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P25322

- CCND1_MOUSE

UniProt

P25322 - CCND1_MOUSE

Protein

G1/S-specific cyclin-D1

Gene

Ccnd1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (01 May 1992)
      Previous versions | rss
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    Functioni

    Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner By similarity.By similarity

    GO - Molecular functioni

    1. cyclin-dependent protein serine/threonine kinase regulator activity Source: MGI
    2. kinase activity Source: MGI
    3. protein binding Source: UniProtKB
    4. protein kinase activity Source: MGI
    5. protein kinase binding Source: UniProtKB
    6. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

    1. canonical Wnt signaling pathway Source: MGI
    2. cell division Source: UniProtKB-KW
    3. cellular response to DNA damage stimulus Source: UniProtKB
    4. cellular response to organic substance Source: MGI
    5. endoplasmic reticulum unfolded protein response Source: MGI
    6. fat cell differentiation Source: MGI
    7. G1/S transition of mitotic cell cycle Source: UniProtKB
    8. lactation Source: MGI
    9. Leydig cell differentiation Source: Ensembl
    10. liver development Source: Ensembl
    11. mammary gland alveolus development Source: MGI
    12. mammary gland epithelial cell proliferation Source: MGI
    13. mitotic G1 DNA damage checkpoint Source: UniProtKB
    14. negative regulation of cell cycle arrest Source: UniProtKB
    15. negative regulation of epithelial cell differentiation Source: MGI
    16. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    17. negative regulation of Wnt signaling pathway Source: MGI
    18. organ regeneration Source: Ensembl
    19. positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
    20. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
    21. positive regulation of mammary gland epithelial cell proliferation Source: MGI
    22. positive regulation of protein phosphorylation Source: UniProtKB
    23. protein phosphorylation Source: MGI
    24. re-entry into mitotic cell cycle Source: MGI
    25. regulation of cell cycle Source: MGI
    26. regulation of G1/S transition of mitotic cell cycle Source: MGI
    27. response to calcium ion Source: Ensembl
    28. response to corticosterone Source: Ensembl
    29. response to drug Source: Ensembl
    30. response to estrogen Source: Ensembl
    31. response to ethanol Source: Ensembl
    32. response to iron ion Source: Ensembl
    33. response to magnesium ion Source: Ensembl
    34. response to organonitrogen compound Source: Ensembl
    35. response to UV-A Source: UniProtKB
    36. response to vitamin E Source: Ensembl
    37. response to X-ray Source: Ensembl
    38. transcription, DNA-templated Source: UniProtKB-KW
    39. Wnt signaling pathway Source: MGI

    Keywords - Molecular functioni

    Cyclin, Repressor

    Keywords - Biological processi

    Cell cycle, Cell division, Transcription, Transcription regulation

    Enzyme and pathway databases

    ReactomeiREACT_196520. Pre-NOTCH Transcription and Translation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    G1/S-specific cyclin-D1
    Gene namesi
    Name:Ccnd1
    Synonyms:Cyl-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:88313. Ccnd1.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm By similarity. Membrane By similarity
    Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members.

    GO - Cellular componenti

    1. cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
    2. cytoplasm Source: MGI
    3. cytosol Source: Reactome
    4. membrane Source: UniProtKB-SubCell
    5. nucleoplasm Source: Reactome
    6. nucleus Source: UniProtKB
    7. transcriptional repressor complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi269 – 2691K → R: Promotes location to the nucleus. Reduces proteasomal degradation, but does not prevent ubiquitination. 1 Publication
    Mutagenesisi286 – 2861T → A: Constitutively nuclear. Strongly reduced interaction with FBXO4. Strongly reduced ubiquitination. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 295295G1/S-specific cyclin-D1PRO_0000080431Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki269 – 269Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Modified residuei286 – 2861Phosphothreonine1 Publication

    Post-translational modificationi

    Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex By similarity.By similarity
    Ubiquitinated, primarily as 'Lys-48'-linked polyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation. Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner By similarity. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization.By similarity2 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP25322.
    PaxDbiP25322.
    PRIDEiP25322.

