InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TGFBR2

Summary

InnateDB Protein

IDBP-23363.5

Last Modified

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

Gene Symbol

TGFBR2

Protein Name

transforming growth factor, beta receptor II (70/80kDa)

Synonyms

AAT3; FAA3; LDS1B; LDS2; LDS2B; MFS2; RIIC; TAAD2; TGFbeta-RII; TGFR-2;

Species

Homo sapiens

Ensembl Protein

ENSP00000295754

InnateDB Gene

IDBG-23359 (TGFBR2)

Protein Structure

UniProt Annotation

Function

Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, 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 TGFRB1 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. {ECO:0000269PubMed:7774578}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:1310899}; Single-pass type I membrane protein {ECO:0000269PubMed:1310899}.

Disease Associations

Hereditary non-polyposis colorectal cancer 6 (HNPCC6) [MIM:614331]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269PubMed:9590282}. Note=The disease is caused by mutations affecting the gene represented in this entry.Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. {ECO:0000269PubMed:10789724}. Note=The disease is caused by mutations affecting the gene represented in this entry.Loeys-Dietz syndrome 2 (LDS2) [MIM:610168]: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. {ECO:0000269PubMed:15235604, ECO:0000269PubMed:15731757, ECO:0000269PubMed:16027248, ECO:0000269PubMed:16251899, ECO:0000269PubMed:19883511, ECO:0000269PubMed:20101701, ECO:0000269PubMed:20358619, ECO:0000269PubMed:21949523, ECO:0000269PubMed:22113417}. Note=The disease is caused by mutations affecting the gene represented in this entry. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2 by the OMIM resource. {ECO:0000269PubMed:16027248}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 98 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	98 [view]
Protein-Protein	84 [view]
Protein-DNA	12 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	12 [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:0004872	receptor activity
GO:0005024	transforming growth factor beta-activated receptor activity
GO:0005026	transforming growth factor beta receptor activity, type II
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0005539	glycosaminoglycan binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0034713	type I transforming growth factor beta receptor binding
GO:0034714	type III transforming growth factor beta receptor binding
GO:0046332	SMAD binding
GO:0046872	metal ion binding
GO:0050431	transforming growth factor beta binding

Biological Process

GO:0001568	blood vessel development
GO:0001569	patterning of blood vessels
GO:0001570	vasculogenesis
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0002651	positive regulation of tolerance induction to self antigen
GO:0002663	positive regulation of B cell tolerance induction
GO:0002666	positive regulation of T cell tolerance induction
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007420	brain development
GO:0007507	heart development
GO:0008284	positive regulation of cell proliferation
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0023014	signal transduction by phosphorylation
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0032147	activation of protein kinase activity
GO:0035162	embryonic hemopoiesis
GO:0042127	regulation of cell proliferation
GO:0042493	response to drug
GO:0043011	myeloid dendritic cell differentiation
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0051138	positive regulation of NK T cell differentiation
GO:0060021	palate development
GO:0060389	pathway-restricted SMAD protein phosphorylation
GO:0070723	response to cholesterol
GO:2000379	positive regulation of reactive oxygen species metabolic process

Cellular Component

GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005901	caveola
GO:0009897	external side of plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex
GO:0070022	transforming growth factor beta receptor homodimeric complex

Protein Structure and Domains

PDB ID

InterPro

IPR000333 Ser/Thr protein kinase, TGFB receptor
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR015013 Transforming growth factor beta receptor 2 ectodomain
IPR017194 Transforming growth factor-beta receptor, type II
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF08917

PRINTS

PR00653
PR00109

PIRSF

PIRSF037393

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References