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P27040

- AVR2B_MOUSE

UniProt

P27040 - AVR2B_MOUSE

Protein

Activin receptor type-2B

Gene

Acvr2b

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      Previous versions | rss
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    Functioni

    Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating 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, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). 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. 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 By similarity.By similarity

    Catalytic activityi

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

    Cofactori

    Magnesium or manganese.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei241 – 2411ATPPROSITE-ProRule annotation
    Active sitei345 – 3451Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi220 – 2289ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. activation of protein kinase activity Source: MGI
    2. anterior/posterior pattern specification Source: MGI
    3. artery development Source: BHF-UCL
    4. blood vessel remodeling Source: BHF-UCL
    5. BMP signaling pathway Source: Ensembl
    6. determination of left/right symmetry Source: MGI
    7. embryonic foregut morphogenesis Source: MGI
    8. gastrulation with mouth forming second Source: MGI
    9. heart development Source: MGI
    10. insulin secretion Source: MGI
    11. kidney development Source: MGI
    12. lung development Source: MGI
    13. lymphangiogenesis Source: BHF-UCL
    14. lymphatic endothelial cell differentiation Source: BHF-UCL
    15. mesoderm development Source: MGI
    16. odontogenesis of dentin-containing tooth Source: MGI
    17. organ growth Source: MGI
    18. palate development Source: MGI
    19. pancreas development Source: MGI
    20. pattern specification process Source: MGI
    21. positive regulation of activin receptor signaling pathway Source: Ensembl
    22. positive regulation of bone mineralization Source: Ensembl
    23. positive regulation of osteoblast differentiation Source: Ensembl
    24. post-embryonic development Source: MGI
    25. regulation of signal transduction Source: MGI
    26. response to glucose Source: MGI
    27. retina vasculature development in camera-type eye Source: BHF-UCL
    28. skeletal system development Source: MGI
    29. skeletal system morphogenesis Source: MGI
    30. venous blood vessel development Source: BHF-UCL

    Keywords - Molecular functioni

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

    Keywords - Ligandi

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

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 3474.
    ReactomeiREACT_216258. Signaling by Activin.
    REACT_220505. Signaling by BMP.
    REACT_220645. Signaling by NODAL.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Activin receptor type-2B (EC:2.7.11.30)
    Alternative name(s):
    Activin receptor type IIB
    Short name:
    ACTR-IIB
    Gene namesi
    Name:Acvr2b
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:87912. Acvr2b.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: Reactome
    4. protein complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 536518Activin receptor type-2BPRO_0000024405Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi29 ↔ 59
    Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi49 ↔ 77
    Glycosylationi65 – 651N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi84 ↔ 103
    Disulfide bondi90 ↔ 102
    Disulfide bondi104 ↔ 109

    Post-translational modificationi

    Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiP27040.

    PTM databases

    PhosphoSiteiP27040.

    Expressioni

    Gene expression databases

    BgeeiP27040.
    CleanExiMM_ACVR2B.
    GenevestigatoriP27040.

    Interactioni

    Subunit structurei

    Forms an activin receptor complex with activin type II receptors such as ACVR1B. Interacts with VPS39.By similarity

    Protein-protein interaction databases

    BioGridi197956. 1 interaction.
    DIPiDIP-5799N.
    IntActiP27040. 1 interaction.
    MINTiMINT-2842249.
    STRINGi10090.ENSMUSP00000035093.

    Structurei

    Secondary structure

    1
    536
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi28 – 336
    Turni34 – 407
    Beta strandi43 – 486
    Beta strandi57 – 6610
    Beta strandi69 – 7911
    Helixi82 – 843
    Beta strandi88 – 925
    Beta strandi93 – 964
    Beta strandi98 – 1069
    Turni107 – 1104
    Beta strandi111 – 1155

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1S4YX-ray2.30A/C23-120[»]
    2H64X-ray1.92C19-117[»]
    ProteinModelPortaliP27040.
    SMRiP27040. Positions 24-116, 214-536.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27040.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 137119ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini159 – 536378CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei138 – 15821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini214 – 504291Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00560000076906.
    HOGENOMiHOG000231495.
    HOVERGENiHBG054502.
    InParanoidiP27040.
    KOiK13596.
    OMAiKKMRPAI.
    OrthoDBiEOG7JHM5B.
    PhylomeDBiP27040.
    TreeFamiTF352876.

    Family and domain databases

    InterProiIPR000472. Activin_rcpt.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR000333. TGFB_receptor.
    [Graphical view]
    PANTHERiPTHR23255. PTHR23255. 1 hit.
    PfamiPF01064. Activin_recp. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR00653. ACTIVIN2R.
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Note: ActR-IIB1 and ActR-IIB2 have similar but higher affinities for activin A than ActR-II, ActR-IIB3 and ActR-IIB4.

    Isoform ActR-IIB1 (identifier: P27040-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MTAPWAALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE    50
    GEQDKRLHCY ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY 100
    FCCCEGNFCN ERFTHLPEPG GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS 150
    LIVLLAFWMY RHRKPPYGHV DIHEVRQCQR WAGRRDGCAD SFKPLPFQDP 200
    GPPPPSPLVG LKPLQLLEIK ARGRFGCVWK AQLMNDFVAV KIFPLQDKQS 250
    WQSEREIFST PGMKHENLLQ FIAAEKRGSN LEVELWLITA FHDKGSLTDY 300
    LKGNIITWNE LCHVAETMSR GLSYLHEDVP WCRGEGHKPS IAHRDFKSKN 350
    VLLKSDLTAV LADFGLAVRF EPGKPPGDTH GQVGTRRYMA PEVLEGAINF 400
    QRDAFLRIDM YAMGLVLWEL VSRCKAADGP VDEYMLPFEE EIGQHPSLEE 450
    LQEVVVHKKM RPTIKDHWLK HPGLAQLCVT IEECWDHDAE ARLSAGCVEE 500
    RVSLIRRSVN GTTSDCLVSL VTSVTNVDLL PKESSI 536
    Length:536
    Mass (Da):60,542
    Last modified:August 1, 1992 - v1
    Checksum:iBF1C8CAC974BF5E2
    GO
    Isoform ActR-IIB2 (identifier: P27040-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         175-198: Missing.