    PTM databases

    PhosphoSiteiP25322.

    Expressioni

    Gene expression databases

    ArrayExpressiP25322.
    BgeeiP25322.
    CleanExiMM_CCND1.
    GenevestigatoriP25322.

    Interactioni

    Subunit structurei

    Interacts with USP2. Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears independently of phosphorylation. Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity. Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression By similarity. Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Interacts directly with CDKN1B. Can form similar complexes with either CDKN1A or CDKN2A. Interacts with FBXO4.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Cdk4P3028513EBI-847243,EBI-847225
    Prmt5Q8CIG85EBI-847243,EBI-2527009

    Protein-protein interaction databases

    BioGridi198548. 16 interactions.
    DIPiDIP-284N.
    IntActiP25322. 18 interactions.
    MINTiMINT-1510765.

    Structurei

    3D structure databases

    ProteinModelPortaliP25322.
    SMRiP25322. Positions 22-267.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini28 – 152125Cyclin N-terminalAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi273 – 2808Glu-rich

    Sequence similaritiesi

    Belongs to the cyclin family. Cyclin D subfamily.Curated
    Contains 1 cyclin N-terminal domain.Curated

    Phylogenomic databases

    eggNOGiCOG5024.
    HOGENOMiHOG000008182.
    HOVERGENiHBG050837.
    InParanoidiP25322.
    KOiK04503.
    OMAiMKETVPL.
    OrthoDBiEOG7J447H.
    PhylomeDBiP25322.
    TreeFamiTF101004.

    Family and domain databases

    Gene3Di1.10.472.10. 2 hits.
    InterProiIPR013763. Cyclin-like.
    IPR014400. Cyclin_A/B/D/E/F.
    IPR004367. Cyclin_C-dom.
    IPR015451. Cyclin_D.
    IPR006671. Cyclin_N.
    [Graphical view]
    PANTHERiPTHR10177:SF67. PTHR10177:SF67. 1 hit.
    PfamiPF02984. Cyclin_C. 1 hit.
    PF00134. Cyclin_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001771. Cyclin_A_B_D_E. 1 hit.
    SMARTiSM00385. CYCLIN. 2 hits.
    [Graphical view]
    SUPFAMiSSF47954. SSF47954. 2 hits.
    PROSITEiPS00292. CYCLINS. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P25322-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEHQLLCCEV ETIRRAYPDT NLLNDRVLRA MLKTEETCAP SVSYFKCVQK    50
    EIVPSMRKIV ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPLKKSRLQ 100
    LLGATCMFVA SKMKETIPLT AEKLCIYTDN SIRPEELLQM ELLLVNKLKW 150
    NLAAMTPHDF IEHFLSKMPE ADENKQTIRK HAQTFVALCA TDVKFISNPP 200
    SMVAAGSVVA AMQGLNLGSP NNFLSCYRTT HFLSRVIKCD PDCLRACQEQ 250
    IEALLESSLR QAQQNVDPKA TEEEGEVEEE AGLACTPTDV RDVDI 295
    Length:295
    Mass (Da):33,429
    Last modified:May 1, 1992 - v1
    Checksum:i3A79736B4163251B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64403 mRNA. Translation: AAA37502.1.
    S78355 mRNA. Translation: AAB34495.1.
    BC044841 mRNA. Translation: AAH44841.1.
    CCDSiCCDS22055.1.
    PIRiA56523.
    RefSeqiNP_031657.1. NM_007631.2.
    UniGeneiMm.273049.

    Genome annotation databases

    EnsembliENSMUST00000093962; ENSMUSP00000091495; ENSMUSG00000070348.
    GeneIDi12443.
    KEGGimmu:12443.
    UCSCiuc009kqt.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64403 mRNA. Translation: AAA37502.1 .
    S78355 mRNA. Translation: AAB34495.1 .
    BC044841 mRNA. Translation: AAH44841.1 .
    CCDSi CCDS22055.1.
    PIRi A56523.
    RefSeqi NP_031657.1. NM_007631.2.
    UniGenei Mm.273049.

