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Q61271

- ACV1B_MOUSE

UniProt

Q61271 - ACV1B_MOUSE

Protein

Activin receptor type-1B

Gene

Acvr1b

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.2 Publications

    Catalytic activityi

    ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.

    Enzyme regulationi

    Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei234 – 2341ATPPROSITE-ProRule annotation
    Active sitei335 – 3351Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi213 – 2219ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. activin-activated receptor activity Source: Ensembl
    2. activin binding Source: MGI
    3. ATP binding Source: UniProtKB-KW
    4. metal ion binding Source: UniProtKB-KW
    5. protein binding Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. receptor signaling protein serine/threonine kinase activity Source: Ensembl
    8. transforming growth factor beta-activated receptor activity Source: InterPro
    9. transmembrane receptor protein serine/threonine kinase activity Source: MGI

    GO - Biological processi

    1. activin receptor signaling pathway Source: MGI
    2. cell surface receptor signaling pathway Source: MGI
    3. central nervous system development Source: Ensembl
    4. development of primary female sexual characteristics Source: Ensembl
    5. extrinsic apoptotic signaling pathway Source: Ensembl
    6. G1/S transition of mitotic cell cycle Source: Ensembl
    7. hair follicle development Source: MGI
    8. in utero embryonic development Source: MGI
    9. mesoderm development Source: MGI
    10. negative regulation of cell growth Source: Ensembl
    11. nodal signaling pathway Source: Ensembl
    12. peptidyl-threonine phosphorylation Source: UniProtKB
    13. positive regulation of activin receptor signaling pathway Source: Ensembl
    14. positive regulation of erythrocyte differentiation Source: Ensembl
    15. positive regulation of pathway-restricted SMAD protein phosphorylation Source: Ensembl
    16. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    17. positive regulation of trophoblast cell migration Source: Ensembl
    18. protein autophosphorylation Source: Ensembl
    19. regulation of signal transduction Source: MGI

    Keywords - Molecular functioni

    Kinase, Receptor, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_216258. Signaling by Activin.
    REACT_220645. Signaling by NODAL.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Activin receptor type-1B (EC:2.7.11.30)
    Alternative name(s):
    Activin receptor type IB
    Short name:
    ACTR-IB
    Activin receptor-like kinase 4
    Short name:
    ALK-4
    Serine/threonine-protein kinase receptor R2
    Short name:
    SKR2
    Gene namesi
    Name:Acvr1b
    Synonyms:Alk4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:1338944. Acvr1b.

    Subcellular locationi

    GO - Cellular componenti

    1. cell surface Source: Ensembl
    2. integral component of plasma membrane Source: MGI
    3. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Leads to hair loss.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 505482Activin receptor type-1BPRO_0000024418Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi43 – 431N-linked (GlcNAc...)Sequence Analysis
    Modified residuei380 – 3801PhosphotyrosineBy similarity

    Post-translational modificationi

    Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7 By similarity.By similarity
    Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex By similarity.By similarity
    Ubiquitinated.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ61271.
    PRIDEiQ61271.

    PTM databases

    PhosphoSiteiQ61271.

    Expressioni

    Gene expression databases

    ArrayExpressiQ61271.
    BgeeiQ61271.
    CleanExiMM_ACVR1B.
    GenevestigatoriQ61271.

    Interactioni

    Subunit structurei

    Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Interacts with TDP2 By similarity. Interacts with AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi197954. 2 interactions.
    IntActiQ61271. 1 interaction.
    MINTiMINT-2842316.

    Structurei

    3D structure databases

    ProteinModelPortaliQ61271.
    SMRiQ61271. Positions 31-104, 149-501.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 126103ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini150 – 505356CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei127 – 14923HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini177 – 20630GSPROSITE-ProRule annotationAdd
    BLAST
    Domaini207 – 497291Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors By similarity.By similarity

    Sequence similaritiesi

    Contains 1 GS domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110337.
    HOGENOMiHOG000230587.
    HOVERGENiHBG054502.
    InParanoidiQ61271.
    KOiK13567.
    OMAiQCACTSC.
    OrthoDBiEOG7Q8CN3.
    PhylomeDBiQ61271.
    TreeFamiTF314724.

