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Gene Review

ACVR2B  -  activin A receptor, type IIB

Homo sapiens

Synonyms: ACTR-IIB, ACTRIIB, ActR-IIB, Activin receptor type IIB, Activin receptor type-2B, ...
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Disease relevance of ACVR2B

  • No evidence of linkage at the ACVR2B locus has been detected in MODY families with unknown etiology for diabetes or found in affected sib pairs from families with type 2 diabetes [1].
  • Activin beta A subunit and activin receptor type IIB mRNA levels in both the chorion and amnion in women delivering at term or after preterm labor were significantly higher than in women delivering without undergoing labor (P < 0.01) [2].

High impact information on ACVR2B

  • We have solved the crystal structure of activin A bound to the extracellular domain of a type II receptor, ActRIIB, revealing the details of this interaction [3].
  • Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice [4].
  • Northern analysis showed that the 10- and 2.5-kb transcripts of hActR-IIB are more abundantly expressed than the 6.0- and 3.0-kb transcripts of hActR-II in K562 cells [5].
  • Activins, like other members of the transforming growth factor-beta (TGF-beta) superfamily, initiate signaling by assembling a complex of two types of transmembrane serine/threonine receptor kinases classified as type II (ActRII or ActRIIB) and type I (ALK4) [6].
  • Identification of a subset of biotinylated proteins among the different cell populations analyzed using matrix-assisted laser desorption ionization and tandem mass spectrometry uncovered proteins with a restricted expression pattern in some cell line(s), such as CD87 and the activin receptor type IIB [7].

Biological context of ACVR2B


Anatomical context of ACVR2B

  • Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test) [13].
  • The effect of activin is most likely mediated through specific receptors as mRNAs encoding several forms of activin receptors, namely ActR-I, ActR-IB, ActR-II and ActR-IIB are found in the preovulatory follicles as well as in cultured granulosa-luteal cells [14].
  • When COS-1 cells were transfected with type II receptor cDNAs, GDF-5 bound to ActR-II, ActR-IIB, and BMPR-II but not to transforming growth factor-beta type II receptor [15].
  • Syncytiotrophoblast and amnion cells hybridized to radiolabeled ActRIIB probe, whereas few cells within the structure of the villi and decidual cells hybridized to radiolabeled ActRII probe [16].
  • In situ hybridization on ovarian sections further localized ActRIIB mRNA to cytoplasm of oocytes at different stages of development [17].

Associations of ACVR2B with chemical compounds

  • Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins [18].

Physical interactions of ACVR2B

  • Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII [19].
  • Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own [20].

Regulatory relationships of ACVR2B

  • In our experiments, the first trimester placenta showed the highest levels of ActRIIB expression and human placenta from different stages expressed both type II and IIB activin receptor mRNAs [21].

Other interactions of ACVR2B

  • For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B) [1].
  • Genes currently implicated in human heterotaxy include ZIC3, LEFTYA, CRYPTIC, and ACVR2B [22].
  • There were no apparent differences in the distribution of the beta(A) subunit and receptors Alk2, ActRII and ActRIIB between control and preeclamptic tissues [23].

Analytical, diagnostic and therapeutic context of ACVR2B

  • The cDNA of the human activin receptor type IIB (hActR-IIB) was cloned and sequenced from two RNA sources, the K562 cells and the human fetal brain, which is, of the tissues screened by Northern blot analysis, the most abundant source of ActR-IIB RNA [5].
  • The evidence suggests that ActR-IIB acts as a primary activin receptor and ActR-IB acts as a downstream transducer of activin signals [20].
  • Molecular cloning has yielded genes encoding two type II receptors (ActRII and ActRIIB) and at least two type I receptors (ALK2 and ALK4) [24].
  • Real-time PCR quantification was used to measure mRNA levels of activin-betaA1 and -betaA2, as well as two type II receptors, ActRIIA and ActRIIB, in the zebrafish ovary [25].
  • Immunocytochemistry demonstrated clear staining for the betaA, betaB subunits and ActRIIA and ActRIIB that increased in intensity from the isthmus to the ampulla [26].


