EKS-BOT-00275

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-BOT-00275

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/STKR	467.3	1.9E-140	201	488	288

Status

Reviewed

Ensembl Protein

ENSBTAP00000024010

UniProt Accession

O46680;

Protein Name

TGF-beta receptor type-1

Protein Synonyms/Alias

TGFR-1; TGF-beta type I receptor; Transforming growth factor-beta receptor type I; TGF-beta receptor type I; TbetaR-I;

Gene Name

TGFBR1

Gene Synonyms/Alias

TGFBR1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSBTAG00000018035	ENSBTAP00000024010	ENSBTAT00000024010

Organism

Bos taurus

Functional Description

Transmembrane 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 (By similarity).

Protein Length

499

Protein Sequence
(FASTA)

MEAAAATPRP RLFLLMLAAA ATLVPEATPL QCFCHLCTKD NFTCVTDGLC FVSVTETTDK 60

VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS ITTTYCCNQD HCNKIELPTV GKPSSGLGPV 120

ELAAVIAGPV CFVCISLMLM VYICHNRTVI HHRVPNEEDP SLDRPFISEG TTLKDLIYDM 180

TTSGSGSGLP LLVQRTIART IVLQESIGKG RFGEVWRGKW RGEEVAVKIF SSREERSWFR 240

EAEIYQTVML RHENILGFIA ADNKDNGTWT QLWLVSDYHE HGSLFDYLNR YTVTVEGMIK 300

LALSTASGLA HLHMEIVGTQ GKPAIAHRDL KSKNILVKKN GTCCIADLGL AVRHDSATDT 360

IDIAPNHRVG TKRYMAPEVL DDSINMKHFE SFKRADIYAM GLVFWEVARR CSIGGIHEDY 420

QLPYYDLVPS DPSVEEMRKV VCEQKLRPNI PNRWQSCEAL RVMAKIMREC WYANGAARLT 480

ALRIKKTLSQ LSQQEGIKM 499

Nucleotide Sequence
(FASTA)