    Family and domain databases

    InterProiIPR000472. Activin_rcpt.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    IPR003605. TGF_beta_rcpt_GS.
    IPR000333. TGFB_receptor.
    [Graphical view]
    PANTHERiPTHR23255. PTHR23255. 1 hit.
    PfamiPF01064. Activin_recp. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF08515. TGF_beta_GS. 1 hit.
    [Graphical view]
    SMARTiSM00467. GS. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS51256. GS. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q61271-1 [UniParc]FASTAAdd to Basket

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    MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG    50
    ACMVSIFNLD GVEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF 100
    CNKIDLRVPS GHLKEPAHPS MWGPVELVGI IAGPVFLLFL IIIIVFLVIN 150
    YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ DLVYDLSTSG SGSGLPLFVQ 200
    RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE ERSWFREAEI 250
    YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 300
    IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA 350
    IADLGLAVRH DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC 400
    ADIYALGLVY WEIARRCNSG GVHEDYQLPY YDLVPSDPSI EEMRKVVCDQ 450
    KLRPNVPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ 500
    EDVKI 505
    Length:505
    Mass (Da):56,700
    Last modified:November 1, 1996 - v1
    Checksum:i56E9EEF1607A2517
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z31663 mRNA. Translation: CAA83483.1.
    CCDSiCCDS27846.1.
    RefSeqiNP_031421.1. NM_007395.3.
    UniGeneiMm.308467.

    Genome annotation databases

    EnsembliENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532.
    GeneIDi11479.
    KEGGimmu:11479.
    UCSCiuc007xsr.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z31663 mRNA. Translation: CAA83483.1 .
    CCDSi CCDS27846.1.
    RefSeqi NP_031421.1. NM_007395.3.
    UniGenei Mm.308467.

    3D structure databases

    ProteinModelPortali Q61271.
    SMRi Q61271. Positions 31-104, 149-501.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 197954. 2 interactions.
    IntActi Q61271. 1 interaction.
    MINTi MINT-2842316.

    PTM databases

    PhosphoSitei Q61271.

    Proteomic databases

    PaxDbi Q61271.
    PRIDEi Q61271.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000000544 ; ENSMUSP00000000544 ; ENSMUSG00000000532 .
    GeneIDi 11479.
    KEGGi mmu:11479.
    UCSCi uc007xsr.1. mouse.

    Organism-specific databases

    CTDi 91.
    MGIi MGI:1338944. Acvr1b.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110337.
    HOGENOMi HOG000230587.
    HOVERGENi HBG054502.
    InParanoidi Q61271.
    KOi K13567.
    OMAi QCACTSC.
    OrthoDBi EOG7Q8CN3.
    PhylomeDBi Q61271.
    TreeFami TF314724.

    Enzyme and pathway databases

    Reactomei REACT_216258. Signaling by Activin.
    REACT_220645. Signaling by NODAL.

    Miscellaneous databases

    NextBioi 278824.
    PROi Q61271.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61271.
    Bgeei Q61271.
    CleanExi MM_ACVR1B.
    Genevestigatori Q61271.

    Family and domain databases

    InterProi IPR000472. Activin_rcpt.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    IPR003605. TGF_beta_rcpt_GS.
    IPR000333. TGFB_receptor.
    [Graphical view ]
    PANTHERi PTHR23255. PTHR23255. 1 hit.
    Pfami PF01064. Activin_recp. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF08515. TGF_beta_GS. 1 hit.
    [Graphical view ]
    SMARTi SM00467. GS. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS51256. GS. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Expression of type I and type IB receptors for activin in midgestation mouse embryos suggests distinct functions in organogensis."
      Verschuern K., Dewulf N., Goumans M.J., Lonnoy O., Freijen A., Grimsby S., Vande Spiegle K., ten Dijke P., Moren A., Vanscheeuwijck P., Heldin C.H., Miyazono K., Mummery C., Van Den Eijnden-Van Raaij J., Huylebroeck D.
      Mech. Dev. 52:109-123(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: NIH Swiss.
      Tissue: Placenta.
    2. "Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses."
      Muller M.R., Zheng F., Werner S., Alzheimer C.
      J. Biol. Chem. 281:29076-29084(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    3. "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination."
      Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., Huylebroeck D.
      Development 134:4381-4393(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TDP2.
    4. "Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair loss abnormality."
      Qiu W., Li X., Tang H., Huang A.S., Panteleyev A.A., Owens D.M., Su G.H.
      J. Invest. Dermatol. 131:1067-1076(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiACV1B_MOUSE
    AccessioniPrimary (citable) accession number: Q61271
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2004
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 128 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3