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Protein

G1/S-specific cyclin-D1

Gene

CCND1

Organism
Homo sapiens (Human)
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.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-1912408 Pre-NOTCH Transcription and Translation
R-HSA-3214858 RMTs methylate histone arginines
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8849470 PTK6 Regulates Cell Cycle
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
R-HSA-8951430 RUNX3 regulates WNT signaling
R-HSA-8951936 RUNX3 regulates p14-ARF
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP24385
SIGNORiP24385

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D1
Alternative name(s):
B-cell lymphoma 1 protein
Short name:
BCL-1
BCL-1 oncogene
PRAD1 oncogene
Gene namesi
Name:CCND1
Synonyms:BCL1, PRAD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110092.3
HGNCiHGNC:1582 CCND1
MIMi168461 gene
neXtProtiNX_P24385

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

Involvement in diseasei

A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle.
A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer.
Multiple myeloma (MM)1 Publication
The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving CCND1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus.
Disease descriptionA malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia.
See also OMIM:254500

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi286T → A: Reduces ubiquitination and subsequent degradation by the proteasome; when associated with A-288. Abolishes ubiquitination and subsequent degradation following DNA damage. 2 Publications1
Mutagenesisi288T → A: Reduces ubiquitination and subsequent degradation by the proteasome; when associated with A-286. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi595
MalaCardsiCCND1
MIMi254500 phenotype
OpenTargetsiENSG00000110092
Orphaneti67038 B-cell chronic lymphocytic leukemia
52416 Mantle cell lymphoma
29073 Multiple myeloma
PharmGKBiPA75

Chemistry databases

ChEMBLiCHEMBL3610
DrugBankiDB01169 Arsenic trioxide

Polymorphism and mutation databases

BioMutaiCCND1
DMDMi116152

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000804301 – 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)By similarity
Modified residuei286PhosphothreonineCombined sources1 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.2 Publications
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 (By similarity). Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner. 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

EPDiP24385
PaxDbiP24385
PeptideAtlasiP24385
PRIDEiP24385
ProteomicsDBi54198

PTM databases

iPTMnetiP24385
PhosphoSitePlusiP24385

Expressioni

Gene expression databases

BgeeiENSG00000110092 Expressed in 219 organ(s), highest expression level in endometrium epithelium
CleanExiHS_CCND1
ExpressionAtlasiP24385 baseline and differential
GenevisibleiP24385 HS

Organism-specific databases

HPAiCAB000024
HPA027802

Interactioni

Subunit structurei

Interacts with FBXO4 (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 CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Interacts directly with CDKN1B. Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation. Can form similar complexes with either CDKN1A or CDKN2A. 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 similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107067, 100 interactors
ComplexPortaliCPX-2010 Cyclin D1-CDK4 complex
CPX-2014 Cyclin D1-CDK6 complex
CORUMiP24385
DIPiDIP-123N
IntActiP24385, 63 interactors
MINTiP24385
STRINGi9606.ENSP00000227507

Chemistry databases

BindingDBiP24385

Structurei

Secondary structure

1295
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP24385
SMRiP24385
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24385

Family & Domainsi

Domains and Repeats

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi272 – 280Poly-Glu9

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00760000118939
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP24385
KOiK04503
OMAiLGSPNNF
OrthoDBiEOG091G0URX
PhylomeDBiP24385
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, 1 hit
SM01332 Cyclin_C, 1 hit
SUPFAMiSSF47954 SSF47954, 2 hits
PROSITEiView protein in PROSITE
PS00292 CYCLINS, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

P24385-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEHQLLCCEV ETIRRAYPDA NLLNDRVLRA MLKAEETCAP SVSYFKCVQK
60 70 80 90 100
EVLPSMRKIV ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPVKKSRLQ
110 120 130 140 150
LLGATCMFVA SKMKETIPLT AEKLCIYTDN SIRPEELLQM ELLLVNKLKW
160 170 180 190 200
NLAAMTPHDF IEHFLSKMPE AEENKQIIRK HAQTFVALCA TDVKFISNPP
210 220 230 240 250
SMVAAGSVVA AVQGLNLRSP NNFLSYYRLT RFLSRVIKCD PDCLRACQEQ
260 270 280 290
IEALLESSLR QAQQNMDPKA AEEEEEEEEE VDLACTPTDV RDVDI
Length:295
Mass (Da):33,729
Last modified:March 1, 1992 - v1
Checksum:i3CC00C9905F58D3A
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H437F5H437_HUMAN
G1/S-specific cyclin-D1
CCND1
67Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130N → G in AAA52136 (PubMed:1827756).Curated1
Sequence conflicti168 – 169MP → IA in M74092 (PubMed:1833066).Curated2
Sequence conflicti188L → S in AAA52136 (PubMed:1827756).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59798 mRNA Translation: CAA42470.1
M74092 mRNA No translation available.
M64349 mRNA Translation: AAA52136.1
M73554 mRNA Translation: AAA58392.1
Z23022 mRNA Translation: CAA80558.1
BT019845 mRNA Translation: AAV38648.1
AF511593 Genomic DNA Translation: AAM34300.2
BC000076 mRNA Translation: AAH00076.1
BC001501 mRNA Translation: AAH01501.1
BC014078 mRNA Translation: AAH14078.1
BC023620 mRNA Translation: AAH23620.1
BC025302 mRNA Translation: AAH25302.1
L09054 Genomic DNA Translation: AAA36481.1
CCDSiCCDS8191.1
PIRiA38977
RefSeqiNP_444284.1, NM_053056.2
UniGeneiHs.523852

Genome annotation databases

EnsembliENST00000227507; ENSP00000227507; ENSG00000110092
GeneIDi595
KEGGihsa:595

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59798 mRNA Translation: CAA42470.1
M74092 mRNA No translation available.
M64349 mRNA Translation: AAA52136.1
M73554 mRNA Translation: AAA58392.1
Z23022 mRNA Translation: CAA80558.1
BT019845 mRNA Translation: AAV38648.1
AF511593 Genomic DNA Translation: AAM34300.2
BC000076 mRNA Translation: AAH00076.1
BC001501 mRNA Translation: AAH01501.1
BC014078 mRNA Translation: AAH14078.1
BC023620 mRNA Translation: AAH23620.1
BC025302 mRNA Translation: AAH25302.1
L09054 Genomic DNA Translation: AAA36481.1
CCDSiCCDS8191.1
PIRiA38977
RefSeqiNP_444284.1, NM_053056.2
UniGeneiHs.523852

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2W96X-ray2.30A1-271[»]
2W99X-ray2.80A1-271[»]
2W9FX-ray2.85A1-271[»]
2W9ZX-ray2.45A16-271[»]
5VZUX-ray2.70E/F279-295[»]
ProteinModelPortaliP24385
SMRiP24385
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107067, 100 interactors
ComplexPortaliCPX-2010 Cyclin D1-CDK4 complex
CPX-2014 Cyclin D1-CDK6 complex
CORUMiP24385
DIPiDIP-123N
IntActiP24385, 63 interactors
MINTiP24385
STRINGi9606.ENSP00000227507

Chemistry databases

BindingDBiP24385
ChEMBLiCHEMBL3610
DrugBankiDB01169 Arsenic trioxide

PTM databases

iPTMnetiP24385
PhosphoSitePlusiP24385

Polymorphism and mutation databases

BioMutaiCCND1
DMDMi116152

Proteomic databases

EPDiP24385
PaxDbiP24385
PeptideAtlasiP24385
PRIDEiP24385
ProteomicsDBi54198

Protocols and materials databases

DNASUi595
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227507; ENSP00000227507; ENSG00000110092
GeneIDi595
KEGGihsa:595

Organism-specific databases

CTDi595
DisGeNETi595
EuPathDBiHostDB:ENSG00000110092.3
GeneCardsiCCND1
HGNCiHGNC:1582 CCND1
HPAiCAB000024
HPA027802
MalaCardsiCCND1
MIMi168461 gene
254500 phenotype
neXtProtiNX_P24385
OpenTargetsiENSG00000110092
Orphaneti67038 B-cell chronic lymphocytic leukemia
52416 Mantle cell lymphoma
29073 Multiple myeloma
PharmGKBiPA75
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00760000118939
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP24385
KOiK04503
OMAiLGSPNNF
OrthoDBiEOG091G0URX
PhylomeDBiP24385
TreeFamiTF101004

Enzyme and pathway databases

ReactomeiR-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-1912408 Pre-NOTCH Transcription and Translation
R-HSA-3214858 RMTs methylate histone arginines
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8849470 PTK6 Regulates Cell Cycle
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
R-HSA-8951430 RUNX3 regulates WNT signaling
R-HSA-8951936 RUNX3 regulates p14-ARF
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP24385
SIGNORiP24385

Miscellaneous databases

ChiTaRSiCCND1 human
EvolutionaryTraceiP24385
GeneWikiiCyclin_D1
GenomeRNAii595
PROiPR:P24385
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110092 Expressed in 219 organ(s), highest expression level in endometrium epithelium
CleanExiHS_CCND1
ExpressionAtlasiP24385 baseline and differential
GenevisibleiP24385 HS

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, 1 hit
SM01332 Cyclin_C, 1 hit
SUPFAMiSSF47954 SSF47954, 2 hits
PROSITEiView protein in PROSITE
PS00292 CYCLINS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCCND1_HUMAN
AccessioniPrimary (citable) accession number: P24385
Secondary accession number(s): Q6LEF0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: September 12, 2018
This is version 204 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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