ACVR2A

Activin A receptor, type IIA

PDB rendering based on 1bte.

Available structures
PDB	1bte, 1lx5, 2goo

Identifiers

Symbols

ACVR2A; ACTRII; ACVR2

External IDs

OMIM: 102581 MGI: 102806 HomoloGene: 20391 GeneCards: ACVR2A Gene

EC number

2.7.11.30

Gene Ontology
Molecular function	• nucleotide binding • transmembrane receptor protein serine/threonine kinase activity • receptor signaling protein serine/threonine kinase activity • transforming growth factor beta receptor activity • protein binding • protein binding • ATP binding • coreceptor activity • activin receptor activity, type II • activin receptor activity • growth factor binding • protein self-association • metal ion binding • activin binding • inhibin beta-A binding • inhibin beta-B binding
Cellular component	• cytoplasm • plasma membrane • plasma membrane • integral to plasma membrane • inhibin-betaglycan-ActRII complex
Biological process	• gastrulation with mouth forming second • positive regulation of protein phosphorylation • transmembrane receptor protein serine/threonine kinase signaling pathway • spermatogenesis • determination of left/right symmetry • mesoderm development • anterior/posterior pattern formation • response to organic substance • positive regulation of bone mineralization • BMP signaling pathway • BMP signaling pathway • BMP signaling pathway • regulation of BMP signaling pathway • positive regulation of activin receptor signaling pathway • sperm ejaculation • penile erection • positive regulation of erythrocyte differentiation • positive regulation of osteoblast differentiation • positive regulation of follicle-stimulating hormone secretion • embryonic skeletal system development • regulation of nitric-oxide synthase activity • Sertoli cell proliferation
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
148.6 – 148.69 Mb

Chr 2:
48.67 – 48.76 Mb

PubMed search

[1]

[2]

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

References

^ Donaldson CJ, Mathews LS, Vale WW (May 1992). "Molecular cloning and binding properties of the human type II activin receptor". Biochem Biophys Res Commun 184 (1): 310–316. doi:10.1016/0006-291X(92)91194-U. PMID 1314589.
^ Bondestam J, Horelli-Kuitunen N, Hilden K, Ritvos O, Aaltonen J (Apr 2000). "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): 219–220. doi:10.1159/000015429. PMID 10702675.
^ ^a ^b "Entrez Gene: ACVR2A activin A receptor, type IIA". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=92.
^ Lewis, K A; Gray P C, Blount A L, MacConell L A, Wiater E, Bilezikjian L M, Vale W (Mar. 2000). "Betaglycan binds inhibin and can mediate functional antagonism of activin signalling". Nature (ENGLAND) 404 (6776): 411–414. doi:10.1038/35006129. ISSN 0028-0836. PMID 10746731.
^ Martens, J W; de Winter J P, Timmerman M A, McLuskey A, van Schaik R H, Themmen A P, de Jong F H (Jul. 1997). "Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells". Endocrinology (UNITED STATES) 138 (7): 2928–2936. doi:10.1210/en.138.7.2928. ISSN 0013-7227. PMID 9202237.
^ Tsuchida, Kunihiro; Nakatani Masashi, Matsuzaki Takashi, Yamakawa Norio, Liu ZhongHui, Bao YongLi, Arai Koji Y, Murakami Tatsuya, Takehara Yuka, Kurisaki Akira, Sugino Hiromu (Oct. 2004). "Novel factors in regulation of activin signaling". Mol. Cell. Endocrinol. (Ireland) 225 (1–2): 1–8. doi:10.1016/j.mce.2004.02.006. ISSN 0303-7207. PMID 15451561.
^ Matsuzaki, Takashi; Hanai Sayuri, Kishi Hisashi, Liu ZhongHui, Bao YongLi, Kikuchi Akira, Tsuchida Kunihiro, Sugino Hiromu (May. 2002). "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway". J. Biol. Chem. (United States) 277 (21): 19008–19018. doi:10.1074/jbc.M112472200. ISSN 0021-9258. PMID 11882656.
^ Lebrun, J J; Takabe K, Chen Y, Vale W (Jan. 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. (UNITED STATES) 13 (1): 15–23. doi:10.1210/me.13.1.15. ISSN 0888-8809. PMID 9892009.
^ De Winter, J P; De Vries C J, Van Achterberg T A, Ameerun R F, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij A J (May. 1996). "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res. (UNITED STATES) 224 (2): 323–334. doi:10.1006/excr.1996.0142. ISSN 0014-4827. PMID 8612709.

