InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Tgfbr1

Summary

InnateDB Protein

IDBP-146052.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Tgfbr1

Protein Name

transforming growth factor, beta receptor I

Synonyms

Alk-5; ALK5; AU017191; TbetaR-I; TbetaRI;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000007757

InnateDB Gene

IDBG-146050 (Tgfbr1)

Protein Structure

UniProt Annotation

Function

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). {ECO:0000250}.

Subcellular Localization

Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Cell junction, tight junction {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 37 experimentally validated interaction(s) in this database.
They are also associated with 69 interaction(s) predicted by orthology.

Experimentally validated
Total	37 [view]
Protein-Protein	36 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	69 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004675	transmembrane receptor protein serine/threonine kinase activity
GO:0004702	receptor signaling protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005024	transforming growth factor beta-activated receptor activity
GO:0005025	transforming growth factor beta receptor activity, type I
GO:0005114	type II transforming growth factor beta receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019838	growth factor binding
GO:0046332	SMAD binding
GO:0046872	metal ion binding
GO:0050431	transforming growth factor beta binding
GO:0070411	I-SMAD binding

Biological Process

GO:0000186	activation of MAPKK activity
GO:0001501	skeletal system development
GO:0001525	angiogenesis
GO:0001701	in utero embryonic development
GO:0001822	kidney development
GO:0001824	blastocyst development
GO:0001837	epithelial to mesenchymal transition
GO:0001937	negative regulation of endothelial cell proliferation
GO:0002088	lens development in camera-type eye
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007507	heart development
GO:0008284	positive regulation of cell proliferation
GO:0008354	germ cell migration
GO:0009791	post-embryonic development
GO:0009952	anterior/posterior pattern specification
GO:0010468	regulation of gene expression
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0023014	signal transduction by phosphorylation
GO:0030199	collagen fibril organization
GO:0030307	positive regulation of cell growth
GO:0031396	regulation of protein ubiquitination
GO:0032331	negative regulation of chondrocyte differentiation
GO:0043066	negative regulation of apoptotic process
GO:0043393	regulation of protein binding
GO:0043542	endothelial cell migration
GO:0045893	positive regulation of transcription, DNA-templated
GO:0048538	thymus development
GO:0048663	neuron fate commitment
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0048705	skeletal system morphogenesis
GO:0048844	artery morphogenesis
GO:0048870	cell motility
GO:0051272	positive regulation of cellular component movement
GO:0051491	positive regulation of filopodium assembly
GO:0051897	positive regulation of protein kinase B signaling
GO:0060017	parathyroid gland development
GO:0060021	palate development
GO:0060037	pharyngeal system development
GO:0060389	pathway-restricted SMAD protein phosphorylation
GO:0060391	positive regulation of SMAD protein import into nucleus
GO:0070723	response to cholesterol
GO:0071560	cellular response to transforming growth factor beta stimulus
GO:2001235	positive regulation of apoptotic signaling pathway
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0005768	endosome
GO:0005886	plasma membrane
GO:0005901	caveola
GO:0005923	tight junction
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex
GO:0045121	membrane raft

Protein Structure and Domains

PDB ID

MGI:98728

InterPro

IPR000472 TGF-beta receptor/activin receptor, type I/II
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR003605 TGF beta receptor, GS motif
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF01064
PF00069
PF07714
PF08515

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00467
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt