AVR2A_MOUSE
ID AVR2A_MOUSE Reviewed; 513 AA.
AC P27038;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Activin receptor type-2A;
DE EC=2.7.11.30;
DE AltName: Full=Activin receptor type IIA;
DE Short=ACTR-IIA;
DE Flags: Precursor;
GN Name=Acvr2a; Synonyms=Acvr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1646080; DOI=10.1016/0092-8674(91)90549-e;
RA Mathews L.S., Vale W.W.;
RT "Expression cloning of an activin receptor, a predicted transmembrane
RT serine kinase.";
RL Cell 65:973-982(1991).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-121.
RX PubMed=9886286; DOI=10.1038/4887;
RA Greenwald J., Fischer W.H., Vale W.W., Choe S.;
RT "Three-finger toxin fold for the extracellular ligand-binding domain of the
RT type II activin receptor serine kinase.";
RL Nat. Struct. Biol. 6:18-22(1999).
RN [3]
RP DISULFIDE BONDS IN EXTRACELLULAR DOMAIN.
RX PubMed=10449041; DOI=10.1023/a:1020640725959;
RA Fischer W.H., Greenwald J., Park M., Craig A.G., Choe S., Vale W.;
RT "The disulfide bond arrangement in the extracellular domain of the activin
RT type II receptor.";
RL J. Protein Chem. 18:437-446(1999).
RN [4]
RP INTERACTION WITH AIP1, AND IDENTIFICATION IN A COMPLEX WITH ACVR1B; AIP1
RP AND SMAD3.
RX PubMed=10681527; DOI=10.1074/jbc.275.8.5485;
RA Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z.,
RA Nakamura T., Sugino H.;
RT "Identification and characterization of a PDZ protein that interacts with
RT activin types II receptors.";
RL J. Biol. Chem. 275:5485-5492(2000).
RN [5]
RP FUNCTION.
RX PubMed=23527555; DOI=10.1111/febs.12256;
RA Wang S.S., Huang H.Y., Chen S.Z., Li X., Zhang W.T., Tang Q.Q.;
RT "Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the
RT adipocyte lineage.";
RL FEBS J. 280:2644-2651(2013).
CC -!- FUNCTION: On ligand binding, forms a receptor complex consisting of two
CC type II and two type I transmembrane serine/threonine kinases. Type II
CC receptors phosphorylate and activate type I receptors which
CC autophosphorylate, then bind and activate SMAD transcriptional
CC regulators. Receptor for activin A, activin B and inhibin A. Mediates
CC induction of adipogenesis by GDF6 (PubMed:23527555).
CC {ECO:0000269|PubMed:23527555}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with AIP1. Part of a complex consisting of AIP1,
CC ACVR2A, ACVR1B and SMAD3 (PubMed:10681527). Interacts with type I
CC receptor ACVR1 (By similarity). Interacts with BMP7 (By similarity).
CC {ECO:0000250|UniProtKB:P27037, ECO:0000269|PubMed:10681527}.
CC -!- INTERACTION:
CC P27038; P12643: BMP2; Xeno; NbExp=2; IntAct=EBI-1036102, EBI-1029262;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Brain, testis, intestine, liver and kidney.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; M65287; AAA37171.1; -; mRNA.
DR CCDS; CCDS16021.1; -.
DR PIR; A39896; A39896.
DR RefSeq; NP_031422.3; NM_007396.4.
DR PDB; 1BTE; X-ray; 1.50 A; A/B=25-121.
DR PDB; 1LX5; X-ray; 3.30 A; B=20-121.
DR PDB; 2GOO; X-ray; 2.20 A; C/F=20-121.
DR PDBsum; 1BTE; -.
DR PDBsum; 1LX5; -.
DR PDBsum; 2GOO; -.
DR AlphaFoldDB; P27038; -.
DR SMR; P27038; -.
DR BioGRID; 197955; 9.
DR CORUM; P27038; -.
DR DIP; DIP-5825N; -.
DR IntAct; P27038; 3.
DR STRING; 10090.ENSMUSP00000067305; -.
DR GlyGen; P27038; 2 sites.
DR iPTMnet; P27038; -.
DR PhosphoSitePlus; P27038; -.
DR MaxQB; P27038; -.
DR PaxDb; P27038; -.
DR PRIDE; P27038; -.
DR ProteomicsDB; 273507; -.
DR Antibodypedia; 18817; 478 antibodies from 38 providers.
DR DNASU; 11480; -.
DR Ensembl; ENSMUST00000063886; ENSMUSP00000067305; ENSMUSG00000052155.
