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TGF-beta receptor type-1; transforming growth factor-beta receptor type I; TGF-beta receptor type I; TGF-beta type I receptor; TbetaR-I; TGFR-1; serine/threonine protein kinase receptor R4; SKR4; activin receptor-like kinase 5; ALK-5 (TGFBR1)
Function:
- receptor for TGF-beta
- TGF-beta receptor-1 & TGF-beta receptor-2 form heteromeric complex after binding of TGF-beta
- on ligand binding, forms a receptor complex consisting of two type 2 & two type 1 transmembrane Ser/Thr kinases
- the type 2 receptors phosphorylate & activate type 1 receptors which autophosphorylate, then bind & activate SMAD transcriptional regulators
- interacts with CD109
- the unphosphorylated protein interacts with FKBP1A
- phosphorylation of the GS region abrogates FKBP1A binding
- interacts with SMAD2 when phosphorylated on several residues in the GS region
- phosphorylated at basal levels in the absence of ligand binding
- activated by multiple phosphorylation, mainly in the GS region
Cofactor: Mg+2 or Mn+2 (putative)
Structure:
- belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family, TGFB receptor subfamily
- contains 1 GS domain
- contains 1 protein kinase domain
Compartment: membrane
Expression:
- found in all tissues examined
- most abundant in placenta
- least abundant in brain & heart
Pathology:
- defects in TGFBR1 are the cause of syndromes associated with aortic aneurysm:
a) Loeys-Dietz syndrome type 1A
b) Loeys-Dietz syndrome type 2A
c) aortic aneurysm familial thoracic type 5
Interactions
molecular events
General
activin receptor like kinase (ALK)
protein subunit
serine/threonine kinase receptor
tgf beta receptor
Properties
SIZE: entity length = 503 aa
MW = 56 kD
COMPARTMENT: cellular membrane
STATE: active state
MOTIF: signal sequence {1-24}
cysteine residue {C36}
MODIFICATION: cysteine residue {C54}
cysteine residue {C38}
MODIFICATION: cysteine residue {C41}
cysteine residue {C41}
MODIFICATION: cysteine residue {C38}
N-glycosylation site {N45}
cysteine residue {C48}
MODIFICATION: cysteine residue {C71}
cysteine residue {C54}
MODIFICATION: cysteine residue {C36}
cysteine residue {C71}
MODIFICATION: cysteine residue {C48}
cysteine residue {C86}
MODIFICATION: cysteine residue {C100}
cysteine residue {C100}
MODIFICATION: cysteine residue {C86}
cysteine residue {C101}
MODIFICATION: cysteine residue {C106}
cysteine residue {C106}
MODIFICATION: cysteine residue {C101}
transmembrane domain {126-147}
GS {175-204}
MOTIF: Thr phosphorylation site {T185}
Thr phosphorylation site {T186}
Ser phosphorylation site {S187}
Ser phosphorylation site {S189}
Ser phosphorylation site {S191}
kinase domain
SITE: 205-495
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 211-219
ATP-binding site
NAME: ATP-binding site
SITE: 232-232
aspartate residue {D333}
Database Correlations
OMIM correlations
MORBIDMAP 190181
UniProt P36897
PFAM correlations
Entrez Gene 7046
Kegg hsa:7046
References
- UniProt :accession P36897
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TGFBR1
- Taga T & Kishimoto T
Cytokine receptors and signal transduction
FASEB J 6:3387 1992
PMID: 1334470
Component-of
transforming Growth Factor [TGF]-beta receptor complex