Biology:ACVR1B

Short description: Protein-coding gene in humans

Generic protein structure example

Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.

ACVR1B or ALK-4 acts as a transducer of activin or activin-like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3. ACVR1B also transduces signals of nodal, GDF-1, and Vg1; however, unlike activin, they require other coreceptor molecules such as the protein Cripto.

Function

Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling, and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type IB receptor, composed of 11 exons. Alternative splicing and alternative polyadenylation result in 3 fully described transcript variants. The mRNA expression of variants 1, 2, and 3 is confirmed, and a potential fourth variant contains an alternative exon 8 and lacks exons 9 through 11, but its mRNA expression has not been confirmed.

Interactions

ACVR1B has been shown to interact with

• ACVR2A, and ACVR2B

External links

• Human ACVR1B genome location and ACVR1B gene details page in the UCSC Genome Browser.

Further reading

• "The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction". Curr. Opin. Obstet. Gynecol. 14 (3): 317–23. 2002. doi:10.1097/00001703-200206000-00012. PMID 12032389. 
• "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Mol. Cell. Biol. 15 (7): 3479–86. 1995. doi:10.1128/mcb.15.7.3479. PMID 7791754. 
• "Genomic structure and cloned cDNAs predict that four variants in the kinase domain of serine/threonine kinase receptors arise by alternative splicing and poly(A) addition". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 7957–61. 1994. doi:10.1073/pnas.91.17.7957. PMID 8058741. Bibcode: 1994PNAS...91.7957X. 
• "Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin". Mol. Cell. Biol. 14 (6): 3810–21. 1994. doi:10.1128/MCB.14.6.3810. PMID 8196624. 
• "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res. 224 (2): 323–34. 1996. doi:10.1006/excr.1996.0142. PMID 8612709. 
• "Activation of signalling by the activin receptor complex". Mol. Cell. Biol. 16 (3): 1066–73. 1996. doi:10.1128/MCB.16.3.1066. PMID 8622651. 
• "Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation". Mol. Cell. Biol. 17 (3): 1682–91. 1997. doi:10.1128/MCB.17.3.1682. PMID 9032295. 
• "Chromosomal localization of three human genes encoding members of the TGF-beta superfamily of type I serine/threonine kinase receptors". Mamm. Genome 9 (3): 266–8. 1998. doi:10.1007/s003359900745. PMID 9501322. 
• "Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors". J. Biol. Chem. 273 (39): 25364–70. 1998. doi:10.1074/jbc.273.39.25364. PMID 9738003. 
• "The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells". Cell. Signal. 10 (10): 743–9. 1998. doi:10.1016/S0898-6568(98)00021-7. PMID 9884026. 
• "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. 13 (1): 15–23. 1999. doi:10.1210/mend.13.1.0218. PMID 9892009. 
• "Identification of a binding site on the type II activin receptor for activin and inhibin". J. Biol. Chem. 275 (5): 3206–12. 2000. doi:10.1074/jbc.275.5.3206. PMID 10652306. 
• "Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling". Mol. Endocrinol. 14 (12): 2066–75. 2000. doi:10.1210/mend.14.12.0570. PMID 11117535. 
• "ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3254–7. 2001. doi:10.1073/pnas.051484398. PMID 11248065. Bibcode: 2001PNAS...98.3254S. 
• "Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP)". Mol. Endocrinol. 15 (4): 668–79. 2001. doi:10.1210/mend.15.4.0616. PMID 11266516. 
• "Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone". J. Biol. Chem. 276 (22): 19495–502. 2001. doi:10.1074/jbc.M006473200. PMID 11278302. 
• "Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases". J. Biol. Chem. 276 (22): 19332–9. 2001. doi:10.1074/jbc.M100606200. PMID 11279102. 
• "X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling". J. Biol. Chem. 276 (28): 26542–9. 2001. doi:10.1074/jbc.M100331200. PMID 11356828. 
• "Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells". Mol. Cell. Biol. 22 (8): 2586–97. 2002. doi:10.1128/MCB.22.8.2586-2597.2002. PMID 11909953.