Q5CD18 (TGFR1_PIG) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 74. History...
Names and origin
|Protein names||Recommended name:|
TGF-beta receptor type-1
TGF-beta type I receptor
Transforming growth factor-beta receptor type I
Short name=TGF-beta receptor type I
|Organism||Sus scrofa (Pig) [Reference proteome]|
|Taxonomic identifier||9823 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus|
|Sequence length||503 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Transmembrane serine/threonine kinase forming with the TGF-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.
ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Magnesium or manganese By similarity.
Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor By similarity.
Homodimer; in the endoplasmic reticulum but also at the cell membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor By similarity. Interacts with USP15 and VPS39 By similarity.
Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding By similarity.
N-Glycosylated By similarity.
Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal By similarity.
Contains 1 GS domain.
Contains 1 protein kinase domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: Q5CD18-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: Q5CD18-2) |
The sequence of this isoform differs from the canonical sequence as follows:
|Note: May be due to a competing donnor splice site.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 29||29||By similarity|
|Chain||30 – 503||474||TGF-beta receptor type-1||PRO_0000260305|
|Topological domain||30 – 126||97||Extracellular Potential|
|Transmembrane||127 – 147||21||Helical; Potential|
|Topological domain||148 – 503||356||Cytoplasmic Potential|
|Domain||175 – 204||30||GS|
|Domain||205 – 495||291||Protein kinase|
|Nucleotide binding||211 – 219||9||ATP By similarity|
|Motif||193 – 194||2||FKBP1A-binding|
|Active site||333||1||Proton acceptor By similarity|
|Binding site||232||1||ATP By similarity|
Amino acid modifications
|Modified residue||165||1||Phosphoserine By similarity|
|Modified residue||185||1||Phosphothreonine; by TGFBR2 By similarity|
|Modified residue||186||1||Phosphothreonine; by TGFBR2 By similarity|
|Modified residue||187||1||Phosphoserine; by TGFBR2 By similarity|
|Modified residue||189||1||Phosphoserine; by TGFBR2 By similarity|
|Modified residue||191||1||Phosphoserine; by TGFBR2 By similarity|
|Glycosylation||41||1||N-linked (GlcNAc...) Potential|
|Cross-link||391||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Alternative sequence||111 – 114||4||Missing in isoform 2.||VSP_021594|
|Natural variant||8||1||P → S. Ref.1|
|Natural variant||417||1||I → V. Ref.1|
|||"Structure and polymorphism analysis of transforming growth factor beta receptor 1 (TGFBR1) in pigs."|
Shimanuki S., Mikawa A., Miyake Y., Hamasima N., Mikawa S., Awata T.
Biochem. Genet. 43:491-500(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS SER-8 AND VAL-417.
|AB182259 mRNA. Translation: BAD91022.1.|
AB182260 mRNA. Translation: BAD91023.1.
|RefSeq||NP_001033728.1. NM_001038639.1. |
3D structure databases
|SMR||Q5CD18. Positions 29-107, 171-500. |
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR000472. Activin_rcpt. |
|Pfam||PF01064. Activin_recp. 1 hit. |
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
|SMART||SM00467. GS. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS51256. GS. 1 hit. |
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q5CD18|
Secondary accession number(s): Q5CD19
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families