TGFR1_BOVIN
ID TGFR1_BOVIN Reviewed; 499 AA.
AC O46680;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=TGF-beta receptor type-1;
DE Short=TGFR-1;
DE EC=2.7.11.30;
DE AltName: Full=TGF-beta type I receptor;
DE AltName: Full=Transforming growth factor-beta receptor type I;
DE Short=TGF-beta receptor type I;
DE Short=TbetaR-I;
DE Flags: Precursor;
GN Name=TGFBR1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=9406190;
RX DOI=10.1002/(sici)1098-2795(199801)49:1<1::aid-mrd1>3.0.co;2-u;
RA Roelen B.A.J., Van Eijk M.J.T., Van Rooijen M.A., Bevers M.M., Larson J.H.,
RA Lewin H.A., Mummery C.L.;
RT "Molecular cloning, genetic mapping, and developmental expression of a
RT bovine transforming growth factor beta (TGF-beta) type I receptor.";
RL Mol. Reprod. Dev. 49:1-9(1998).
CC -!- FUNCTION: Transmembrane serine/threonine kinase forming with the TGF-
CC beta type II serine/threonine kinase receptor, TGFBR2, the non-
CC promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
CC Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to
CC the cytoplasm and is thus regulating a plethora of physiological and
CC pathological processes including cell cycle arrest in epithelial and
CC hematopoietic cells, control of mesenchymal cell proliferation and
CC differentiation, wound healing, extracellular matrix production,
CC immunosuppression and carcinogenesis. The formation of the receptor
CC complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound
CC to the cytokine dimer results in the phosphorylation and the activation
CC of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1
CC phosphorylates SMAD2 which dissociates from the receptor and interacts
CC with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the
CC nucleus where it modulates the transcription of the TGF-beta-regulated
CC genes. This constitutes the canonical SMAD-dependent TGF-beta signaling
CC cascade. Also involved in non-canonical, SMAD-independent TGF-beta
CC signaling pathways. For instance, TGFBR1 induces TRAF6
CC autoubiquitination which in turn results in MAP3K7 ubiquitination and
CC activation to trigger apoptosis. Also regulates epithelial to
CC mesenchymal transition through a SMAD-independent signaling pathway
CC through PARD6A phosphorylation and activation (By similarity).
CC {ECO:0000250|UniProtKB:P36897}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Kept in an inactive conformation by FKBP1A
CC preventing receptor activation in absence of ligand. CD109 is another
CC inhibitor of the receptor (By similarity).
CC {ECO:0000250|UniProtKB:P36897}.
CC -!- SUBUNIT: Homodimer; in the endoplasmic reticulum but also at the cell
CC membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands
CC assemble a functional receptor composed of two TGFBR1 and TGFBR2
CC heterodimers to form a ligand-receptor heterohexamer. The respective
CC affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics
CC of assembly of the receptor and may explain the different biological
CC activities of TGFB1, TGFB2 and TGFB3. Interacts with CD109; inhibits
CC TGF-beta receptor activation in keratinocytes. Interacts with RBPMS.
CC Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1
CC phosphorylation by TGFBR2 and stabilizes it in the inactive
CC conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits
CC SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and
CC MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A;
CC involved in TGF-beta induced epithelial to mesenchymal transition.
CC Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L,
CC SMURF1 and SMURF2 to the TGF-beta receptor (By similarity). Interacts
CC with USP15 and VPS39. Interacts with SDCBP (via C-terminus). Interacts
CC with CAV1 and this interaction is impaired in the presence of SDCBP (By
CC similarity). Interacts with APPL1; interaction is TGF beta dependent;
CC mediates trafficking of the TGFBR1 from the endosomes to the nucleus
CC via microtubules in a TRAF6-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P36897}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P36897};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P36897}.
CC Cell junction, tight junction {ECO:0000250|UniProtKB:P36897}. Membrane
CC raft {ECO:0000250|UniProtKB:P36897}. Cell surface
CC {ECO:0000250|UniProtKB:P36897}.
CC -!- PTM: Phosphorylated at basal levels in the absence of ligand. Activated
CC upon phosphorylation by TGFBR2, mainly in the GS domain.
CC Phosphorylation in the GS domain abrogates FKBP1A-binding (By
CC similarity). {ECO:0000250|UniProtKB:P36897}.
CC -!- PTM: N-Glycosylated. {ECO:0000250|UniProtKB:P36897}.
CC -!- PTM: Ubiquitinated; undergoes ubiquitination catalyzed by several E3
CC ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the
CC proteasomal and/or lysosomal degradation of the receptor thereby
CC negatively regulating its activity. Deubiquitinated by USP15, leading
CC to stabilization of the protein and enhanced TGF-beta signal. Its
CC ubiquitination and proteasome-mediated degradation is negatively
CC regulated by SDCBP (By similarity). {ECO:0000250|UniProtKB:P36897}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; U97485; AAC02717.1; -; mRNA.
