ID AVR2B_MOUSE Reviewed; 536 AA. AC P27040; Q3KQI1; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 27-MAR-2024, entry version 208. DE RecName: Full=Activin receptor type-2B; DE EC=2.7.11.30; DE AltName: Full=Activin receptor type IIB; DE Short=ACTR-IIB; DE Flags: Precursor; GN Name=Acvr2b; 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] (ISOFORMS ACTR-IIB1; ACTR-IIB2; ACTR-IIB3 AND RP ACTR-IIB4). RC STRAIN=BALB/cJ; RX PubMed=1310075; DOI=10.1016/0092-8674(92)90209-u; RA Attisano L., Wrana J.L., Cheifetz S., Massague J.; RT "Novel activin receptors: distinct genes and alternative mRNA splicing RT generate a repertoire of serine/threonine kinase receptors."; RL Cell 68:97-108(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ACTR-IIB2). RC TISSUE=Jaw; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP INTERACTION WITH DYNLT. RX PubMed=27502274; DOI=10.1074/jbc.m116.736884; RA Merino-Gracia J., Zamora-Carreras H., Bruix M., Rodriguez-Crespo I.; RT "Molecular basis for the protein recognition specificity of the dynein RT light chain DYNLT1/Tctex1: characterization of the interaction with activin RT receptor IIB."; RL J. Biol. Chem. 291:20962-20975(2016). RN [4] RP INTERACTION WITH BMP3. RX PubMed=22074949; DOI=10.1210/me.2011-1168; RA Kokabu S., Gamer L., Cox K., Lowery J., Tsuji K., Raz R., Economides A., RA Katagiri T., Rosen V.; RT "BMP3 suppresses osteoblast differentiation of bone marrow stromal cells RT via interaction with Acvr2b."; RL Mol. Endocrinol. 26:87-94(2012). CC -!- FUNCTION: Transmembrane serine/threonine kinase activin type-2 receptor CC forming an activin receptor complex with activin type-1 CC serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces CC the activin signal from the cell surface to the cytoplasm and is thus CC regulating many physiological and pathological processes including CC neuronal differentiation and neuronal survival, hair follicle CC development and cycling, FSH production by the pituitary gland, wound CC healing, extracellular matrix production, immunosuppression and CC carcinogenesis. Activin is also thought to have a paracrine or CC autocrine role in follicular development in the ovary. Within the CC receptor complex, the type-2 receptors act as a primary activin CC receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin- CC A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream CC transducers of activin signals. Activin binds to type-2 receptor at the CC plasma membrane and activates its serine-threonine kinase. The CC activated receptor type-2 then phosphorylates and activates the type-1 CC receptor. Once activated, the type-1 receptor binds and phosphorylates CC the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal CC tail. Soon after their association with the activin receptor and CC subsequent phosphorylation, SMAD2 and SMAD3 are released into the CC cytoplasm where they interact with the common partner SMAD4. This SMAD CC complex translocates into the nucleus where it mediates activin-induced CC transcription. Inhibitory SMAD7, which is recruited to ACVR1B through CC FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin CC receptor complex, thereby blocking the activin signal. Activin signal CC transduction is also antagonized by the binding to the receptor of CC inhibin-B via the IGSF1 inhibin coreceptor (By similarity). CC {ECO:0000250}. 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: Forms an activin receptor complex with activin type II CC receptors such as ACVR1B. Interacts with VPS39. Interacts with DYNLT1. CC Interacts with BMP3 (PubMed:22074949). Interacts with BMP2 (By CC similarity). Interacts with BMP6 (By similarity). CC {ECO:0000250|UniProtKB:Q13705, ECO:0000269|PubMed:22074949, CC ECO:0000269|PubMed:27502274}. CC -!