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P25322

- CCND1_MOUSE

UniProt

P25322 - CCND1_MOUSE

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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

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 kinase activity Source: MGI
  4. protein kinase binding Source: UniProtKB
  5. 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
Complete GO annotation...

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-KW
  5. nucleoplasm Source: Reactome
  6. nucleus Source: UniProtKB
  7. transcriptional repressor complex Source: UniProtKB
Complete GO annotation...

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)1 Publication
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

BgeeiP25322.
CleanExiMM_CCND1.
ExpressionAtlasiP25322. baseline and differential.
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

        10         20         30         40         50
MEHQLLCCEV ETIRRAYPDT NLLNDRVLRA MLKTEETCAP SVSYFKCVQK
60 70 80 90 100
EIVPSMRKIV ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPLKKSRLQ
110 120 130 140 150
LLGATCMFVA SKMKETIPLT AEKLCIYTDN SIRPEELLQM ELLLVNKLKW
160 170 180 190 200
NLAAMTPHDF IEHFLSKMPE ADENKQTIRK HAQTFVALCA TDVKFISNPP
210 220 230 240 250
SMVAAGSVVA AMQGLNLGSP NNFLSCYRTT HFLSRVIKCD PDCLRACQEQ
260 270 280 290
IEALLESSLR QAQQNVDPKA TEEEGEVEEE AGLACTPTDV RDVDI
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

Bgeei P25322.
CleanExi MM_CCND1.
ExpressionAtlasi P25322. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 138 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