ID   AVR2B_RAT               Reviewed;         513 AA.
AC   P38445; Q4V8J8;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 3.
DT   08-NOV-2023, entry version 179.
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; Synonyms=Actriib;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1312838; DOI=10.1016/0006-291x(92)90535-s;
RA   Legerski R., Zhou X., Dresback J., Eberspaecher H., McKinney S.,
RA   Segarini P., de Crombrugghe B.;
RT   "Molecular cloning and characterization of a novel rat activin receptor.";
RL   Biochem. Biophys. Res. Commun. 183:672-679(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RX   PubMed=7916681; DOI=10.1210/endo.132.6.7916681;
RA   Feng Z.M., Madigan M.B., Chen C.L.C.;
RT   "Expression of type II activin receptor genes in the male and female
RT   reproductive tissues of the rat.";
RL   Endocrinology 132:2593-2600(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [4]
RP   X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 19-119 IN COMPLEX WITH HUMAN
RP   INHBA, AND DISULFIDE BONDS.
RX   PubMed=12660162; DOI=10.1093/emboj/cdg156;
RA   Thompson T.B., Woodruff T.K., Jardetzky T.S.;
RT   "Structures of an ActRIIB:activin A complex reveal a novel binding mode for
RT   TGF-beta ligand:receptor interactions.";
RL   EMBO J. 22:1555-1566(2003).
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. Interacts with BMP2. {ECO:0000250,
CC       ECO:0000250|UniProtKB:P27040}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q13705};
CC       Single-pass type I membrane protein {ECO:0000250}.
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; L10640; AAA40772.1; -; mRNA.
DR   EMBL; BC097358; AAH97358.1; -; mRNA.
DR   PIR; B49193; B49193.
DR   PIR; JQ1484; JQ1484.
DR   RefSeq; NP_113742.1; NM_031554.1.
DR   PDB; 1NYS; X-ray; 3.05 A; A/C=19-119.
DR   PDB; 1NYU; X-ray; 3.10 A; A/C=19-119.
DR   PDB; 6MAC; X-ray; 2.34 A; C=26-120.
DR   PDBsum; 1NYS; -.
DR   PDBsum; 1NYU; -.
DR   PDBsum; 6MAC; -.
DR   AlphaFoldDB; P38445; -.
DR   SMR; P38445; -.
DR   STRING; 10116.ENSRNOP00000019777; -.
DR   GlyCosmos; P38445; 2 sites, No reported glycans.
DR   GlyGen; P38445; 2 sites.
DR   PhosphoSitePlus; P38445; -.
DR   PaxDb; 10116-ENSRNOP00000019777; -.
DR   GeneID; 25366; -.
DR   KEGG; rno:25366; -.
DR   UCSC; RGD:2028; rat.
DR   AGR; RGD:2028; -.
DR   CTD; 93; -.
DR   RGD; 2028; Acvr2b.
DR   eggNOG; KOG3653; Eukaryota.
DR   InParanoid; P38445; -.
DR   OrthoDB; 3900892at2759; -.
DR   Reactome; R-RNO-1502540; Signaling by Activin.
DR   Reactome; R-RNO-201451; Signaling by BMP.
DR   EvolutionaryTrace; P38445; -.
DR   PRO; PR:P38445; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0048179; C:activin receptor complex; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR   GO; GO:0043235; C:receptor complex; ISO:RGD.
DR   GO; GO:0048185; F:activin binding; IDA:RGD.
DR   GO; GO:0017002; F:activin receptor activity; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019838; F:growth factor binding; ISO:RGD.
DR   GO; GO:0034711; F:inhibin binding; IDA:RGD.
DR   GO; GO:0019209; F:kinase activator activity; ISO:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR   GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
DR   GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; TAS:RGD.
DR   GO; GO:0032924; P:activin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
DR   GO; GO:0060840; P:artery development; ISO:RGD.
DR   GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR   GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR   GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR   GO; GO:0048617; P:embryonic foregut morphogenesis; ISO:RGD.
DR   GO; GO:0001702; P:gastrulation with mouth forming second; ISO:RGD.
DR   GO; GO:0007507; P:heart development; ISO:RGD.
DR   GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR   GO; GO:0001822; P:kidney development; ISO:RGD.
DR   GO; GO:0030324; P:lung development; ISO:RGD.
DR   GO; GO:0001946; P:lymphangiogenesis; ISO:RGD.
DR   GO; GO:0060836; P:lymphatic endothelial cell differentiation; ISO:RGD.
