ACVR2A explained

Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene.^{[1] [2] [3]} ACVR2A is an activin type 2 receptor.

Function

This gene encodes activin A type II receptor. 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 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. Type II receptors are considered to be constitutively active kinases.^[3]

Interactions

ACVR2A has been shown to interact with:

• ACVR1B,^{[4] [5]}
• INHBA,^{[6] [7]} and
• SYNJ2BP.^{[8] [9]}

Further reading

• Welt CK . The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction . Curr. Opin. Obstet. Gynecol. . 14 . 3 . 317–23 . 2002 . 12032389 . 10.1097/00001703-200206000-00012 . 44327401 .
• Matzuk MM, Bradley A . Cloning of the human activin receptor cDNA reveals high evolutionary conservation . Biochim. Biophys. Acta . 1130 . 1 . 105–8 . 1992 . 1311955 . 10.1016/0167-4781(92)90472-C .
• Mathews LS, Vale WW . Expression cloning of an activin receptor, a predicted transmembrane serine kinase . Cell . 65 . 6 . 973–82 . 1991 . 1646080 . 10.1016/0092-8674(91)90549-E . 36407277 .
• Xu J, McKeehan K, Matsuzaki K, McKeehan WL . Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism . J. Biol. Chem. . 270 . 11 . 6308–13 . 1995 . 7890768 . 10.1074/jbc.270.11.6308 . free .
• Attisano L, Cárcamo J, Ventura F, Weis FM, Massagué J, Wrana JL . Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors . Cell . 75 . 4 . 671–80 . 1993 . 8242742 . 10.1016/0092-8674(93)90488-C . 25408172 .
• Peng C, Huang TH, Jeung EB, Donaldson CJ, Vale WW, Leung PC . Expression of the type II activin receptor gene in the human placenta . Endocrinology . 133 . 6 . 3046–9 . 1993 . 8243335 . 10.1210/endo.133.6.8243335 .
• De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ . 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 . 8612709 . 10.1006/excr.1996.0142 .
• Attisano L, Wrana JL, Montalvo E, Massagué J . Activation of signalling by the activin receptor complex . Mol. Cell. Biol. . 16 . 3 . 1066–73 . 1996 . 8622651 . 231089 . 10.1128/mcb.16.3.1066.
• Liu QY, Niranjan B, Gomes P, Gomm JJ, Davies D, Coombes RC, Buluwela L . Inhibitory effects of activin on the growth and morpholgenesis of primary and transformed mammary epithelial cells . Cancer Res. . 56 . 5 . 1155–63 . 1996 . 8640777 .
• Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K . Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5 . J. Biol. Chem. . 271 . 35 . 21345–52 . 1996 . 8702914 . 10.1074/jbc.271.35.21345 . free .
• Lebrun JJ, Vale WW . 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 . 9032295 . 231893 . 10.1128/mcb.17.3.1682.
• Macías-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL . Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2 . J. Biol. Chem. . 273 . 40 . 25628–36 . 1998 . 9748228 . 10.1074/jbc.273.40.25628 . free .
• Barbara NP, Wrana JL, Letarte M . Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily . J. Biol. Chem. . 274 . 2 . 584–94 . 1999 . 9872992 . 10.1074/jbc.274.2.584 . free .
• Lux A, Attisano L, Marchuk DA . Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1 . J. Biol. Chem. . 274 . 15 . 9984–92 . 1999 . 10187774 . 10.1074/jbc.274.15.9984 . free .
• D'Abronzo FH, Swearingen B, Klibanski A, Alexander JM . Mutational analysis of activin/transforming growth factor-beta type I and type II receptor kinases in human pituitary tumors . J. Clin. Endocrinol. Metab. . 84 . 5 . 1716–21 . 1999 . 10.1210/jcem.84.5.5704 . 10323406 .
• Ebisawa T, Tada K, Kitajima I, Tojo K, Sampath TK, Kawabata M, Miyazono K, Imamura T . Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation . J. Cell Sci. . 112 . 20 . 3519–27 . 1999 . 10.1242/jcs.112.20.3519 . 10504300 .
• van Schaik RH, Wierikx CD, Timmerman MA, Oomen MH, van Weerden WM, van der Kwast TH, van Steenbrugge GJ, de Jong FH . Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues . Br. J. Cancer . 82 . 1 . 112–7 . 2000 . 10638976 . 2363208 . 10.1054/bjoc.1999.0886 .
• Shoji H, Tsuchida K, Kishi H, Yamakawa N, Matsuzaki T, Liu Z, Nakamura T, Sugino H . Identification and characterization of a PDZ protein that interacts with activin type II receptors . J. Biol. Chem. . 275 . 8 . 5485–92 . 2000 . 10681527 . 10.1074/jbc.275.8.5485 . free .

Notes and References

1. Donaldson CJ, Mathews LS, Vale WW . Molecular cloning and binding properties of the human type II activin receptor . Biochem. Biophys. Res. Commun. . 184 . 1 . 310–6 . May 1992 . 1314589 . 10.1016/0006-291X(92)91194-U .
2. Bondestam J, Horelli-Kuitunen N, Hildén K, Ritvos O, Aaltonen J . Assignment of ACVR2 and ACVR2B the human activin receptor type II and IIB genes to chromosome bands 2q22.2-->q23.3 and 3p22 and the human follistatin gene (FST) to chromosome 5q11.2 by FISH . Cytogenet. Cell Genet. . 87 . 3–4 . 219–20 . April 2000 . 10702675 . 10.1159/000015429 . 36135054 .
3. Web site: Entrez Gene: ACVR2A activin A receptor, type IIA.
4. Lebrun JJ, Takabe K, Chen Y, Vale W . Roles of pathway-specific and inhibitory Smads in activin receptor signaling . Mol. Endocrinol. . 13 . 1 . 15–23 . January 1999 . 9892009 . 10.1210/mend.13.1.0218 . 26825706 . free .
5. De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ . 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 . May 1996 . 8612709 . 10.1006/excr.1996.0142 .
6. Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, Bilezikjian LM, Vale W . Betaglycan binds inhibin and can mediate functional antagonism of activin signalling . Nature . 404 . 6776 . 411–4 . March 2000 . 10746731 . 10.1038/35006129 . 2000Natur.404..411L . 4393629 .
7. Martens JW, de Winter JP, Timmerman MA, McLuskey A, van Schaik RH, Themmen AP, de Jong FH . Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells . Endocrinology . 138 . 7 . 2928–36 . July 1997 . 9202237 . 10.1210/endo.138.7.5250 . free .
8. Tsuchida K, Nakatani M, Matsuzaki T, Yamakawa N, Liu Z, Bao Y, Arai KY, Murakami T, Takehara Y, Kurisaki A, Sugino H . Novel factors in regulation of activin signaling . Mol. Cell. Endocrinol. . 225 . 1–2 . 1–8 . October 2004 . 15451561 . 10.1016/j.mce.2004.02.006 . 34666659 .
9. Matsuzaki T, Hanai S, Kishi H, Liu Z, Bao Y, Kikuchi A, Tsuchida K, Sugino H . Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway . J. Biol. Chem. . 277 . 21 . 19008–18 . May 2002 . 11882656 . 10.1074/jbc.M112472200 . free .