TGFR1_PIG
ID TGFR1_PIG Reviewed; 503 AA.
AC Q5CD18; Q5CD19;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS SER-8 AND
RP VAL-417.
RC TISSUE=Testis;
RX PubMed=16341765; DOI=10.1007/s10528-005-8165-0;
RA Shimanuki S., Mikawa A., Miyake Y., Hamasima N., Mikawa S., Awata T.;
RT "Structure and polymorphism analysis of transforming growth factor beta
RT receptor 1 (TGFBR1) in pigs.";
RL Biochem. Genet. 43:491-500(2005).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5CD18-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5CD18-2; Sequence=VSP_021594;
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 -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing donor splice
CC site. {ECO:0000305}.
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; AB182259; BAD91022.1; -; mRNA.
DR EMBL; AB182260; BAD91023.1; -; mRNA.
DR RefSeq; NP_001033728.1; NM_001038639.1. [Q5CD18-1]
DR AlphaFoldDB; Q5CD18; -.
DR BMRB; Q5CD18; -.
DR SMR; Q5CD18; -.
DR STRING; 9823.ENSSSCP00000029422; -.
DR PaxDb; Q5CD18; -.
DR GeneID; 396665; -.
DR KEGG; ssc:396665; -.
DR CTD; 7046; -.
DR eggNOG; KOG2052; Eukaryota.
DR InParanoid; Q5CD18; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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: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: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:0032924; P:activin receptor signaling pathway; ISS:AgBase.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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:0042118; P:endothelial cell activation; ISS:AgBase.
DR GO; GO:0007507; P:heart development; ISS:AgBase.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:AgBase.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:AgBase.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:AgBase.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:AgBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
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:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:AgBase.
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 Alternative splicing; Apoptosis; ATP-binding; Cell junction; Cell membrane;
KW Differentiation; Disulfide bond; Glycoprotein; Growth regulation;
KW Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; 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..503
FT /note="TGF-beta receptor type-1"
FT /id="PRO_0000260305"
FT TOPO_DOM 30..126
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 148..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 175..204
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 205..495
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 193..194
FT /note="FKBP1A-binding"
FT ACT_SITE 333
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 211..219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 185
FT /note="Phosphothreonine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 186
FT /note="Phosphothreonine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 187
FT /note="Phosphoserine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 189
FT /note="Phosphoserine; by TGFBR2"
FT /evidence="ECO:0000250|UniProtKB:P36897"
FT MOD_RES 191
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 391
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 111..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16341765"
FT /id="VSP_021594"
FT VARIANT 8
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:16341765"
FT VARIANT 417
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:16341765"
SQ SEQUENCE 503 AA; 56174 MW; CFA1EEC793401A4A CRC64;
MEVAAGAPRS RLLLFVLAAT ATLAPEATAF QCFCHLCTKD NFTCVTDGLC FVSVTETTDK
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS VTTTYCCNQD HCNKIELPTV GPFPGKPPSG
LGPVELAAVI AGPVCFVCIS LMLMVYICHN RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL
IYDMTTSGSG SGLPLLVQRT IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER
SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE
GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA DLGLAVRHDS
ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD IYAMGLVFWE IARRCSIGGI
HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL RPNIPNRWQS CEALRVMAKI MRECWYANGA
ARLTALRIKK TLSQLSQQEG IKM