  1. No evidence for linkage or for diabetes-associated mutations in the activin type 2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the young or type 2 diabetes. Dupont, S., Hani, E.H., Cras-Méneur, C., De Matos, F., Lobbens, S., Lecoeur, C., Vaxillaire, M., Scharfmann, R., Froguel, P. Diabetes (2001) [Pubmed]
  2. High levels of fetal membrane activin beta A and activin receptor IIB mRNAs and augmented concentration of amniotic fluid activin A in women in term or preterm labor. Petraglia, F., Di Blasio, A.M., Florio, P., Gallo, R., Genazzani, A.R., Woodruff, T.K., Vale, W. J. Endocrinol. (1997) [Pubmed]
  3. Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions. Thompson, T.B., Woodruff, T.K., Jardetzky, T.S. EMBO J. (2003) [Pubmed]
  4. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Lee, S.J., Reed, L.A., Davies, M.V., Girgenrath, S., Goad, M.E., Tomkinson, K.N., Wright, J.F., Barker, C., Ehrmantraut, G., Holmstrom, J., Trowell, B., Gertz, B., Jiang, M.S., Sebald, S.M., Matzuk, M., Li, E., Liang, L.F., Quattlebaum, E., Stotish, R.L., Wolfman, N.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor. Hildén, K., Tuuri, T., Erämaa, M., Ritvos, O. Blood (1994) [Pubmed]
  6. Identification of a functional binding site for activin on the type I receptor ALK4. Harrison, C.A., Gray, P.C., Koerber, S.C., Fischer, W., Vale, W. J. Biol. Chem. (2003) [Pubmed]
  7. Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. Shin, B.K., Wang, H., Yim, A.M., Le Naour, F., Brichory, F., Jang, J.H., Zhao, R., Puravs, E., Tra, J., Michael, C.W., Misek, D.E., Hanash, S.M. J. Biol. Chem. (2003) [Pubmed]
  8. Expression of activin and inhibin subunits, receptors and binding proteins in Human adrenocortical neoplasms. Hofland, J., Timmerman, M.A., de Herder, W.W., van Schaik, R.H., de Krijger, R.R., de Jong, F.H. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  9. DNA mutation analysis in heterotaxy. Ware, S.M. Methods Mol. Med. (2006) [Pubmed]
  10. Ovarian activin receptor subtype and follistatin gene expression in rats: reciprocal regulation by gonadotropins. Aloi, J.A., Marshall, J.C., Yasin, M., Gilrain, J.T., Haisenleder, D.J., Dalkin, A.C. Biol. Reprod. (1997) [Pubmed]
  11. Genomic organization and mapping of the human activin receptor type IIB (hActR-IIB) gene. Ishikawa, S., Kai, M., Murata, Y., Tamari, M., Daigo, Y., Murano, T., Ogawa, M., Nakamura, Y. J. Hum. Genet. (1998) [Pubmed]
  12. BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens. Kusumegi, T., Tanaka, J., Kawano, M., Yonemoto, J., Tohyama, C., Sone, H. J. Biochem. Mol. Toxicol. (2004) [Pubmed]
  13. Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues. van Schaik, R.H., Wierikx, C.D., Timmerman, M.A., Oomen, M.H., van Weerden, W.M., van der Kwast, T.H., van Steenbrugge, G.J., de Jong, F.H. Br. J. Cancer (2000) [Pubmed]
  14. Activin and follistatin as local regulators in the human ovary. Peng, C., Ohno, T., Khorasheh, S., Leung, P.C. Biol. Signals (1996) [Pubmed]
  15. Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. Nishitoh, H., Ichijo, H., Kimura, M., Matsumoto, T., Makishima, F., Yamaguchi, A., Yamashita, H., Enomoto, S., Miyazono, K. J. Biol. Chem. (1996) [Pubmed]
  16. Activin at parturition: changes of maternal serum levels and evidence for binding sites in placenta and fetal membranes. Petraglia, F., Gallinelli, A., De Vita, D., Lewis, K., Mathews, L., Vale, W. Obstetrics and gynecology. (1994) [Pubmed]
  17. Cloning of zebrafish activin type IIB receptor (ActRIIB) cDNA and mRNA expression of ActRIIB in embryos and adult tissues. Garg, R.R., Bally-Cuif, L., Lee, S.E., Gong, Z., Ni, X., Hew, C.L., Peng, C. Mol. Cell. Endocrinol. (1999) [Pubmed]
  18. Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling. Liu, Z.H., Tsuchida, K., Matsuzaki, T., Bao, Y.L., Kurisaki, A., Sugino, H. J. Endocrinol. (2006) [Pubmed]
  19. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. Parks, W.T., Frank, D.B., Huff, C., Renfrew Haft, C., Martin, J., Meng, X., de Caestecker, M.P., McNally, J.G., Reddi, A., Taylor, S.I., Roberts, A.B., Wang, T., Lechleider, R.J. J. Biol. Chem. (2001) [Pubmed]
  20. Activation of signalling by the activin receptor complex. Attisano, L., Wrana, J.L., Montalvo, E., Massagué, J. Mol. Cell. Biol. (1996) [Pubmed]
  21. Type II and type IIB activin receptors in human placenta. Shinozaki, H., Minegishi, T., Nakamura, K., Tano, M., Miyamoto, K., Ibuki, Y. Life Sci. (1995) [Pubmed]
  22. Molecular genetics of heterotaxy syndromes. Belmont, J.W., Mohapatra, B., Towbin, J.A., Ware, S.M. Curr. Opin. Cardiol. (2004) [Pubmed]
  23. Activin A and activin receptors in gestational tissue from preeclamptic pregnancies. Manuelpillai, U., Schneider-Kolsky, M., Dole, A., Wallace, E.M. J. Endocrinol. (2001) [Pubmed]
  24. Activin receptors: cellular signalling by receptor serine kinases. Zimmerman, C.M., Mathews, L.S. Biochem. Soc. Symp. (1996) [Pubmed]
  25. Cloning of a second form of activin-betaA cDNA and regulation of activin-betaA subunits and activin type II receptor mRNA expression by gonadotropin in the zebrafish ovary. DiMuccio, T., Mukai, S.T., Clelland, E., Kohli, G., Cuartero, M., Wu, T., Peng, C. Gen. Comp. Endocrinol. (2005) [Pubmed]
  26. Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx. Refaat, B.A., Bahathiq, A.O., Sockanathan, S., Stewart, R.L., Wells, M., Ledger, W.L. Reproduction (2004) [Pubmed]
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