGATGAAT 1860

ACATTGAAAT GCACAGTTGG TCCTGCCATG AATAAGCATT TCAATATGTC CATAATTATT 1920

TCAAATGGCC ACGGGACAAC ACAATACAGT ACATTCTCCT ATGTGGATCC TGTAATAACA 1980

AGTATTTCGC CGAAATACGG TCCTATGGCT GGTGGCACTT TACTTACTTT AACTGGAAAT 2040

TACCTAAACA GTGGGAATTC TAGACACATT TCAATTGGTG GAAAAACATG TACTTTAAAA 2100

AGTGTGTCAA ACAGTATTCT TGAATGTTAT ACCCCAGCCC AAACCATTTC AACTGAGTTT 2160

GCTGTTAAAT TGAAAATTGA CTTAGCCAAC CGAGAGACAA GCATCTTCAG TTACCGTGAA 2220

GATCCCATTG TCTATGAAAT TCATCCAACC AAATCTTTTA TTAGTGGTGG GAGCACAATA 2280

ACAGGTGTTG GGAAAAACCT GAATTCAGTT AGTGTCCCGA GAATGGTCAT AAATGTGCAT 2340

GAAGCAGGAA GGAACTTTAC AGTGGCATGT CAACATCGCT CTAATTCAGA GATAATCTGT 2400

TGTACCACTC CTTCCCTGCA ACAGCTGAAT CTGCAACTCC CCCTGAAAAC CAAAGCCTTT 2460

TTCATGTTAG ATGGGATCCT TTCCAAATAC TTTGATCTCA TTTATGTACA TAATCCTGTG 2520

TTTAAGCCTT TTGAAAAGCC AGTGATGATC TCAATGGGCA ATGAAAATGT ACTGGAAATT 2580

AAGGGAAATG ATATTGACCC TGAAGCAGTT AAAGGTGAAG TGTTAAAAGT TGGAAATAAG 2640

AGCTGTGAGA ATATACACTT ACATTCTGAA GCCGTTTTAT GCACGGTCCC CAATGACCTG 2700

CTGAAATTGA ACAGCGAGCT AAATATAGAG TGGAAGCAAG CAATTTCTTC AACCGTCCTT 2760

GGAAAAGTAA TAGTTCAACC AGATCAGAAT TTCACAGGAT TGATTGCTGG TGTTGTCTCA 2820

ATATCAACAG CACTGTTATT ACTACTTGGG TTTTTCCTGT GGCTGAAAAA GAGAAAGCAA 2880

ATTAAAGATC TGGGCAGTGA ATTAGTTCGC TACGATGCAA GAGTACACAC TCCTCATTTG 2940

GATAGGCTTG TAAGTGCCCG AAGTGTAAGC CCAACTACAG AAATGGTTTC AAATGAATCT 3000

GTAGACTACC GAGCTACTTT TCCAGAAGAT CAGTTTCCTA ATTCATCTCA GAACGGTTCA 3060

TGCCGACAAG TGCAGTATCC TCTGACAGAC ATGTCCCCCA TCCTAACTAG TGGGGACTCT 3120

GATATATCCA GTCCATTACT GCAAAATACT GTCCACATTG ACCTCAGTGC TCTAAATCCA 3180

GAGCTGGTCC AGGCAGTGCA GCATGTAGTG ATTGGGCCCA GTAGCCTGAT TGTGCATTTC 3240

AATGAAGTCA TAGGAAGAGG GCATTTTGGT TGTGTATATC ATGGGACTTT GTTGGACAAT 3300

GATGGCAAGA AAATTCACTG TGCTGTGAAA TCCTTGAACA GAATCACTGA CATAGGAGAA 3360

GTTTCCCAAT TTCTGACCGA GGGAATCATC ATGAAAGATT TTAGTCATCC CAATGTCCTC 3420

TCGCTCCTGG GAATCTGCCT GCGAAGTGAA GGGTCTCCGC TGGTGGTCCT ACCATACATG 3480

AAACATGGAG ATCTTCGAAA TTTCATTCGA AATGAGACTC ATAATCCAAC TGTAAAAGAT 3540

CTTATTGGCT TTGGTCTTCA AGTAGCCAAA GGCATGAAAT ATCTTGCAAG CAAAAAGTTT 3600

GTCCACAGAG ACTTGGCTGC AAGAAACTGT ATGCTGGATG AAAAATTCAC AGTCAAGGTT 3660

GCTGATTTTG GTCTTGCCAG AGACATGTAT GATAAAGAAT ACTATAGTGT ACACAACAAA 3720

ACAGGTGCAA AGCTGCCAGT GAAGTGGATG GCTTTGGAAA GTCTGCAAAC TCAAAAGTTT 3780

ACCACCAAGT CAGATGTGTG GTCCTTTGGC GTGCTCCTCT GGGAGCTGAT GACAAGAGGA 3840

GCCCCACCTT ATCCTGACGT AAACACCTTT GATATAACTG TTTACTTGTT GCAAGGGAGA 3900

AGACTCCTAC AACCCGAATA CTGCCCAGAC CCCTTATATG AAGTAATGCT AAAATGCTGG 3960

CACCCTAAAG CCGAAATGCG CCCATCCTTT TCTGAACTGG TGTCCCGGAT ATCAGCGATC 4020

TTCTCTACTT TCATTGGGGA GCACTATGTC CATGTGAACG CTACTTATGT GAACGTAAAA 4080

TGTGTCGCTC CGTATCCTTC TCTGTTGTCA TCAGAAGATA ACGCTGATGA TGAGGTGGAC 4140

ACACGACCAG CCTCCTTCTG GGAGACATCA TAG 4173

Domain Profile

S: 1     vdkeeviGkGhfGvvykgelsdsaskkikvavksleritdiekveeflreglvmkeldhp  60

         v+++eviG+GhfG+vy+g+l+d+++kki++avksl+ritdi++v++fl+eg++mk+++hp

Q: 1078  VHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHP  1137

         799*********************************************************

S: 61    nvlsllGialddeglplvvlpymkkGdlksfirneernltvkdllefalqvakgmeylas  120

         nvlsllGi+l++eg+plvvlpymk+Gdl++firne++n+tvkdl++f+lqvakgm+ylas

Q: 1138  NVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLAS  1197

         ************************************************************

S: 121   kkfvhrdlaarnclldekltvkvadfGlardvldkelyvveeerdarlpvkwlaleslqt  180

         kkfvhrdlaarnc+ldek+tvkvadfGlard++dke+y+v+++++a+lpvkw+aleslqt

Q: 1198  KKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQT  1257

         ************************************************************

