EKS-HOS-00281
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-HOS-00281
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
TKL/STKR467.96.1E-140128415288
StatusReviewed
Ensembl ProteinENSP00000364129
UniProt AccessionP36897; Q6IR47; Q706C0; Q706C1;
Protein NameTGF-beta receptor type-1
Protein Synonyms/Alias TGFR-1; Activin A receptor type II-like protein kinase of 53kD; Activin receptor-like kinase 5; ALK-5; ALK5; Serine/threonine-protein kinase receptor R4; SKR4; TGF-beta type I receptor; Transforming growth factor-beta receptor type I; TGF-beta receptor type I; TbetaR-I;
Gene NameTGFBR1
Gene Synonyms/Alias TGFBR1; ALK5, SKR4;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSG00000106799ENSP00000447707ENST00000546584
ENSG00000106799ENSP00000446685ENST00000549766
ENSG00000106799ENSP00000449934ENST00000547314
ENSG00000106799ENSP00000364133ENST00000374994
ENSG00000106799ENSP00000450052ENST00000550253
ENSG00000106799ENSP00000447182ENST00000552573
ENSG00000106799ENSP00000364129ENST00000374990
ENSG00000106799ENSP00000449028ENST00000549021
ENSG00000106799ENSP00000447297ENST00000552516
ENSG00000106799ENSP00000448518ENST00000548365
OrganismHomo sapiens
Functional DescriptionTransmembrane serine/threonine kinase forming with theTGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non- canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.
Protein Length426
Protein Sequence
(FASTA)
MEAAVAAPRP RLLLLVLAAA AAAAAALLPG ATALQCFCHL CTKDNFTCVT DGLCFVSVTE 60
TTDKVIHNSM CIAEIDLIPR DRPFVCAPSS KTGSVTTTYC CNQDHCNKIE LPTTGLPLLV 120
QRTIARTIVL QESIGKGRFG EVWRGKWRGE EVAVKIFSSR EERSWFREAE IYQTVMLRHE 180
NILGFIAADN KDNGTWTQLW LVSDYHEHGS LFDYLNRYTV TVEGMIKLAL STASGLAHLH 240
MEIVGTQGKP AIAHRDLKSK NILVKKNGTC CIADLGLAVR HDSATDTIDI APNHRVGTKR 300
YMAPEVLDDS INMKHFESFK RADIYAMGLV FWEIARRCSI GGIHEDYQLP YYDLVPSDPS 360
VEEMRKVVCE QKLRPNIPNR WQSCEALRVM AKIMRECWYA NGAARLTALR IKKTLSQLSQ 420
QEGIKM 426
Nucleotide Sequence
(FASTA)
ATGGAGGCGG CGGTCGCTGC TCCGCGTCCC CGGCTGCTCC TCCTCGTGCT GGCGGCGGCG 60
GCGGCGGCGG CGGCGGCGCT GCTCCCGGGG GCGACGGCGT TACAGTGTTT CTGCCACCTC 120
TGTACAAAAG ACAATTTTAC TTGTGTGACA GATGGGCTCT GCTTTGTCTC TGTCACAGAG 180
ACCACAGACA AAGTTATACA CAACAGCATG TGTATAGCTG AAATTGACTT AATTCCTCGA 240
GATAGGCCGT TTGTATGTGC ACCCTCTTCA AAAACTGGGT CTGTGACTAC AACATATTGC 300
TGCAATCAGG ACCATTGCAA TAAAATAGAA CTTCCAACTA CTGGTTTACC ATTGCTTGTT 360
CAGAGAACAA TTGCGAGAAC TATTGTGTTA CAAGAAAGCA TTGGCAAAGG TCGATTTGGA 420
GAAGTTTGGA GAGGAAAGTG GCGGGGAGAA GAAGTTGCTG TTAAGATATT CTCCTCTAGA 480
GAAGAACGTT CGTGGTTCCG TGAGGCAGAG ATTTATCAAA CTGTAATGTT ACGTCATGAA 540
AACATCCTGG GATTTATAGC AGCAGACAAT AAAGACAATG GTACTTGGAC TCAGCTCTGG 600
TTGGTGTCAG ATTATCATGA GCATGGATCC CTTTTTGATT ACTTAAACAG ATACACAGTT 660
ACTGTGGAAG GAATGATAAA ACTTGCTCTG TCCACGGCGA GCGGTCTTGC CCATCTTCAC 720
