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Protein

G1/S-specific cyclin-D1

Gene

Ccnd1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • canonical Wnt signaling pathway Source: MGI
  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to organic substance Source: MGI
  • endoplasmic reticulum unfolded protein response Source: MGI
  • fat cell differentiation Source: MGI
  • G1/S transition of mitotic cell cycle Source: MGI
  • lactation Source: MGI
  • Leydig cell differentiation Source: MGI
  • liver regeneration Source: MGI
  • mammary gland alveolus development Source: MGI
  • mammary gland epithelial cell proliferation Source: MGI
  • mitotic G1 DNA damage checkpoint Source: UniProtKB
  • negative regulation of cell cycle arrest Source: UniProtKB
  • negative regulation of epithelial cell differentiation Source: MGI
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of mammary gland epithelial cell proliferation Source: MGI
  • positive regulation of protein phosphorylation Source: UniProtKB
  • protein phosphorylation Source: MGI
  • re-entry into mitotic cell cycle Source: MGI
  • regulation of cell cycle Source: MGI
  • regulation of G1/S transition of mitotic cell cycle Source: MGI
  • response to calcium ion Source: Ensembl
  • response to corticosterone Source: Ensembl
  • response to estradiol Source: Ensembl
  • response to estrogen Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to iron ion Source: Ensembl
  • response to leptin Source: MGI
  • response to magnesium ion Source: Ensembl
  • response to organonitrogen compound Source: MGI
  • response to UV-A Source: UniProtKB
  • response to vitamin E Source: Ensembl
  • response to X-ray Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • Wnt signaling pathway Source: MGI

Keywordsi

Molecular functionCyclin, Repressor
Biological processCell cycle, Cell division, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-187577 SCF(Skp2)-mediated degradation of p27/p21
R-MMU-3214858 RMTs methylate histone arginines
R-MMU-69229 Ubiquitin-dependent degradation of Cyclin D1
R-MMU-69231 Cyclin D associated events in G1
R-MMU-8849470 PTK6 Regulates Cell Cycle
R-MMU-8878166 Transcriptional regulation by RUNX2
R-MMU-8934593 Regulation of RUNX1 Expression and Activity
R-MMU-8951936 RUNX3 regulates p14-ARF

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:88313 Ccnd1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi269K → R: Promotes location to the nucleus. Reduces proteasomal degradation, but does not prevent ubiquitination. 1 Publication1
Mutagenesisi286T → A: Constitutively nuclear. Strongly reduced interaction with FBXO4. Strongly reduced ubiquitination. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000804311 – 295G1/S-specific cyclin-D1Add BLAST295

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki269Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei286Phosphothreonine1 Publication1

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

PaxDbiP25322
PeptideAtlasiP25322
PRIDEiP25322

PTM databases

iPTMnetiP25322
PhosphoSitePlusiP25322

Expressioni

Gene expression databases

BgeeiENSMUSG00000070348
CleanExiMM_CCND1
ExpressionAtlasiP25322 baseline and differential
GenevisibleiP25322 MM

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198548, 14 interactors
ComplexPortaliCPX-2073 cyclin D1-CDK4 complex
CPX-2080 Cyclin D1-CDK6 complex
CORUMiP25322
DIPiDIP-284N
ELMiP25322
IntActiP25322, 22 interactors
MINTiP25322
STRINGi10090.ENSMUSP00000091495

Chemistry databases

BindingDBiP25322

Structurei

3D structure databases

ProteinModelPortaliP25322
SMRiP25322
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 152Cyclin N-terminalAdd BLAST125

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi273 – 280Glu-rich8

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00760000118939
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP25322
KOiK04503
OMAiLGSPNNF
OrthoDBiEOG091G0URX
PhylomeDBiP25322
TreeFamiTF101004

Family and domain databases

CDDicd00043 CYCLIN, 1 hit
InterProiView protein in InterPro
IPR039361 Cyclin
IPR013763 Cyclin-like
IPR036915 Cyclin-like_sf
IPR004367 Cyclin_C-dom
IPR015451 Cyclin_D
IPR006671 Cyclin_N
PANTHERiPTHR10177 PTHR10177, 1 hit
PTHR10177:SF67 PTHR10177:SF67, 1 hit
PfamiView protein in Pfam
PF02984 Cyclin_C, 1 hit
PF00134 Cyclin_N, 1 hit
SMARTiView protein in SMART
SM00385 CYCLIN, 2 hits
SM01332 Cyclin_C, 1 hit
SUPFAMiSSF47954 SSF47954, 2 hits
PROSITEiView protein in PROSITE
PS00292 CYCLINS, 1 hit

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:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Entry informationi

Entry nameiCCND1_MOUSE
AccessioniPrimary (citable) accession number: P25322
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: July 18, 2018
This is version 173 of the entry and version 1 of the sequence. See 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

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