DR RefSeq; NP_777046.1; NM_174621.2.
DR AlphaFoldDB; O46680; -.
DR SMR; O46680; -.
DR STRING; 9913.ENSBTAP00000024010; -.
DR PaxDb; O46680; -.
DR PRIDE; O46680; -.
DR Ensembl; ENSBTAT00000024010; ENSBTAP00000024010; ENSBTAG00000018035.
DR GeneID; 282382; -.
DR KEGG; bta:282382; -.
DR CTD; 7046; -.
DR VEuPathDB; HostDB:ENSBTAG00000018035; -.
DR VGNC; VGNC:35804; TGFBR1.
DR eggNOG; KOG2052; Eukaryota.
DR GeneTree; ENSGT00940000156394; -.
DR HOGENOM; CLU_000288_8_1_1; -.
DR InParanoid; O46680; -.
DR OMA; EMINMNH; -.
DR OrthoDB; 776697at2759; -.
DR TreeFam; TF314724; -.
DR Proteomes; UP000009136; Chromosome 8.
DR Bgee; ENSBTAG00000018035; Expressed in monocyte and 106 other tissues.
DR ExpressionAtlas; O46680; baseline and differential.
DR GO; GO:0048179; C:activin receptor complex; IBA:GO_Central.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:AgBase.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; IEA:Ensembl.
DR GO; GO:0048185; F:activin binding; IBA:GO_Central.
DR GO; GO:0016361; F:activin receptor activity, type I; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0070411; F:I-SMAD binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0046332; F:SMAD binding; IBA:GO_Central.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISS:AgBase.
DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; ISS:AgBase.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IEA:Ensembl.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISS:AgBase.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:AgBase.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0060982; P:coronary artery morphogenesis; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0042118; P:endothelial cell activation; ISS:AgBase.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:1905223; P:epicardium morphogenesis; IEA:Ensembl.
DR GO; GO:0046847; P:filopodium assembly; IEA:Ensembl.
DR GO; GO:0008354; P:germ cell migration; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; ISS:AgBase.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:AgBase.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:AgBase.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
DR GO; GO:0060017; P:parathyroid gland development; IEA:Ensembl.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:AgBase.
DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; IEA:Ensembl.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:1905075; P:positive regulation of tight junction disassembly; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:AgBase.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISS:AgBase.
DR GO; GO:0010468; P:regulation of gene expression; ISS:AgBase.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0070723; P:response to cholesterol; IEA:Ensembl.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:AgBase.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; IEA:Ensembl.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IEA:Ensembl.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IEA:Ensembl.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR000472; Activin_recp.
DR InterPro; IPR003605; GS_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08515; TGF_beta_GS; 1.
DR SMART; SM00467; GS; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS51256; GS; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell junction; Cell membrane; Differentiation;
KW Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Tight junction; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..29
FT /evidence="ECO:0000250"
FT CHAIN 30..499
FT /note="TGF-beta receptor type-1"
FT /id="PRO_0000254657"
FT TOPO_DOM 30..122
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 171..200
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 201..491
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 189..190
FT /note="FKBP1A-binding"
FT ACT_SITE 329
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 207..215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 181
FT /note="Phosphothreonine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 182
FT /note="Phosphothreonine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 183
FT /note="Phosphoserine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 185
FT /note="Phosphoserine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 187
FT /note="Phosphoserine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..50
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT DISULFID 34..37
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT DISULFID 44..67
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT DISULFID 82..96
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT DISULFID 97..102
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT CROSSLNK 387
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 499 AA; 55814 MW; 7FA311693CA938CD CRC64;
MEAAAATPRP RLFLLMLAAA ATLVPEATPL QCFCHLCTKD NFTCVTDGLC FVSVTETTDK
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS ITTTYCCNQD HCNKIELPTV GKPSSGLGPV
ELAAVIAGPV CFVCISLMLM VYICHNRTVI HHRVPNEEDP SLDRPFISEG TTLKDLIYDM
TTSGSGSGLP LLVQRTIART IVLQESIGKG RFGEVWRGKW RGEEVAVKIF SSREERSWFR
EAEIYQTVML RHENILGFIA ADNKDNGTWT QLWLVSDYHE HGSLFDYLNR YTVTVEGMIK
LALSTASGLA HLHMEIVGTQ GKPAIAHRDL KSKNILVKKN GTCCIADLGL AVRHDSATDT
IDIAPNHRVG TKRYMAPEVL DDSINMKHFE SFKRADIYAM GLVFWEVARR CSIGGIHEDY
QLPYYDLVPS DPSVEEMRKV VCEQKLRPNI PNRWQSCEAL RVMAKIMREC WYANGAARLT
ALRIKKTLSQ LSQQEGIKM
