InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CCND1

Summary

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

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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