Welt CK (2002). "The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction". Curr. Opin. Obstet. Gynecol. 14 (3): 317–323. doi:10.1097/00001703-200206000-00012. PMID 12032389.
Matzuk MM, Bradley A (1992). "Cloning of the human activin receptor cDNA reveals high evolutionary conservation". Biochim. Biophys. Acta 1130 (1): 105–8. PMID 1311955.
Mathews LS, Vale WW (1991). "Expression cloning of an activin receptor, a predicted transmembrane serine kinase". Cell 65 (6): 973–982. doi:10.1016/0092-8674(91)90549-E. PMID 1646080.
Xu J, McKeehan K, Matsuzaki K, McKeehan WL (1995). "Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism". J. Biol. Chem. 270 (11): 6308–6313. doi:10.1074/jbc.270.11.6308. PMID 7890768.
Attisano L, Cárcamo J, Ventura F et al. (1993). "Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors". Cell 75 (4): 671–680. doi:10.1016/0092-8674(93)90488-C. PMID 8242742.
Peng C, Huang TH, Jeung EB et al. (1994). "Expression of the type II activin receptor gene in the human placenta". Endocrinology 133 (6): 3046–3049. doi:10.1210/en.133.6.3046. PMID 8243335.
De Winter JP, De Vries CJ, Van Achterberg TA et al. (1996). "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res. 224 (2): 323–334. doi:10.1006/excr.1996.0142. PMID 8612709.
Attisano L, Wrana JL, Montalvo E, Massagué J (1996). "Activation of signalling by the activin receptor complex". Mol. Cell. Biol. 16 (3): 1066–73. PMC 231089. PMID 8622651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231089.
Liu QY, Niranjan B, Gomes P et al. (1996). "Inhibitory effects of activin on the growth and morpholgenesis of primary and transformed mammary epithelial cells". Cancer Res. 56 (5): 1155–63. PMID 8640777.
Nishitoh H, Ichijo H, Kimura M et al. (1996). "Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5". J. Biol. Chem. 271 (35): 21345–21352. doi:10.1074/jbc.271.35.21345. PMID 8702914.
Lebrun JJ, Vale WW (1997). "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. PMC 231893. PMID 9032295. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231893.
Macías-Silva M, Hoodless PA, Tang SJ et al. (1998). "Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2". J. Biol. Chem. 273 (40): 25628–25636. doi:10.1074/jbc.273.40.25628. PMID 9748228.
Barbara NP, Wrana JL, Letarte M (1999). "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): 584–594. doi:10.1074/jbc.274.2.584. PMID 9872992.
Lux A, Attisano L, Marchuk DA (1999). "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): 9984–9992. doi:10.1074/jbc.274.15.9984. PMID 10187774.
D'Abronzo FH, Swearingen B, Klibanski A, Alexander JM (1999). "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): 1716–1721. doi:10.1210/jc.84.5.1716. PMID 10323406.
Ebisawa T, Tada K, Kitajima I et al. (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci. 112 ( Pt 20): 3519–27. PMID 10504300.
van Schaik RH, Wierikx CD, Timmerman MA et al. (2000). "Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues". Br. J. Cancer 82 (1): 112–117. doi:10.1054/bjoc.1999.0886. PMC 2363208. PMID 10638976. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2363208.
Shoji H, Tsuchida K, Kishi H et al. (2000). "Identification and characterization of a PDZ protein that interacts with activin type II receptors". J. Biol. Chem. 275 (8): 5485–5492. doi:10.1074/jbc.275.8.5485. PMID 10681527.

PDB gallery

1bte: CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF THE TYPE II ACTIVIN RECEPTOR

1lx5: Crystal Structure of the BMP7/ActRII Extracellular Domain Complex

2goo: Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD

Cell signaling: TGF beta signaling pathway

TGF beta superfamily of ligands	TGF beta family (TGF-β1, TGF-β2, TGF-β3) Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15) Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15) Other (Activin and inhibin, Anti-müllerian hormone, Nodal)

TGF beta receptors (Activin, BMP)	TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) · ACVRL1 · BMPR1 (BMPR1A · BMPR1B) TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) · AMHR2 · BMPR2 TGFBR3: betaglycan

Transducers/SMAD	R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) · I-SMAD (SMAD6, SMAD7) · SMAD4

Ligand inhibitors	Cerberus · Chordin · DAN · Decorin · Follistatin · Gremlin · Lefty · LTBP1 · Noggin · THBS1

Coreceptors	BAMBI · Cripto

Other	SARA

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

ACVR2A

Interactions

References

Further reading