ATGGAGGCAG CGGCCGCTAC TCCGCGTCCC CGGCTGTTCC TCCTCATGCT GGCGGCGGCG 60

GCCACGCTGG TCCCGGAGGC AACGCCATTA CAGTGTTTCT GCCACCTTTG TACAAAAGAC 120

AATTTTACTT GTGTCACAGA TGGGCTTTGC TTTGTCTCTG TCACAGAGAC CACAGACAAA 180

GTTATACATA ATAGCATGTG TATAGCTGAA ATTGACCTAA TTCCACGAGA CAGGCCATTT 240

GTATGTGCAC CATCTTCAAA AACTGGGTCT ATAACTACAA CATATTGCTG CAACCAGGAC 300

CACTGCAATA AAATAGAACT TCCAACTGTT GGAAAGCCAT CATCTGGCCT TGGTCCTGTT 360

GAACTGGCAG CTGTCATTGC TGGACCAGTC TGCTTTGTCT GTATCTCACT CATGTTGATG 420

GTCTATATTT GCCATAACCG CACTGTCATT CACCATCGAG TGCCAAATGA AGAGGATCCC 480

TCGTTAGATC GCCCTTTTAT TTCAGAGGGT ACAACGTTAA AAGATTTAAT TTACGACATG 540

ACAACATCAG GTTCTGGATC AGGTTTACCA TTGCTTGTTC AGAGAACAAT TGCGAGAACT 600

ATTGTGTTAC AAGAAAGTAT TGGCAAAGGT CGTTTTGGAG AAGTTTGGCG AGGAAAATGG 660

AGAGGAGAAG AAGTTGCTGT TAAAATATTC TCCTCTAGAG AAGAACGTTC ATGGTTCCGT 720

GAAGCAGAGA TTTATCAGAC TGTCATGTTA CGTCACGAAA ACATCTTGGG ATTTATAGCA 780

GCAGACAATA AAGACAATGG CACATGGACT CAGCTCTGGT TGGTGTCAGA TTATCATGAG 840

CACGGATCCC TTTTTGATTA TTTGAACAGA TACACAGTTA CTGTGGAAGG AATGATAAAA 900

CTTGCTCTGT CCACAGCAAG TGGACTTGCC CATCTTCACA TGGAGATAGT TGGTACCCAA 960

GGAAAACCAG CCATAGCTCA TAGGGATTTG AAATCAAAGA ATATCTTGGT AAAGAAGAAT 1020

GGAACTTGCT GTATTGCAGA CTTAGGATTG GCAGTAAGGC ATGATTCGGC CACGGATACA 1080

ATTGACATTG CTCCAAACCA CAGAGTGGGA ACAAAAAGGT ACATGGCCCC TGAAGTTCTA 1140

GATGATTCCA TAAATATGAA ACACTTTGAA TCCTTCAAAC GTGCTGACAT CTATGCAATG 1200

GGACTAGTAT TCTGGGAAGT AGCTCGACGA TGTTCCATTG GTGGAATACA TGAAGATTAC 1260

CAGCTGCCTT ATTATGATCT TGTACCTTCC GATCCATCAG TTGAAGAAAT GAGAAAAGTT 1320

GTTTGTGAAC AGAAGTTAAG GCCAAATATT CCAAACAGAT GGCAGAGCTG TGAAGCCTTG 1380

AGAGTAATGG CTAAAATTAT GAGAGAATGT TGGTATGCCA ATGGAGCAGC TAGGCTTACA 1440

GCTTTGCGGA TTAAGAAAAC ATTGTCACAA CTCAGTCAGC AGGAAGGCAT CAAAATGTAA 1500

Domain Profile

S: 1     lklleligkGrygeVwkaklrgeevAvKifstedeaswkrEkeiyqtvllrhenilqfia  60

         + l+e igkGr+geVw++k+rgeevAvKifs+++e+sw+rE+eiyqtv+lrhenil+fia

Q: 201   IVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIA  260

         57899*******************************************************

S: 61    adkkeedsltelllvteyhekgsLsdyLkretldveellrlalslasGlahLHeeivgtk  120

         ad+k+++++t+l+lv++yhe+gsL+dyL+r+t++ve +++lals+asGlahLH+eivgt+

Q: 261   ADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQ  320

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

S: 121   gkkKpaiaHRDlkskNilvkkdltcciaDlGLalkleeekeeldlaansqvGtkRYmaPE  180

         g  KpaiaHRDlkskNilvkk++tcciaDlGLa++++++++++d+a n++vGtkRYmaPE

Q: 321   G--KPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPE  378

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

S: 181   vleealnlkdfeafkraDvYslgLvlWEvasRceevdeeveeyklpfeevvgsdPsleem  240

         vl++++n+k+fe+fkraD+Y++gLv+WEva+Rc+  ++++e+y+lp+++ v+sdPs+eem

Q: 379   VLDDSINMKHFESFKRADIYAMGLVFWEVARRCSI-GGIHEDYQLPYYDLVPSDPSVEEM  437

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

S: 241   kevvvekklrPkipeawkkkealkelsklleecWdadpeaRltalrvkkrl  291

         ++vv+e+klrP+ip++w+++eal++++k+++ecW+a+++aRltalr+kk+l

Q: 438   RKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTL  488

         *************************************************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 GLVFWEVARR CSIGGIHEDY QLPYYDLVPS DPSVEEMRKV 240

VCEQKLRPNI PNRWQSCEAL RVMAKIMREC WYANGAARLT ALRIKKTL 288

Keyword

Apoptosis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Differentiation; Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Serine/threonine-protein kinase; Signal; Tight junction; Transferase; Transmembrane; Transmembrane helix; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>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"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sorex araneus"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Tupaia belangeri"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0016021	; C:integral to membrane
GO:0044459	; C:plasma membrane part
GO:0043235	; C:receptor complex
GO:0005923	; C:tight junction
GO:0005524	; F:ATP binding
GO:0046872	; F:metal ion binding
GO:0005025	; F:transforming growth factor beta receptor activity, type I
GO:0000186	; P:activation of MAPKK activity
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:0071560	; P:cellular response to transforming growth factor beta stimulus
GO:0030199	; P:collagen fibril organization
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:0006917	; P:induction of apoptosis
GO:0001822	; P:kidney development
GO:0002088	; P:lens development in camera-type eye
GO:0043066	; P:negative regulation of apoptotic process
GO:0032331	; P:negative regulation of chondrocyte differentiation
GO:0048663	; P:neuron fate commitment
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:0043393	; P:regulation of protein binding
GO:0031396	; P:regulation of protein ubiquitination
GO:0048538	; P:thymus development
GO:0007179	; P:transforming growth factor beta receptor signaling pathway

KEGG

bta:282382

;

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 Date

20-Feb-2013