ATGGAGATTG TTGGTACCCA AGGAAAGCCA GCCATTGCTC ATAGAGATTT GAAATCAAAG 780
AATATCTTGG TAAAGAAGAA TGGAACTTGC TGTATTGCAG ACTTAGGACT GGCAGTAAGA 840
CATGATTCAG CCACAGATAC CATTGATATT GCTCCAAACC ACAGAGTGGG AACAAAAAGG 900
TACATGGCCC CTGAAGTTCT CGATGATTCC ATAAATATGA AACATTTTGA ATCCTTCAAA 960
CGTGCTGACA TCTATGCAAT GGGCTTAGTA TTCTGGGAAA TTGCTCGACG ATGTTCCATT 1020
GGTGGAATTC ATGAAGATTA CCAACTGCCT TATTATGATC TTGTACCTTC TGACCCATCA 1080
GTTGAAGAAA TGAGAAAAGT TGTTTGTGAA CAGAAGTTAA GGCCAAATAT CCCAAACAGA 1140
TGGCAGAGCT GTGAAGCCTT GAGAGTAATG GCTAAAATTA TGAGAGAATG TTGGTATGCC 1200
AATGGAGCAG CTAGGCTTAC AGCATTGCGG ATTAAGAAAA CATTATCGCA ACTCAGTCAA 1260
CAGGAAGGCA TCAAAATGTA A 1281
Domain Profile
S: 1     lklleligkGrygeVwkaklrgeevAvKifstedeaswkrEkeiyqtvllrhenilqfia  60
         + l+e igkGr+geVw++k+rgeevAvKifs+++e+sw+rE+eiyqtv+lrhenil+fia
Q: 128   IVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIA  187
         57899*******************************************************
S: 61    adkkeedsltelllvteyhekgsLsdyLkretldveellrlalslasGlahLHeeivgtk  120
         ad+k+++++t+l+lv++yhe+gsL+dyL+r+t++ve +++lals+asGlahLH+eivgt+
Q: 188   ADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQ  247
         ************************************************************
S: 121   gkkKpaiaHRDlkskNilvkkdltcciaDlGLalkleeekeeldlaansqvGtkRYmaPE  180
         g  KpaiaHRDlkskNilvkk++tcciaDlGLa++++++++++d+a n++vGtkRYmaPE
Q: 248   G--KPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPE  305
         *..*********************************************************
S: 181   vleealnlkdfeafkraDvYslgLvlWEvasRceevdeeveeyklpfeevvgsdPsleem  240
         vl++++n+k+fe+fkraD+Y++gLv+WE+a+Rc+  ++++e+y+lp+++ v+sdPs+eem
Q: 306   VLDDSINMKHFESFKRADIYAMGLVFWEIARRCSI-GGIHEDYQLPYYDLVPSDPSVEEM  364
         ***********************************.************************
S: 241   kevvvekklrPkipeawkkkealkelsklleecWdadpeaRltalrvkkrl  291
         ++vv+e+klrP+ip++w+++eal++++k+++ecW+a+++aRltalr+kk+l
Q: 365   RKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTL  415
         *************************************************97
Domain Sequence
(FASTA)
IVLQESIGKG RFGEVWRGKW RGEEVAVKIF SSREERSWFR EAEIYQTVML RHENILGFIA 60
ADNKDNGTWT QLWLVSDYHE HGSLFDYLNR YTVTVEGMIK LALSTASGLA HLHMEIVGTQ 120
GKPAIAHRDL KSKNILVKKN GTCCIADLGL AVRHDSATDT IDIAPNHRVG TKRYMAPEVL 180
DDSINMKHFE SFKRADIYAM GLVFWEIARR CSIGGIHEDY QLPYYDLVPS DPSVEEMRKV 240
VCEQKLRPNI PNRWQSCEAL RVMAKIMREC WYANGAARLT ALRIKKTL 288
Keyword3D-structure; Alternative splicing; Aortic aneurysm; Apoptosis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Craniosynostosis; Differentiation; Direct protein sequencing; Disease mutation; Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Serine/threonine-protein kinase; Signal; Tight junction; Transferase; Transmembrane; Transmembrane helix; Ubl conjugation.