- INTERACTION: CC P27040; P36896: ACVR1B; Xeno; NbExp=4; IntAct=EBI-8571194, EBI-1384128; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q13705}; CC Single-pass type I membrane protein {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=ActR-IIB1 and ActR-IIB2 have similar but higher affinities CC for activin A than ActR-II, ActR-IIB3 and ActR-IIB4.; CC Name=ActR-IIB1; CC IsoId=P27040-1; Sequence=Displayed; CC Name=ActR-IIB2; CC IsoId=P27040-2; Sequence=VSP_004952; CC Name=ActR-IIB3; CC IsoId=P27040-3; Sequence=VSP_004951; CC Name=ActR-IIB4; CC IsoId=P27040-4; Sequence=VSP_004951, VSP_004952; CC -!- PTM: Phosphorylated. Constitutive phosphorylation is in part catalyzed CC by its own kinase activity (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M84120; AAA37172.1; -; mRNA. DR EMBL; BC106189; AAI06190.1; -; mRNA. DR CCDS; CCDS23615.1; -. [P27040-1] DR CCDS; CCDS90681.1; -. [P27040-2] DR PIR; A40829; A40829. DR PIR; B40829; B40829. DR PIR; C40829; C40829. DR PIR; D40829; D40829. DR RefSeq; NP_001300686.1; NM_001313757.1. [P27040-2] DR RefSeq; NP_031423.1; NM_007397.3. [P27040-1] DR RefSeq; XP_006511989.1; XM_006511926.3. [P27040-4] DR PDB; 1S4Y; X-ray; 2.30 A; A/C=23-120. DR PDB; 2H64; X-ray; 1.92 A; C=19-117. DR PDBsum; 1S4Y; -. DR PDBsum; 2H64; -. DR AlphaFoldDB; P27040; -. DR SMR; P27040; -. DR BioGRID; 197956; 4. DR DIP; DIP-5799N; -. DR IntAct; P27040; 5. DR MINT; P27040; -. DR STRING; 10090.ENSMUSP00000126108; -. DR GlyCosmos; P27040; 2 sites, No reported glycans. DR GlyGen; P27040; 2 sites. DR PhosphoSitePlus; P27040; -. DR MaxQB; P27040; -. DR PaxDb; 10090-ENSMUSP00000126108; -. DR Antibodypedia; 12076; 520 antibodies from 33 providers. DR DNASU; 11481; -. DR Ensembl; ENSMUST00000035093.15; ENSMUSP00000035093.9; ENSMUSG00000061393.15. [P27040-3] DR Ensembl; ENSMUST00000165044.3; ENSMUSP00000126108.2; ENSMUSG00000061393.15. [P27040-1] DR Ensembl; ENSMUST00000215746.2; ENSMUSP00000150566.2; ENSMUSG00000061393.15. [P27040-2] DR GeneID; 11481; -. DR KEGG; mmu:11481; -. DR UCSC; uc009sax.1; mouse. [P27040-1] DR UCSC; uc009say.1; mouse. [P27040-2] DR AGR; MGI:87912; -. DR CTD; 93; -. DR MGI; MGI:87912; Acvr2b. DR VEuPathDB; HostDB:ENSMUSG00000061393; -. DR eggNOG; KOG3653; Eukaryota. DR GeneTree; ENSGT00940000156210; -. DR HOGENOM; CLU_000288_8_4_1; -. DR InParanoid; P27040; -. DR OMA; SWNDLCH; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P27040; -. 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; 11481; 3 hits in 81 CRISPR screens. DR ChiTaRS; Acvr2b; mouse. DR EvolutionaryTrace; P27040; -. DR PRO; PR:P27040; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P27040; Protein. DR Bgee; ENSMUSG00000061393; Expressed in rostral migratory stream and 247 other cell types or tissues. DR GO; GO:0048179; C:activin receptor complex; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0048185; F:activin binding; IDA:MGI. DR GO; GO:0017002; F:activin receptor activity; IBA:GO_Central. DR GO; GO:0016362; F:activin receptor activity, type II; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019838; F:growth factor binding; IMP:MGI. DR GO; GO:0034711; F:inhibin binding; ISO:MGI. DR GO; GO:0019209; F:kinase activator activity; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI. DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI. DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI. DR GO; GO:0060840; P:artery development; IMP:BHF-UCL. DR GO; GO:0001974; P:blood vessel remodeling; IMP:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; 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; IMP:MGI. DR GO; GO:0048617; P:embryonic foregut morphogenesis; IMP:MGI. DR GO; GO:0001702; P:gastrulation with mouth forming second; IGI:MGI. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0030073; P:insulin secretion; IGI:MGI. DR GO; GO:0001822; P:kidney development; IMP:MGI. DR GO; GO:0030324; P:lung development; IGI:MGI. DR GO; GO:0001946; P:lymphangiogenesis; IMP:BHF-UCL. DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; IMP:BHF-UCL. DR GO; GO:0007498; P:mesoderm development; IGI:MGI. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI. DR GO; GO:0035265; P:organ growth; IGI:MGI. DR GO; GO:0031016; P:pancreas development; IGI:MGI. DR GO; GO:0007389; P:pattern specification process; IGI:MGI. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. 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:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI. DR GO; GO:0009791; P:post-embryonic development; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0009966; P:regulation of signal transduction; IDA:MGI. DR GO; GO:0009749; P:response to glucose; IGI:MGI. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IMP:BHF-UCL. DR GO; GO:0060021; P:roof of mouth development; IMP:MGI. DR GO; GO:0007165; P:signal transduction; ISO:MGI. DR GO; GO:0001501; P:skeletal system development; IMP:MGI. DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI. DR GO; GO:0060841; P:venous blood vessel development; IMP:BHF-UCL. DR CDD; cd14140; STKc_ACVR2b; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID50131; -. 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:SF70; ACTIVIN RECEPTOR TYPE-2B; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR00653; ACTIVIN2R. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P27040; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Disulfide bond; Glycoprotein; Kinase; Magnesium; Manganese; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..536 FT /note="Activin receptor type-2B" FT /id="PRO_0000024405" FT TOPO_DOM 19..137 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 138..158 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 159..536 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 214..504 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 515..536 FT /note="Interaction with DYNLT1" FT /evidence="ECO:0000269|PubMed:27502274" FT ACT_SITE 345 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 220..228 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 241 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT CARBOHYD 42 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 65 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 29..59 FT /evidence="ECO:0000250|UniProtKB:P38445" FT DISULFID 49..77 FT /evidence="ECO:0000250|UniProtKB:P38445" FT DISULFID 84..103 FT /evidence="ECO:0000250|UniProtKB:P38445" FT DISULFID 90..102 FT /evidence="ECO:0000250|UniProtKB:P38445" FT DISULFID 104..109 FT /evidence="ECO:0000250|UniProtKB:P38445" FT VAR_SEQ 124..131 FT /note="Missing (in isoform ActR-IIB3 and isoform FT ActR-IIB4)" FT /evidence="ECO:0000303|PubMed:1310075" FT /id="VSP_004951" FT VAR_SEQ 175..198 FT /note="Missing (in isoform ActR-IIB2 and isoform FT ActR-IIB4)" FT /evidence="ECO:0000303|PubMed:1310075, FT ECO:0000303|PubMed:15489334" FT /id="VSP_004952" FT STRAND 28..33 FT /evidence="ECO:0007829|PDB:2H64" FT TURN 34..40 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 43..48 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 57..66 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 69..79 FT /evidence="ECO:0007829|PDB:2H64" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 88..92 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:1S4Y" FT STRAND 98..106 FT /evidence="ECO:0007829|PDB:2H64" FT TURN 107..110 FT /evidence="ECO:0007829|PDB:2H64" FT STRAND 111..115 FT /evidence="ECO:0007829|PDB:2H64" SQ SEQUENCE 536 AA; 60542 MW; BF1C8CAC974BF5E2 CRC64; MTAPWAALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE GEQDKRLHCY ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY FCCCEGNFCN ERFTHLPEPG GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS LIVLLAFWMY RHRKPPYGHV DIHEVRQCQR WAGRRDGCAD SFKPLPFQDP GPPPPSPLVG LKPLQLLEIK ARGRFGCVWK AQLMNDFVAV KIFPLQDKQS WQSEREIFST PGMKHENLLQ FIAAEKRGSN LEVELWLITA FHDKGSLTDY LKGNIITWNE LCHVAETMSR GLSYLHEDVP WCRGEGHKPS IAHRDFKSKN VLLKSDLTAV LADFGLAVRF EPGKPPGDTH GQVGTRRYMA PEVLEGAINF QRDAFLRIDM YAMGLVLWEL VSRCKAADGP VDEYMLPFEE EIGQHPSLEE LQEVVVHKKM RPTIKDHWLK HPGLAQLCVT IEECWDHDAE ARLSAGCVEE RVSLIRRSVN GTTSDCLVSL VTSVTNVDLL PKESSI //