UniProtKB - P25322 (CCND1_MOUSE)
G1/S-specific cyclin-D1
Ccnd1
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 similarityGO - Molecular functioni
- cyclin-dependent protein serine/threonine kinase regulator activity Source: MGI
- enzyme binding Source: MGI
- histone deacetylase binding Source: MGI
- kinase activity Source: MGI
- proline-rich region binding Source: MGI
- protein-containing complex binding Source: MGI
- protein kinase activity Source: MGI
- protein kinase binding Source: UniProtKB
- transcription corepressor activity Source: UniProtKB
GO - Biological processi
- 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 cell cycle phase transition Source: GO_Central
- mitotic G1 DNA damage checkpoint signaling Source: UniProtKB
- negative regulation of epithelial cell differentiation Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of cell population proliferation Source: MGI
- positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
- positive regulation of G1/S transition of mitotic cell cycle Source: GO_Central
- 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 cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
- 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 xenobiotic stimulus Source: Ensembl
- response to X-ray Source: Ensembl
- Wnt signaling pathway Source: MGI
Keywordsi
Molecular function | Cyclin, Repressor |
Biological process | Cell cycle, Cell division, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-187577, SCF(Skp2)-mediated degradation of p27/p21 R-MMU-3214858, RMTs methylate histone arginines R-MMU-69231, Cyclin D associated events in G1 R-MMU-75815, Ubiquitin-dependent degradation of Cyclin D 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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:88313, Ccnd1 |
VEuPathDBi | HostDB:ENSMUSG00000070348 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
- Nucleus membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm 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.By similarity
Cytosol
- cytosol Source: Reactome
Nucleus
- nuclear membrane Source: UniProtKB-SubCell
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Other locations
- bicellular tight junction Source: MGI
- cyclin D1-CDK4 complex Source: ComplexPortal
- cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
- cytoplasm Source: MGI
- transcription repressor complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 269 | K → R: Promotes location to the nucleus. Reduces proteasomal degradation, but does not prevent ubiquitination. 1 Publication | 1 | |
Mutagenesisi | 286 | T → A: Constitutively nuclear. Strongly reduced interaction with FBXO4. Strongly reduced ubiquitination. 2 Publications | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080431 | 1 – 295 | G1/S-specific cyclin-D1Add BLAST | 295 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 269 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 286 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P25322 |
PeptideAtlasi | P25322 |
PRIDEi | P25322 |
ProteomicsDBi | 281250 |
PTM databases
iPTMneti | P25322 |
PhosphoSitePlusi | P25322 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000070348, Expressed in retina and 385 other tissues |
Genevisiblei | P25322, MM |
Interactioni
Subunit structurei
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 CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity (By similarity).
Interacts directly with CDKN1B (PubMed:8534916, PubMed:19767775). Can form similar complexes with either CDKN1A or CDKN2A (PubMed:8534916).
Interacts with FBXO4 (PubMed:17081987).
Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation.
Interacts with USP2.
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).
By similarity3 PublicationsBinary interactionsi
GO - Molecular functioni
- enzyme binding Source: MGI
- histone deacetylase binding Source: MGI
- proline-rich region binding Source: MGI
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 198548, 17 interactors |
ComplexPortali | CPX-2073, Cyclin D1-CDK4 complex CPX-2080, Cyclin D1-CDK6 complex |
CORUMi | P25322 |
DIPi | DIP-284N |
ELMi | P25322 |
IntActi | P25322, 22 interactors |
MINTi | P25322 |
STRINGi | 10090.ENSMUSP00000091495 |
Chemistry databases
BindingDBi | P25322 |
Miscellaneous databases
RNActi | P25322, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 28 – 152 | Cyclin N-terminalAdd BLAST | 125 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 262 – 283 | DisorderedSequence analysisAdd BLAST | 22 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0656, Eukaryota |
GeneTreei | ENSGT00940000157816 |
HOGENOMi | CLU_052190_0_0_1 |
InParanoidi | P25322 |
OMAi | SCYRTTH |
OrthoDBi | 1234739at2759 |
PhylomeDBi | P25322 |
TreeFami | TF101004 |
Family and domain databases
CDDi | cd00043, CYCLIN, 1 hit |
InterProi | View protein in InterPro IPR039361, Cyclin IPR013763, Cyclin-like IPR036915, Cyclin-like_sf IPR004367, Cyclin_C-dom IPR015451, Cyclin_D IPR006671, Cyclin_N |
PANTHERi | PTHR10177, PTHR10177, 1 hit PTHR10177:SF67, PTHR10177:SF67, 1 hit |
Pfami | View protein in Pfam PF02984, Cyclin_C, 1 hit PF00134, Cyclin_N, 1 hit |
SMARTi | View protein in SMART SM00385, CYCLIN, 2 hits SM01332, Cyclin_C, 1 hit |
SUPFAMi | SSF47954, SSF47954, 2 hits |
PROSITEi | View protein in PROSITE PS00292, CYCLINS, 1 hit |
i Sequence
Sequence statusi: Complete.
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
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 |
CCDSi | CCDS22055.1 |
PIRi | A56523 |
RefSeqi | NP_031657.1, NM_007631.2 |
Genome annotation databases
Ensembli | ENSMUST00000093962; ENSMUSP00000091495; ENSMUSG00000070348 |
GeneIDi | 12443 |
KEGGi | mmu:12443 |
UCSCi | uc009kqt.1, mouse |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS22055.1 |
PIRi | A56523 |
RefSeqi | NP_031657.1, NM_007631.2 |
3D structure databases
SMRi | P25322 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198548, 17 interactors |
ComplexPortali | CPX-2073, Cyclin D1-CDK4 complex CPX-2080, Cyclin D1-CDK6 complex |
CORUMi | P25322 |
DIPi | DIP-284N |
ELMi | P25322 |
IntActi | P25322, 22 interactors |
MINTi | P25322 |
STRINGi | 10090.ENSMUSP00000091495 |
Chemistry databases
BindingDBi | P25322 |
PTM databases
iPTMneti | P25322 |
PhosphoSitePlusi | P25322 |
Proteomic databases
PaxDbi | P25322 |
PeptideAtlasi | P25322 |
PRIDEi | P25322 |
ProteomicsDBi | 281250 |
Protocols and materials databases
Antibodypediai | 3660, 2045 antibodies from 53 providers |
DNASUi | 12443 |
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 |
VEuPathDBi | HostDB:ENSMUSG00000070348 |
Phylogenomic databases
eggNOGi | KOG0656, Eukaryota |
GeneTreei | ENSGT00940000157816 |
HOGENOMi | CLU_052190_0_0_1 |
InParanoidi | P25322 |
OMAi | SCYRTTH |
OrthoDBi | 1234739at2759 |
PhylomeDBi | P25322 |
TreeFami | TF101004 |
Enzyme and pathway databases
Reactomei | R-MMU-187577, SCF(Skp2)-mediated degradation of p27/p21 R-MMU-3214858, RMTs methylate histone arginines R-MMU-69231, Cyclin D associated events in G1 R-MMU-75815, Ubiquitin-dependent degradation of Cyclin D 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 |
Miscellaneous databases
BioGRID-ORCSi | 12443, 7 hits in 62 CRISPR screens |
ChiTaRSi | Ccnd1, mouse |
PROi | PR:P25322 |
RNActi | P25322, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000070348, Expressed in retina and 385 other tissues |
Genevisiblei | P25322, MM |
Family and domain databases
CDDi | cd00043, CYCLIN, 1 hit |
InterProi | View protein in InterPro IPR039361, Cyclin IPR013763, Cyclin-like IPR036915, Cyclin-like_sf IPR004367, Cyclin_C-dom IPR015451, Cyclin_D IPR006671, Cyclin_N |
PANTHERi | PTHR10177, PTHR10177, 1 hit PTHR10177:SF67, PTHR10177:SF67, 1 hit |
Pfami | View protein in Pfam PF02984, Cyclin_C, 1 hit PF00134, Cyclin_N, 1 hit |
SMARTi | View protein in SMART SM00385, CYCLIN, 2 hits SM01332, Cyclin_C, 1 hit |
SUPFAMi | SSF47954, SSF47954, 2 hits |
PROSITEi | View protein in PROSITE PS00292, CYCLINS, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CCND1_MOUSE | |
Accessioni | P25322Primary (citable) accession number: P25322 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 1992 |
Last sequence update: | May 1, 1992 | |
Last modified: | February 23, 2022 | |
This is version 195 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families