InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ACVR1B

Summary

InnateDB Protein

IDBP-601570.3

Last Modified

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

Gene Symbol

ACVR1B

Protein Name

activin A receptor, type IB

Synonyms

ACTRIB; ACVRLK4; ALK4; SKR2;

Species

Homo sapiens

Ensembl Protein

ENSP00000442885

InnateDB Gene

IDBG-33695 (ACVR1B)

Protein Structure

UniProt Annotation

Function

Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a 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, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas 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 such as ACVR1B. 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. ACVR1B also phosphorylates TDP2. {ECO:0000269PubMed:12364468, ECO:0000269PubMed:12639945, ECO:0000269PubMed:18039968, ECO:0000269PubMed:20226172, ECO:0000269PubMed:8196624, ECO:0000269PubMed:9032295, ECO:0000269PubMed:9892009}.

Subcellular Localization

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

Disease Associations

Note=ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis.

Tissue Specificity

Expressed in many tissues, most strongly in kidney, pancreas, brain, lung, and liver.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 39 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	39 [view]
Protein-Protein	38 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	2 [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:0004713	protein tyrosine kinase activity
GO:0005024	transforming growth factor beta-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016361	activin receptor activity, type I
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017002	activin-activated receptor activity
GO:0019838	growth factor binding
GO:0031625	ubiquitin protein ligase binding
GO:0034711	inhibin binding
GO:0046332	SMAD binding
GO:0046872	metal ion binding
GO:0048185	activin binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
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:0018107	peptidyl-threonine phosphorylation
GO:0030308	negative regulation of cell growth
GO:0032924	activin receptor signaling pathway
GO:0032927	positive regulation of activin receptor signaling pathway
GO:0038092	nodal signaling pathway
GO:0045648	positive regulation of erythrocyte differentiation
GO:0046777	protein autophosphorylation
GO:0097191	extrinsic apoptotic signaling pathway
GO:1901165	positive regulation of trophoblast cell migration

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

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