S: 181   fkqfttksdvwsfGvllwelltrgatpysevasfdltlylkegrrlrkpeycpdklydvm  240

         +k fttksdvwsfGvllwel+trga+py++v++fd+t+yl +grrl +peycpd ly+vm

Q: 1258  QK-FTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVM  1316

         **.*********************************************************

S: 241   lkcwkakpaerpqfsdlvsiis  262

         lkcw++k+++rp+fs+lvs+is

Q: 1317  LKCWHPKAEMRPSFSELVSRIS  1338

         ********************98

Domain Sequence
(FASTA)

VHFNEVIGRG HFGCVYHGTL LDNDGKKIHC AVKSLNRITD IGEVSQFLTE GIIMKDFSHP 60

NVLSLLGICL RSEGSPLVVL PYMKHGDLRN FIRNETHNPT VKDLIGFGLQ VAKGMKYLAS 120

KKFVHRDLAA RNCMLDEKFT VKVADFGLAR DMYDKEYYSV HNKTGAKLPV KWMALESLQT 180

QKFTTKSDVW SFGVLLWELM TRGAPPYPDV NTFDITVYLL QGRRLLQPEY CPDPLYEVML 240

KCWHPKAEMR PSFSELVSRI S 261

Keyword

3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0009925	; C:basal plasma membrane
GO:0005737	; C:cytoplasm
GO:0060076	; C:excitatory synapse
GO:0005615	; C:extracellular space
GO:0019861	; C:flagellum
GO:0005887	; C:integral to plasma membrane
GO:0043025	; C:neuronal cell body
GO:0014069	; C:postsynaptic density
GO:0045211	; C:postsynaptic membrane
GO:0005524	; F:ATP binding
GO:0005008	; F:hepatocyte growth factor-activated receptor activity
GO:0000187	; P:activation of MAPK activity
GO:0030534	; P:adult behavior
GO:0007411	; P:axon guidance
GO:0007420	; P:brain development
GO:0048754	; P:branching morphogenesis of a tube
GO:0007569	; P:cell aging
GO:0008283	; P:cell proliferation
GO:0071243	; P:cellular response to arsenic-containing substance
GO:0071333	; P:cellular response to glucose stimulus
GO:0071363	; P:cellular response to growth factor stimulus
GO:0071354	; P:cellular response to interleukin-6
GO:0071375	; P:cellular response to peptide hormone stimulus
GO:0021953	; P:central nervous system neuron differentiation
GO:0007595	; P:lactation
GO:0001889	; P:liver development
GO:0008584	; P:male gonad development
GO:0014812	; P:muscle cell migration
GO:0051450	; P:myoblast proliferation
GO:0014902	; P:myotube differentiation
GO:1901299	; P:negative regulation of hydrogen peroxide-mediated programmed cell death
GO:0010801	; P:negative regulation of peptidyl-threonine phosphorylation
GO:0001764	; P:neuron migration
GO:0014003	; P:oligodendrocyte development
GO:0031016	; P:pancreas development
GO:0001890	; P:placenta development
GO:0050775	; P:positive regulation of dendrite morphogenesis
GO:0045740	; P:positive regulation of DNA replication
GO:0010628	; P:positive regulation of gene expression
GO:0010828	; P:positive regulation of glucose transport
GO:0045840	; P:positive regulation of mitosis
GO:0010976	; P:positive regulation of neuron projection development
GO:0033138	; P:positive regulation of peptidyl-serine phosphorylation
GO:0010800	; P:positive regulation of peptidyl-threonine phosphorylation
GO:0046777	; P:protein autophosphorylation
GO:0060665	; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling
GO:0001101	; P:response to acid
GO:0042493	; P:response to drug
GO:0014070	; P:response to organic cyclic compound
GO:0009611	; P:response to wounding
GO:0030317	; P:sperm motility

KEGG

hsa:4233

;

InterPros

IPR013783	; Ig-like_fold.
IPR014756	; Ig_E-set.
IPR002909	; IPT_TIG_rcpt.
IPR011009	; Kinase-like_dom.
IPR003659	; Plexin-like.
IPR016201	; Plexin-like_fold.
IPR002165	; Plexin_repeat.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR001627	; Semaphorin/CD100_Ag.
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.

Pfam

PF07714	; Pkinase_Tyr; 1.
PF01437	; PSI; 1.
PF01403	; Sema; 1.
PF01833	; TIG; 3.

SMARTs

SM00429	; IPT; 4.
SM00423	; PSI; 1.
SM00630	; Sema; 1.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS51004	; SEMA; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013