Sequence SourceEnsembl
Orthology
Ortholog group
Danio rerio"; ?>Gadus morhua"; ?>Macaca mulatta"; ?>Mus musculus"; ?>Oreochromis niloticus"; ?>Oryzias latipes"; ?>Takifugu rubripes"; ?>
EKS-DAR-00613
EKS-GAM-00172
EKS-MAM-00277
EKS-MUM-00306
EKS-ORN-00353
EKS-ORL-00330
EKS-TAR-00355
Gene Ontology
GO:0016324; C:apical plasma membrane
GO:0016323; C:basolateral plasma membrane
GO:0005923; C:tight junction
GO:0070022; C:transforming growth factor beta receptor homodimeric complex
GO:0005524; F:ATP binding
GO:0046872; F:metal ion binding
GO:0046332; F:SMAD binding
GO:0050431; F:transforming growth factor beta binding
GO:0005025; F:transforming growth factor beta receptor activity, type I
GO:0005114; F:type II transforming growth factor beta receptor binding
GO:0000186; P:activation of MAPKK activity
GO:0007568; P:aging
GO:0001525; P:angiogenesis
GO:0009952; P:anterior/posterior pattern specification
GO:0006915; P:apoptotic process
GO:0048844; P:artery morphogenesis
GO:0001824; P:blastocyst development
GO:0007050; P:cell cycle arrest
GO:0071560; P:cellular response to transforming growth factor beta stimulus
GO:0030199; P:collagen fibril organization
GO:0048565; P:digestive tract development
GO:0007566; P:embryo implantation
GO:0048701; P:embryonic cranial skeleton morphogenesis
GO:0043542; P:endothelial cell migration
GO:0001837; P:epithelial to mesenchymal transition
GO:0008354; P:germ cell migration
GO:0007507; P:heart development
GO:0001701; P:in utero embryonic development
GO:0006917; P:induction of apoptosis
GO:0001822; P:kidney development
GO:0002088; P:lens development in camera-type eye
GO:0030324; P:lung development
GO:0043066; P:negative regulation of apoptotic process
GO:0032331; P:negative regulation of chondrocyte differentiation
GO:0045602; P:negative regulation of endothelial cell differentiation
GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway
GO:0048663; P:neuron fate commitment
GO:0031100; P:organ regeneration
GO:0060021; P:palate development
GO:0060017; P:parathyroid gland development
GO:0060389; P:pathway-restricted SMAD protein phosphorylation
GO:0018105; P:peptidyl-serine phosphorylation
GO:0018107; P:peptidyl-threonine phosphorylation
GO:0060037; P:pharyngeal system development
GO:0030307; P:positive regulation of cell growth
GO:0008284; P:positive regulation of cell proliferation
GO:0051272; P:positive regulation of cellular component movement
GO:0051491; P:positive regulation of filopodium assembly
GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0051897; P:positive regulation of protein kinase B signaling cascade
GO:0060391; P:positive regulation of SMAD protein import into nucleus
GO:0045893; P:positive regulation of transcription, DNA-dependent
GO:0009791; P:post-embryonic development
GO:0046777; P:protein autophosphorylation
GO:0043393; P:regulation of protein binding
GO:0031396; P:regulation of protein ubiquitination
GO:0070723; P:response to cholesterol
GO:0051602; P:response to electrical stimulus
GO:0043627; P:response to estrogen stimulus
GO:0001666; P:response to hypoxia
GO:0034695; P:response to prostaglandin E stimulus
GO:0009636; P:response to toxin
GO:0048538; P:thymus development
GO:0007179; P:transforming growth factor beta receptor signaling pathway
GO:0042060; P:wound healing
KEGG
hsa:7046;
InterPros
IPR000472; Activin_rcpt.
IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR008271; Ser/Thr_kinase_AS.
IPR003605; TGF_beta_rcpt_GS.
Pfam
PF01064; Activin_recp; 1.
PF00069; Pkinase; 1.
PF08515; TGF_beta_GS; 1.
SMARTs
SM00467; GS; 1.
Prosites
PS51256; GS; 1.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
Prints
Created Date20-Feb-2013