GenomeNet

Database: UniProt
Entry: Q61271
LinkDB: Q61271
Original site: Q61271 
ID   ACV1B_MOUSE             Reviewed;         505 AA.
AC   Q61271;
DT   05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Activin receptor type-1B;
DE            EC=2.7.11.30;
DE   AltName: Full=Activin receptor type IB;
DE            Short=ACTR-IB;
DE   AltName: Full=Activin receptor-like kinase 4;
DE            Short=ALK-4;
DE   AltName: Full=Serine/threonine-protein kinase receptor R2;
DE            Short=SKR2;
DE   Flags: Precursor;
GN   Name=Acvr1b; Synonyms=Alk4;
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].
RC   STRAIN=NIH Swiss; TISSUE=Placenta;
RX   PubMed=7577669; DOI=10.1016/0925-4773(95)00395-h;
RA   Verschuern K., Dewulf N., Goumans M.J., Lonnoy O., Freijen A., Grimsby S.,
RA   Vande Spiegle K., ten Dijke P., Moren A., Vanscheeuwijck P., Heldin C.H.,
RA   Miyazono K., Mummery C., Van Den Eijnden-Van Raaij J., Huylebroeck D.;
RT   "Expression of type I and type IB receptors for activin in midgestation
RT   mouse embryos suggests distinct functions in organogensis.";
RL   Mech. Dev. 52:109-123(1995).
RN   [2]
RP   IDENTIFICATION IN A COMPLEX WITH MAGI2; ACVR2A; ACVR1B 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   [3]
RP   FUNCTION.
RX   PubMed=16885157; DOI=10.1074/jbc.m604959200;
RA   Muller M.R., Zheng F., Werner S., Alzheimer C.;
RT   "Transgenic mice expressing dominant-negative activin receptor IB in
RT   forebrain neurons reveal novel functions of activin at glutamatergic
RT   synapses.";
RL   J. Biol. Chem. 281:29076-29084(2006).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH TDP2.
RX   PubMed=18039968; DOI=10.1242/dev.000026;
RA   Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D.,
RA   Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D.,
RA   Huylebroeck D.;
RT   "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during
RT   zebrafish gastrulation and left-right axis determination.";
RL   Development 134:4381-4393(2007).
RN   [5]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=21191412; DOI=10.1038/jid.2010.400;
RA   Qiu W., Li X., Tang H., Huang A.S., Panteleyev A.A., Owens D.M., Su G.H.;
RT   "Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair
RT   loss abnormality.";
RL   J. Invest. Dermatol. 131:1067-1076(2011).
CC   -!- FUNCTION: Transmembrane serine/threonine kinase activin type-1 receptor
CC       forming an activin receptor complex with activin receptor type-2
CC       (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface
CC       to the cytoplasm and is thus regulating a many physiological and
CC       pathological processes including neuronal differentiation and neuronal
CC       survival, hair follicle development and cycling, FSH production by the
CC       pituitary gland, wound healing, extracellular matrix production,
CC       immunosuppression and carcinogenesis. Activin is also thought to have a
CC       paracrine or autocrine role in follicular development in the ovary.
CC       Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B)
CC       act as a primary activin receptors whereas the type-1 receptors like
CC       ACVR1B act as downstream transducers of activin signals. Activin binds
CC       to type-2 receptor at the plasma membrane and activates its serine-
CC       threonine kinase. The activated receptor type-2 then phosphorylates and
CC       activates the type-1 receptor such as ACVR1B. Once activated, the type-
CC       1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3,
CC       on serine residues of the C-terminal tail. Soon after their association
CC       with the activin receptor and subsequent phosphorylation, SMAD2 and
CC       SMAD3 are released into the cytoplasm where they interact with the
CC       common partner SMAD4. This SMAD complex translocates into the nucleus
CC       where it mediates activin-induced transcription. Inhibitory SMAD7,
CC       which is recruited to ACVR1B through FKBP1A, can prevent the
CC       association of SMAD2 and SMAD3 with the activin receptor complex,
CC       thereby blocking the activin signal. Activin signal transduction is
CC       also antagonized by the binding to the receptor of inhibin-B via the
CC       IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.
CC       {ECO:0000269|PubMed:16885157, ECO:0000269|PubMed:18039968}.
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   -!- ACTIVITY REGULATION: Activin receptor type-2 (ACVR2A or ACVR2B)
CC       activates the type-1 receptor through phosphorylation of its regulatory
CC       GS domain. {ECO:0000250}.
CC   -!- SUBUNIT: Forms an activin receptor complex with activin receptor type-2
CC       (ACVR2A or ACVR2B) (By similarity). Part of a complex consisting of
CC       MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:10681527). Interacts with
CC       SMAD2 and SMAD3 (By similarity). Interacts with SMAD7 (By similarity).
CC       Interacts with FKBP1A (By similarity). Interacts with IGSF1 (By
CC       similarity). Interacts with CRIPTO (By similarity). Interacts with TDP2
CC       (PubMed:18039968). Interacts with TSC22D1/TSC-22 (By similarity).
CC       {ECO:0000250|UniProtKB:P36896, ECO:0000269|PubMed:10681527,
CC       ECO:0000269|PubMed:18039968}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}.
CC   -!- DOMAIN: The GS domain is a 30-amino-acid sequence adjacent to the N-
CC       terminal boundary of the kinase domain and highly conserved in all
CC       other known type-1 receptors but not in type-2 receptors. The GS domain
CC       is the site of activation through phosphorylation by the II receptors
CC       (By similarity). {ECO:0000250}.