DR GeneID; 11480; -.
DR KEGG; mmu:11480; -.
DR UCSC; uc008jpn.2; mouse.
DR CTD; 92; -.
DR MGI; MGI:102806; Acvr2a.
DR VEuPathDB; HostDB:ENSMUSG00000052155; -.
DR eggNOG; KOG3653; Eukaryota.
DR GeneTree; ENSGT00940000157233; -.
DR HOGENOM; CLU_000288_8_4_1; -.
DR InParanoid; P27038; -.
DR OMA; IICAFWV; -.
DR OrthoDB; 390511at2759; -.
DR PhylomeDB; P27038; -.
DR TreeFam; TF352876; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-1502540; Signaling by Activin.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR BioGRID-ORCS; 11480; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Acvr2a; mouse.
DR EvolutionaryTrace; P27038; -.
DR PRO; PR:P27038; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P27038; protein.
DR Bgee; ENSMUSG00000052155; Expressed in trigeminal ganglion and 273 other tissues.
DR ExpressionAtlas; P27038; baseline and differential.
DR Genevisible; P27038; MM.
DR GO; GO:0048179; C:activin receptor complex; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0034673; C:inhibin-betaglycan-ActRII complex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0048185; F:activin binding; IPI:MGI.
DR GO; GO:0017002; F:activin receptor activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0098821; F:BMP receptor activity; IMP:UniProtKB.
DR GO; GO:0015026; F:coreceptor activity; ISO:MGI.
DR GO; GO:0019838; F:growth factor binding; IMP:MGI.
DR GO; GO:0034711; F:inhibin binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IPI:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IGI:MGI.
DR GO; GO:0048706; P:embryonic skeletal system development; IMP:MGI.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IGI:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0007498; P:mesoderm development; IGI:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IGI:MGI.
DR GO; GO:0043084; P:penile erection; IMP:MGI.
DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:MGI.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:MGI.
DR GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IMP:MGI.
DR GO; GO:0009966; P:regulation of signal transduction; IDA:MGI.
DR GO; GO:0060011; P:Sertoli cell proliferation; IMP:MGI.
DR GO; GO:0042713; P:sperm ejaculation; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IGI:MGI.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR000472; Activin_recp.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00653; ACTIVIN2R.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Disulfide bond; Glycoprotein; Kinase; Magnesium;
KW Manganese; Membrane; Metal-binding; Nucleotide-binding; Receptor;
KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..513
FT /note="Activin receptor type-2A"
FT /id="PRO_0000024399"
FT TOPO_DOM 20..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..513
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 192..485
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 322
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 198..206
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 30..60
FT /evidence="ECO:0000269|PubMed:10449041"
FT DISULFID 50..78
FT /evidence="ECO:0000269|PubMed:10449041"
FT DISULFID 85..104
FT /evidence="ECO:0000269|PubMed:10449041"
FT DISULFID 91..103
FT /evidence="ECO:0000269|PubMed:10449041"
FT DISULFID 105..110
FT /evidence="ECO:0000269|PubMed:10449041"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:1BTE"
FT HELIX 37..40
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 70..79
FT /evidence="ECO:0007829|PDB:1BTE"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:2GOO"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:1BTE"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:1BTE"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:1BTE"
SQ SEQUENCE 513 AA; 57890 MW; 475CD292506BAC61 CRC64;
MGAAAKLAFA VFLISCSSGA ILGRSETQEC LFFNANWERD RTNQTGVEPC YGDKDKRRHC
FATWKNISGS IEIVKQGCWL DDINCYDRTD CIEKKDSPEV YFCCCEGNMC NEKFSYFPEM
EVTQPTSNPV TPKPPYYNIL LYSLVPLMLI AGIVICAFWV YRHHKMAYPP VLVPTQDPGP
PPPSPLLGLK PLQLLEVKAR GRFGCVWKAQ LLNEYVAVKI FPIQDKQSWQ NEYEVYSLPG
MKHENILQFI GAEKRGTSVD VDLWLITAFH EKGSLSDFLK ANVVSWNELC HIAETMARGL
AYLHEDIPGL KDGHKPAISH RDIKSKNVLL KNNLTACIAD FGLALKFEAG KSAGDTHGQV
GTRRYMAPEV LEGAINFQRD AFLRIDMYAM GLVLWELASR CTAADGPVDE YMLPFEEEIG
QHPSLEDMQE VVVHKKKRPV LRDYWQKHAG MAMLCETIEE CWDHDAEARL SAGCVGERIT
QMQRLTNIIT TEDIVTVVTM VTNVDFPPKE SSL