    3D structure databases

    ProteinModelPortali P25322.
    SMRi P25322. Positions 22-267.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198548. 16 interactions.
    DIPi DIP-284N.
    IntActi P25322. 18 interactions.
    MINTi MINT-1510765.

    Chemistry

    BindingDBi P25322.

    PTM databases

    PhosphoSitei P25322.

    Proteomic databases

    MaxQBi P25322.
    PaxDbi P25322.
    PRIDEi P25322.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000093962 ; ENSMUSP00000091495 ; ENSMUSG00000070348 .
    GeneIDi 12443.
    KEGGi mmu:12443.
    UCSCi uc009kqt.1. mouse.

    Organism-specific databases

    CTDi 595.
    MGIi MGI:88313. Ccnd1.

    Phylogenomic databases

    eggNOGi COG5024.
    HOGENOMi HOG000008182.
    HOVERGENi HBG050837.
    InParanoidi P25322.
    KOi K04503.
    OMAi MKETVPL.
    OrthoDBi EOG7J447H.
    PhylomeDBi P25322.
    TreeFami TF101004.

    Enzyme and pathway databases

    Reactomei REACT_196520. Pre-NOTCH Transcription and Translation.

    Miscellaneous databases

    NextBioi 281254.
    PROi P25322.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P25322.
    Bgeei P25322.
    CleanExi MM_CCND1.
    Genevestigatori P25322.

    Family and domain databases

    Gene3Di 1.10.472.10. 2 hits.
    InterProi IPR013763. Cyclin-like.
    IPR014400. Cyclin_A/B/D/E/F.
    IPR004367. Cyclin_C-dom.
    IPR015451. Cyclin_D.
    IPR006671. Cyclin_N.
    [Graphical view ]
    PANTHERi PTHR10177:SF67. PTHR10177:SF67. 1 hit.
    Pfami PF02984. Cyclin_C. 1 hit.
    PF00134. Cyclin_N. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001771. Cyclin_A_B_D_E. 1 hit.
    SMARTi SM00385. CYCLIN. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47954. SSF47954. 2 hits.
    PROSITEi PS00292. CYCLINS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle."
      Matsushime H., Roussel M.F., Ashmun R.A., Sherr C.J.
      Cell 65:701-713(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Genomic organization of the mouse cyclin D1 gene (Cyl-1)."
      Smith R., Peters G., Dickson C.
      Genomics 25:85-92(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "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].
      Strain: 129.
      Tissue: Mammary gland.
    4. "Redistribution of the CDK inhibitor p27 between different cyclin.CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation."
      Poon R.Y., Toyoshima H., Hunter T.
      Mol. Biol. Cell 6:1197-1213(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDKN1B IN THE CCND1-CDK4-CDKN1B COMPLEX.
    5. "Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex."
      Lin D.I., Barbash O., Kumar K.G., Weber J.D., Harper J.W., Klein-Szanto A.J., Rustgi A., Fuchs S.Y., Diehl J.A.
      Mol. Cell 24:355-366(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, INTERACTION WITH FBXO4, INTERACTION WITH A UBIQUITIN LIGASE COMPLEX CONTAINING CRYAB, SKP1, CUL1 AND FBXO4, MUTAGENESIS OF THR-286, PHOSPHORYLATION AT THR-286.
    6. "Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation."
      Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.
      Oncogene 28:4317-4325(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-269, INTERACTION WITH CDKN1B AND CDK4, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-269 AND THR-286.

    Entry informationi

    Entry nameiCCND1_MOUSE
    AccessioniPrimary (citable) accession number: P25322
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1992
    Last sequence update: May 1, 1992
    Last modified: October 1, 2014
    This is version 137 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3