DR   GO; GO:0007498; P:mesoderm development; ISO:RGD.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISO:RGD.
DR   GO; GO:0035265; P:organ growth; ISO:RGD.
DR   GO; GO:0031016; P:pancreas development; ISO:RGD.
DR   GO; GO:0007389; P:pattern specification process; ISO:RGD.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0030501; P:positive regulation of bone mineralization; ISO:RGD.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR   GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0009966; P:regulation of signal transduction; ISO:RGD.
DR   GO; GO:0014823; P:response to activity; IEP:RGD.
DR   GO; GO:0009749; P:response to glucose; ISO:RGD.
DR   GO; GO:0061298; P:retina vasculature development in camera-type eye; ISO:RGD.
DR   GO; GO:0060021; P:roof of mouth development; ISO:RGD.
DR   GO; GO:0019953; P:sexual reproduction; NAS:RGD.
DR   GO; GO:0007165; P:signal transduction; ISO:RGD.
DR   GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR   GO; GO:0048705; P:skeletal system morphogenesis; ISO:RGD.
DR   GO; GO:0060841; P:venous blood vessel development; ISO:RGD.
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; IID50130; -.
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.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell membrane; Disulfide bond; Glycoprotein;
KW   Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW   Phosphoprotein; Receptor; Reference proteome;
KW   Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..513
FT                   /note="Activin receptor type-2B"
FT                   /id="PRO_0000024406"
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..513
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          190..481
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          492..513
FT                   /note="Interaction with DYNLT1"
FT                   /evidence="ECO:0000250|UniProtKB:P27040"
FT   ACT_SITE        322
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         196..204
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         217
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:0000269|PubMed:12660162,
FT                   ECO:0007744|PDB:1NYS, ECO:0007744|PDB:1NYU"
FT   DISULFID        49..77
FT                   /evidence="ECO:0000269|PubMed:12660162,
FT                   ECO:0007744|PDB:1NYS, ECO:0007744|PDB:1NYU"
FT   DISULFID        84..103
FT                   /evidence="ECO:0000269|PubMed:12660162,
FT                   ECO:0007744|PDB:1NYS, ECO:0007744|PDB:1NYU"
FT   DISULFID        90..102
FT                   /evidence="ECO:0000269|PubMed:12660162,
FT                   ECO:0007744|PDB:1NYS, ECO:0007744|PDB:1NYU"
FT   DISULFID        104..109
FT                   /evidence="ECO:0000269|PubMed:12660162,
FT                   ECO:0007744|PDB:1NYS, ECO:0007744|PDB:1NYU"
FT   CONFLICT        64
FT                   /note="R -> P (in Ref. 1; AAA40772 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        255
FT                   /note="Missing (in Ref. 2 and 3; AAH97358)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        488
FT                   /note="S -> G (in Ref. 1; AAA40772 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        501
FT                   /note="V -> S (in Ref. 1; AAA40772 and 2)"
FT                   /evidence="ECO:0000305"
FT   STRAND          27..33
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   HELIX           36..39
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          43..49
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          58..66
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          69..78
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   HELIX           82..84
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          89..92
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          94..96
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          98..106
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   TURN            107..110
FT                   /evidence="ECO:0007829|PDB:6MAC"
FT   STRAND          111..115
FT                   /evidence="ECO:0007829|PDB:6MAC"
SQ   SEQUENCE   513 AA;  57857 MW;  765DB33F11C64CA7 CRC64;
     MTAPWAALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE GEQDKRLHCY
     ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY FCCCEGNFCN ERFTHLPEPG
     GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS LIVLLAFWMY RHRKPPYGHV DIHEDPGPPP
     PSPLVGLKPL QLLEIKARGR FGCVWKAQLM NDFVAVKIFP LQDKQSWQSE REIFSTPGMK
     HENLLQFIAA EKRGCSNLEV ELWLITAFHD KGSLTDYLKG NIITWNELCH VAETMSRGLS
     YLHEDVPWCR GEGHKPSIAH RDFKSKNVLL KSDLTAVLAD FGLAVRFEPG KPPGDTHGQV
     GTRRYMAPEV LEGAINFQRD AFLRIDMYAM GLVLWELVSR CKAADGPVDE YMLPFEEEIG
     QHPSLEELQE VVVHKKMRPT IKDHWLKHPG LAQLCVTIEE CWDHDAEARL SAGCVEERVS
     LIRRSVNSST SDCLVSLVTS VTNVDLLPKE SSI
//