Homo sapiens Protein: CCND1
InnateDB Protein IDBP-61870.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CCND1
Protein Name cyclin D1
Synonyms BCL1; D11S287E; PRAD1; U21B31;
Species Homo sapiens
Ensembl Protein ENSP00000227507
InnateDB Gene IDBG-61868 (CCND1)
Protein Structure
UniProt Annotation
Function 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 G(1)/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 G(1) phase. Hypophosphorylates RB1 in early G(1) 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. {ECO:0000269PubMed:15241418, ECO:0000269PubMed:16569215, ECO:0000269PubMed:18417529, ECO:0000269PubMed:9106657}.
Subcellular Localization Nucleus {ECO:0000269PubMed:9106657}. Cytoplasm {ECO:0000269PubMed:9106657}. Membrane {ECO:0000269PubMed:9106657}. Note=Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members. {ECO:0000250}.
Disease Associations Note=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.Note=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) [MIM:254500]: A 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. {ECO:0000269PubMed:8695815}. Note=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.
Tissue Specificity
Number of Interactions This gene and/or its encoded proteins are associated with 164 experimentally validated interaction(s) in this database.
They are also associated with 36 interaction(s) predicted by orthology.
Experimentally validated
Total 164 [view]
Protein-Protein 129 [view]
Protein-DNA 29 [view]
Protein-RNA 3 [view]
DNA-DNA 3 [view]
Predicted by orthology
Total 36 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003714 transcription corepressor activity
GO:0004672 protein kinase activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0016301 kinase activity
GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0032403 protein complex binding
GO:0042826 histone deacetylase binding
GO:0070064 proline-rich region binding
Biological Process
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000278 mitotic cell cycle
GO:0000320 re-entry into mitotic cell cycle
GO:0001889 liver development
GO:0001934 positive regulation of protein phosphorylation
GO:0006351 transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006974 cellular response to DNA damage stimulus
GO:0007219 Notch signaling pathway
GO:0007595 lactation
GO:0008284 positive regulation of cell proliferation
GO:0010033 response to organic substance
GO:0010039 response to iron ion
GO:0010165 response to X-ray
GO:0010243 response to organonitrogen compound
GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
GO:0014070 response to organic cyclic compound
GO:0016055 Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030857 negative regulation of epithelial cell differentiation
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031100 organ regeneration
GO:0031571 mitotic G1 DNA damage checkpoint
GO:0032026 response to magnesium ion
GO:0033197 response to vitamin E
GO:0033327 Leydig cell differentiation
GO:0033598 mammary gland epithelial cell proliferation
GO:0033601 positive regulation of mammary gland epithelial cell proliferation
GO:0042493 response to drug
GO:0043627 response to estrogen
GO:0045444 fat cell differentiation
GO:0045471 response to ethanol
GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0048545 response to steroid hormone
GO:0051301 cell division
GO:0051384 response to glucocorticoid
GO:0051412 response to corticosterone
GO:0051592 response to calcium ion
GO:0051726 regulation of cell cycle
GO:0060070 canonical Wnt signaling pathway
GO:0060749 mammary gland alveolus development
GO:0070141 response to UV-A
GO:0071157 negative regulation of cell cycle arrest
GO:0071310 cellular response to organic substance
GO:2000045 regulation of G1/S transition of mitotic cell cycle
Cellular Component
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005923 tight junction
GO:0016020 membrane
GO:0017053 transcriptional repressor complex
Protein Structure and Domains
InterPro IPR004367 Cyclin, C-terminal domain
IPR006671 Cyclin, N-terminal
IPR013763 Cyclin-like
IPR014400 Cyclin A/B/D/E/F
PFAM PF02984
Post-translational Modifications
SwissProt P24385
PhosphoSite PhosphoSite-P24385
UniProt Splice Variant
Entrez Gene 595
UniGene Hs.732748
RefSeq NP_444284
OMIM 168461
HPRD 01346
EMBL AF511593 AK313136 AY830112 BC000076 BC001501 BC014078 BC023620 BC025302 BT019844 BT019845 CH471076 CR536538 CR542099 L09054 M64349 M73554 M74092 X59798 X77754 Z23022
GenPept AAA36481 AAA52136 AAA58392 AAH00076 AAH01501 AAH14078 AAH23620 AAH25302 AAM34300 AAV38647 AAV38648 AAV91344 BAG35955 CAA42470 CAA54800 CAA80558 CAG38775 CAG46896 EAW74748