CC   -!- PTM: Autophosphorylated. Phosphorylated by activin receptor type-2
CC       (ACVR2A or ACVR2B) in response to activin-binding at serine and
CC       threonine residues in the GS domain. Phosphorylation of ACVR1B by
CC       activin receptor type-2 regulates association with SMAD7 (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-
CC       SMURF1 complex (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Leads to hair loss.
CC       {ECO:0000269|PubMed:21191412}.
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; Z31663; CAA83483.1; -; mRNA.
DR   CCDS; CCDS27846.1; -.
DR   RefSeq; NP_031421.1; NM_007395.3.
DR   AlphaFoldDB; Q61271; -.
DR   SMR; Q61271; -.
DR   BioGRID; 197954; 8.
DR   CORUM; Q61271; -.
DR   IntAct; Q61271; 2.
DR   MINT; Q61271; -.
DR   STRING; 10090.ENSMUSP00000000544; -.
DR   BindingDB; Q61271; -.
DR   GlyCosmos; Q61271; 1 site, No reported glycans.
DR   GlyGen; Q61271; 1 site.
DR   iPTMnet; Q61271; -.
DR   PhosphoSitePlus; Q61271; -.
DR   MaxQB; Q61271; -.
DR   PaxDb; 10090-ENSMUSP00000000544; -.
DR   ProteomicsDB; 281931; -.
DR   Antibodypedia; 14450; 621 antibodies from 37 providers.
DR   DNASU; 11479; -.
DR   Ensembl; ENSMUST00000000544.12; ENSMUSP00000000544.10; ENSMUSG00000000532.12.
DR   GeneID; 11479; -.
DR   KEGG; mmu:11479; -.
DR   UCSC; uc007xsr.1; mouse.
DR   AGR; MGI:1338944; -.
DR   CTD; 91; -.
DR   MGI; MGI:1338944; Acvr1b.
DR   VEuPathDB; HostDB:ENSMUSG00000000532; -.
DR   eggNOG; KOG2052; Eukaryota.
DR   GeneTree; ENSGT00940000157032; -.
DR   HOGENOM; CLU_000288_8_1_1; -.
DR   InParanoid; Q61271; -.
DR   OMA; VRNTHCC; -.
DR   OrthoDB; 3900892at2759; -.
DR   PhylomeDB; Q61271; -.
DR   TreeFam; TF314724; -.
DR   Reactome; R-MMU-1502540; Signaling by Activin.
DR   BioGRID-ORCS; 11479; 4 hits in 81 CRISPR screens.
DR   ChiTaRS; Acvr1b; mouse.
DR   PRO; PR:Q61271; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q61271; Protein.
DR   Bgee; ENSMUSG00000000532; Expressed in urinary bladder urothelium and 275 other cell types or tissues.
DR   ExpressionAtlas; Q61271; baseline and differential.
DR   Genevisible; Q61271; MM.
DR   GO; GO:0048179; C:activin receptor complex; ISO:MGI.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:0016361; F:activin receptor activity, type I; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0019838; F:growth factor binding; IEA:Ensembl.
DR   GO; GO:0070411; F:I-SMAD binding; ISO:MGI.
DR   GO; GO:0034711; F:inhibin binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR   GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; TAS:MGI.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR   GO; GO:0032924; P:activin receptor signaling pathway; IDA:MGI.
DR   GO; GO:0060936; P:cardiac fibroblast cell development; ISO:MGI.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:MGI.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:MGI.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0007498; P:mesoderm development; ISO:MGI.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR   GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR   GO; GO:0038092; P:nodal signaling pathway; ISO:MGI.
DR   GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO:MGI.
DR   GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR   GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:1901165; P:positive regulation of trophoblast cell migration; ISO: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:0007165; P:signal transduction; ISO:MGI.
DR   CDD; cd14143; STKc_TGFbR1_ACVR1b_ACVR1c; 1.
DR   Gene3D; 2.10.60.10; CD59; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR000472; Activin_recp.
DR   InterPro; IPR003605; GS_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR045860; Snake_toxin-like_sf.
DR   InterPro; IPR000333; TGFB_receptor.
DR   PANTHER; PTHR23255:SF22; ACTIVIN RECEPTOR TYPE-1B; 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   Pfam; PF08515; TGF_beta_GS; 1.
DR   SMART; SM00467; GS; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF57302; Snake toxin-like; 1.
DR   PROSITE; PS51256; GS; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Glycoprotein; Kinase; Magnesium; Manganese;
KW   Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor;
KW   Reference proteome; Serine/threonine-protein kinase; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..505
FT                   /note="Activin receptor type-1B"
FT                   /id="PRO_0000024418"
FT   TOPO_DOM        24..126
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        127..149
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        150..505
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          177..206
FT                   /note="GS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT   DOMAIN          207..497
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        335
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         213..221
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         234
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         380
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P36896"
FT   CARBOHYD        43
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   505 AA;  56700 MW;  56E9EEF1607A2517 CRC64;
     MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG ACMVSIFNLD
     GVEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF CNKIDLRVPS GHLKEPAHPS
     MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ
     DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE
     ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT
     IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH
     DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG
     GVHEDYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNVPNWW QSYEALRVMG KMMRECWYAN
     GAARLTALRI KKTLSQLSVQ EDVKI
//
DBGET integrated database retrieval system