    Show »
    Length:512
    Mass (Da):57,738
    Checksum:iF8C53AE6D0825D7A
    GO
    Isoform ActR-IIB3 (identifier: P27040-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         124-131: Missing.

    Show »
    Length:528
    Mass (Da):59,657
    Checksum:i1559B59DEAF7733B
    GO
    Isoform ActR-IIB4 (identifier: P27040-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         124-131: Missing.
         175-198: Missing.

    Show »
    Length:504
    Mass (Da):56,853
    Checksum:i42A315009EE8C17A
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei124 – 1318Missing in isoform ActR-IIB3 and isoform ActR-IIB4. 1 PublicationVSP_004951
    Alternative sequencei175 – 19824Missing in isoform ActR-IIB2 and isoform ActR-IIB4. 2 PublicationsVSP_004952Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84120 mRNA. Translation: AAA37172.1.
    BC106189 mRNA. Translation: AAI06190.1.
    CCDSiCCDS23615.1. [P27040-1]
    PIRiA40829.
    B40829.
    C40829.
    D40829.
    RefSeqiNP_031423.1. NM_007397.2. [P27040-1]
    XP_006511988.1. XM_006511925.1. [P27040-2]
    XP_006511989.1. XM_006511926.1. [P27040-4]
    UniGeneiMm.390239.

    Genome annotation databases

    EnsembliENSMUST00000035093; ENSMUSP00000035093; ENSMUSG00000061393. [P27040-3]
    ENSMUST00000165044; ENSMUSP00000126108; ENSMUSG00000061393. [P27040-1]
    GeneIDi11481.
    KEGGimmu:11481.
    UCSCiuc009sax.1. mouse. [P27040-1]
    uc009say.1. mouse. [P27040-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84120 mRNA. Translation: AAA37172.1 .
    BC106189 mRNA. Translation: AAI06190.1 .
    CCDSi CCDS23615.1. [P27040-1 ]
    PIRi A40829.
    B40829.
    C40829.
    D40829.
    RefSeqi NP_031423.1. NM_007397.2. [P27040-1 ]
    XP_006511988.1. XM_006511925.1. [P27040-2 ]
    XP_006511989.1. XM_006511926.1. [P27040-4 ]
    UniGenei Mm.390239.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1S4Y X-ray 2.30 A/C 23-120 [» ]
    2H64 X-ray 1.92 C 19-117 [» ]
    ProteinModelPortali P27040.
    SMRi P27040. Positions 24-116, 214-536.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 197956. 1 interaction.
    DIPi DIP-5799N.
    IntActi P27040. 1 interaction.
    MINTi MINT-2842249.
    STRINGi 10090.ENSMUSP00000035093.

    PTM databases

    PhosphoSitei P27040.

    Proteomic databases

    PRIDEi P27040.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000035093 ; ENSMUSP00000035093 ; ENSMUSG00000061393 . [P27040-3 ]
    ENSMUST00000165044 ; ENSMUSP00000126108 ; ENSMUSG00000061393 . [P27040-1 ]
    GeneIDi 11481.
    KEGGi mmu:11481.
    UCSCi uc009sax.1. mouse. [P27040-1 ]
    uc009say.1. mouse. [P27040-2 ]

    Organism-specific databases

    CTDi 93.
    MGIi MGI:87912. Acvr2b.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00560000076906.
    HOGENOMi HOG000231495.
    HOVERGENi HBG054502.
    InParanoidi P27040.
    KOi K13596.
    OMAi KKMRPAI.
    OrthoDBi EOG7JHM5B.
    PhylomeDBi P27040.
    TreeFami TF352876.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 3474.
    Reactomei REACT_216258. Signaling by Activin.
    REACT_220505. Signaling by BMP.
    REACT_220645. Signaling by NODAL.

    Miscellaneous databases

    EvolutionaryTracei P27040.
    NextBioi 278832.
    PROi P27040.
    SOURCEi Search...

    Gene expression databases

    Bgeei P27040.
    CleanExi MM_ACVR2B.
    Genevestigatori P27040.

    Family and domain databases

    InterProi IPR000472. Activin_rcpt.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR000333. TGFB_receptor.
    [Graphical view ]
    PANTHERi PTHR23255. PTHR23255. 1 hit.
    Pfami PF01064. Activin_recp. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PRINTSi PR00653. ACTIVIN2R.
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors."
      Attisano L., Wrana J.L., Cheifetz S., Massague J.
      Cell 68:97-108(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ACTR-IIB1; ACTR-IIB2; ACTR-IIB3 AND ACTR-IIB4).
      Strain: BALB/c.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ACTR-IIB2).
      Tissue: Jaw.

    Entry informationi

    Entry nameiAVR2B_MOUSE
    AccessioniPrimary (citable) accession number: P27040
    Secondary accession number(s): Q3KQI1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 150 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

    3D-structure, Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3