AVR2B_RAT
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 03-AUG-2022, entry version 174.
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}.
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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 GlyGen; P38445; 2 sites.
DR PhosphoSitePlus; P38445; -.
DR PaxDb; P38445; -.
DR PRIDE; P38445; -.
DR GeneID; 25366; -.
DR KEGG; rno:25366; -.
DR UCSC; RGD:2028; rat.
DR CTD; 93; -.
DR RGD; 2028; Acvr2b.
DR eggNOG; KOG3653; Eukaryota.
DR InParanoid; P38445; -.
DR OrthoDB; 390511at2759; -.
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: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:0032147; P:activation of protein kinase activity; ISO: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: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:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO: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 Gene3D; 2.10.60.10; -; 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; PTHR23255; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00653; ACTIVIN2R.
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; 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
