InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ACVR2B

Summary

InnateDB Protein

IDBP-25936.6

Last Modified

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

Gene Symbol

ACVR2B

Protein Name

activin A receptor, type IIB

Synonyms

ActR-IIB; ACTRIIB; HTX4;

Species

Homo sapiens

Ensembl Protein

ENSP00000340361

InnateDB Gene

IDBG-25934 (ACVR2B)

Protein Structure

UniProt Annotation

Function

Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. {ECO:0000269PubMed:8622651}.

Subcellular Localization

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

Disease Associations

Heterotaxy, visceral, 4, autosomal (HTX4) [MIM:613751]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. HTX4 clinical features include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver. {ECO:0000269PubMed:9916847}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 30 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	30 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [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:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005024	transforming growth factor beta-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016362	activin receptor activity, type II
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019838	growth factor binding
GO:0034711	inhibin binding
GO:0046872	metal ion binding
GO:0048185	activin binding

Biological Process

GO:0001501	skeletal system development
GO:0001702	gastrulation with mouth forming second
GO:0001822	kidney development
GO:0001946	lymphangiogenesis
GO:0001974	blood vessel remodeling
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007178	transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007368	determination of left/right symmetry
GO:0007389	pattern specification process
GO:0007498	mesoderm development
GO:0007507	heart development
GO:0009749	response to glucose
GO:0009791	post-embryonic development
GO:0009952	anterior/posterior pattern specification
GO:0009966	regulation of signal transduction
GO:0023014	signal transduction by phosphorylation
GO:0030073	insulin secretion
GO:0030324	lung development
GO:0030501	positive regulation of bone mineralization
GO:0030509	BMP signaling pathway
GO:0031016	pancreas development
GO:0032147	activation of protein kinase activity
GO:0032924	activin receptor signaling pathway
GO:0032927	positive regulation of activin receptor signaling pathway
GO:0035265	organ growth
GO:0042475	odontogenesis of dentin-containing tooth
GO:0045669	positive regulation of osteoblast differentiation
GO:0048617	embryonic foregut morphogenesis
GO:0048705	skeletal system morphogenesis
GO:0060021	palate development
GO:0060836	lymphatic endothelial cell differentiation
GO:0060840	artery development
GO:0060841	venous blood vessel development
GO:0061298	retina vasculature development in camera-type eye

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000333 Ser/Thr protein kinase, TGFB receptor
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
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF01064
PF00069
PF07714

PRINTS

PR00653
PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt