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Protein

G1/S-specific cyclin-D1

Gene

CCND1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.4 Publications

GO - Molecular functioni

  • cyclin-dependent protein serine/threonine kinase regulator activity Source: Ensembl
  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • proline-rich region binding Source: UniProtKB
  • protein kinase activity Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cyclin, Repressor

Keywords - Biological processi

Cell cycle, Cell division, DNA damage, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110092-MONOMER.
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-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8849470. PTK6 Regulates Cell Cycle.
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

HGNCiHGNC:1582. CCND1.

Subcellular locationi

GO - Cellular componenti

  • bicellular tight junction Source: Ensembl
  • cyclin-dependent protein kinase holoenzyme complex Source: BHF-UCL
  • cytosol Source: Reactome
  • intracellular Source: LIFEdb
  • membrane Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • transcriptional repressor complex Source: UniProtKB
Complete GO annotation...

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.

PTM databases

iPTMnetiP24385.
PhosphoSitePlusiP24385.

Expressioni

Gene expression databases

BgeeiENSG00000110092.
CleanExiHS_CCND1.
ExpressionAtlasiP24385. baseline and differential.
GenevisibleiP24385. HS.

Organism-specific databases

HPAiCAB000024.
HPA027801.

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

WithEntry#Exp.IntActNotes
Q96TE03EBI-375001,EBI-10201595
BRCA1P383983EBI-375001,EBI-349905
CDK2P249413EBI-375001,EBI-375096
CDK4P1180222EBI-375001,EBI-295644
Cdk4P302852EBI-375001,EBI-847225From a different organism.
CDK6Q005344EBI-375001,EBI-295663
CDKN1AP3893615EBI-375001,EBI-375077
CDKN1BP465273EBI-375001,EBI-519280
Ralbp1Q627962EBI-375001,EBI-3956409From a different organism.
UHRF2Q96PU44EBI-375001,EBI-625304

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • proline-rich region binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107067. 94 interactors.
DIPiDIP-123N.
IntActiP24385. 52 interactors.
MINTiMINT-135422.
STRINGi9606.ENSP00000227507.

Chemistry databases

BindingDBiP24385.

Structurei

Secondary structure

1295
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 11Combined sources3
Helixi26 – 37Combined sources12
Helixi44 – 47Combined sources4
Helixi54 – 70Combined sources17
Helixi77 – 89Combined sources13
Turni96 – 98Combined sources3
Helixi99 – 114Combined sources16
Helixi121 – 127Combined sources7
Turni128 – 130Combined sources3
Helixi134 – 147Combined sources14
Turni148 – 150Combined sources3
Helixi157 – 166Combined sources10
Helixi172 – 190Combined sources19
Helixi194 – 197Combined sources4
Helixi200 – 218Combined sources19
Turni220 – 222Combined sources3
Helixi224 – 226Combined sources3
Helixi229 – 237Combined sources9
Helixi241 – 255Combined sources15
Turni256 – 260Combined sources5
Beta strandi261 – 263Combined sources3

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[»]
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
Contains 1 cyclin N-terminal domain.Curated

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR006671. Cyclin_N.
[Graphical view]
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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[»]
ProteinModelPortaliP24385.
SMRiP24385.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107067. 94 interactors.
DIPiDIP-123N.
IntActiP24385. 52 interactors.
MINTiMINT-135422.
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.

Protocols and materials databases

DNASUi595.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227507; ENSP00000227507; ENSG00000110092.
GeneIDi595.
KEGGihsa:595.

Organism-specific databases

CTDi595.
DisGeNETi595.
GeneCardsiCCND1.
HGNCiHGNC:1582. CCND1.
HPAiCAB000024.
HPA027801.
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.
OMAiMKETVPL.
OrthoDBiEOG091G0URX.
PhylomeDBiP24385.
TreeFamiTF101004.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110092-MONOMER.
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-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8849470. PTK6 Regulates Cell Cycle.
SignaLinkiP24385.
SIGNORiP24385.

Miscellaneous databases

ChiTaRSiCCND1. human.
EvolutionaryTraceiP24385.
GeneWikiiCyclin_D1.
GenomeRNAii595.
PROiP24385.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110092.
CleanExiHS_CCND1.
ExpressionAtlasiP24385. baseline and differential.
GenevisibleiP24385. HS.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR006671. Cyclin_N.
[Graphical view]
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCND1_HUMAN
AccessioniPrimary (citable) accession number: P24385
Secondary accession number(s): Q6LEF0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 30, 2016
This is version 187 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.