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    CCND2 cyclin D2 [ Homo sapiens ]

    Gene ID: 894, updated on 5-Feb-2012
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    Summary

    Official Symbol
    CCND2provided by HGNC
    Official Full Name
    cyclin D2provided by HGNC
    Primary source
    HGNC:1583
    See related
    Ensembl:ENSG00000118971; HPRD:00451; MIM:123833; Vega:OTTHUMG00000168123
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KIAK0002
    Summary
    The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. [provided by RefSeq, Oct 2008]
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    Genomic context

    Location :
    12p13
    Sequence :
    Chromosome: 12; NC_000012.11 (4382902..4414522)
    See CCND2 in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene heat shock 70kDa protein 8 pseudogene Neighboring gene ribosomal protein L18 pseudogene 9 Neighboring gene chromosome 12 open reading frame 5 Neighboring gene ribosomal protein S15 pseudogene 7 Neighboring gene fibroblast growth factor 23

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2. Yadav S, et al. J Biol Chem, 2011 Oct 28. PMID 21878650.
    2. Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma. Igawa T, et al. Cancer Sci, 2011 Nov. PMID 21790895.
    3. Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels. Salpeter SJ, et al. Endocrinology, 2011 Jul. PMID 21521747.
    4. CD5-positive, cyclinD1-negative mantle cell lymphoma with a translocation involving the CCND2 gene and the IGL locus. Shiller SM, et al. Cancer Genet, 2011 Mar. PMID 21504716.
    5. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. Shahi MH, et al. BMC Cancer, 2010 Nov 8. PMID 21059263.

    See all (103) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Cyclin D2 is overexpressed in the proliferation centers of CLL/SLL and this is due, in part, to the upregulation of NF-kappaB-related pathways.
      Title: Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma.
    2. ethanol-induced neuronal apoptosis follows both the mitochondria-mediated (miR-497- and BCL2-mediated) and non-mitochondria-mediated (miR-302b- and CCND2-mediated) pathway.
      Title: miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2.
    3. Major regulator of CCND2 expression in pancreatic beta cells is glucose acting via glycolysis and calcium channels; glucose up-regulates nuclear CCND2 in quiescent cells and down-regulates CCND2 in replicating cells.
      Title: Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels.
    4. High cyclin D2 is associated with higher grade (III and IV) of astrocytoma.
      Title: Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors.
    5. Authors present a CD5-positive, CCND1-negative B-cell lymphoma with a novel translocation involving CCND2 and the immunoglobulin lambda (IGL) gene.
      Title: CD5-positive, cyclinD1-negative mantle cell lymphoma with a translocation involving the CCND2 gene and the IGL locus.
    6. Valproic acid could down-regulate mRNA expression of cyclin D2 in the kasumi-1 leukemic cell line.
      Title: [Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion protein of kasumi-1 leukemic cell line].
    7. the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and let-7a down-regulated the expression of E2F2 and CCND2, suppressing prostate cancer cell proliferation in culture
      Title: MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2.
    8. sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 are differently regulated in medulloblastoma and astrocytoma
      Title: Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma.
    9. Our result supported the finding that ubiquitin-specific protease 22 can interact with cyclin D2 and active cyclin D2 activity.
      Title: Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer.
    10. hypermethylation in tumors from non-small cell lung cancer patients is associated with gender and histologic type
      Title: DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type.
    Submit: New GeneRIF Correction See all (51)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Genome-wide association study of hematological and biochemical traits in a Japanese population.

    Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts.

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NC_000012.9 NP_001697.2 BCL6    BIND  PubMed BCL6 interacts with the CCND2 promoter region. 
    NC_000012.9 NP_006302.2 NCOR1    BIND  PubMed NcoR interacts with the CCND2 promoter region. 
    NC_000012.9 NP_006303.1 NCOR2    BIND  PubMed SMRT interacts with the CCND2 promoter region. 
    NC_000012.9 NP_003143.2 STAT5A    BIND  PubMed STAT5A interacts with Cyclin D2 promoter. 
    NP_001750.1 NP_000066.1 CDK4    BIND  PubMed CCND2 interacts with CDK4 
    P30279 O43823 AKAP8    HPRD  PubMed  
    P30279 P11802 CDK4    HPRD  PubMed  
    P30279 Q00535 CDK5    HPRD  PubMed  
    P30279 Q00534 CDK6    HPRD  PubMed  
    P30279 P38936 CDKN1A    HPRD  PubMed  
    P30279 P46527 CDKN1B    HPRD  PubMed  
    P30279 Cyclin D binding myb like transcription factor 1 DMTF1    HPRD  PubMed  
    P30279 Q9NQX5 NPDC1    HPRD  PubMed  
    P30279 P35227 PCGF2    HPRD  PubMed  
    P30279 P06400 RB1    HPRD  PubMed  
    P30279 Q01196 RUNX1    HPRD  PubMed  
    BioGRID:107334 BioGRID:115561 AKAP8    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107334 BioGRID:107454 CDK4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107334 BioGRID:107455 CDK5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107334 BioGRID:107456 CDK6    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107334 BioGRID:107460 CDKN1A    BioGRID  PubMed Two-hybrid 
    BioGRID:107334 BioGRID:107461 CDKN1B    BioGRID  PubMed Two-hybrid 
    BioGRID:107334 BioGRID:107463 CDKN2A    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107334 BioGRID:121167 NPDC1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107334 BioGRID:115301 RBX1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107334 BioGRID:118987 SERTAD1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107334 BioGRID:113100 TSC2    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Cell cycle, organism-specific biosystem (from WikiPathways)
      Cell cycle, organism-specific biosystem(From http://en.wikipedia.org/wiki/Cell_cycle) The cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle in...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cyclin D associated events in G1, organism-specific biosystem (from REACTOME)
      Cyclin D associated events in G1, organism-specific biosystemThree D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and...
    • DNA damage response (only ATM dependent), organism-specific biosystem (from WikiPathways)
      DNA damage response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, organism-specific biosystem (from KEGG)
      Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, conserved biosystem (from KEGG)
      Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • G1 Phase, organism-specific biosystem (from REACTOME)
      G1 Phase, organism-specific biosystemEarly cell cycle progression in G1 is under the control of the D-type cyclins together with Cdk4 and Cdk6. An important target for these CDKs is the Retinoblastoma (Rb) protein, which when phosphoryl...
    • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
      G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • IL-7 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-7 Signaling Pathway, organism-specific biosystemInterleukin-7 belongs to a family of cytokines, which includes IL-2, IL-4, IL-9, IL-15 and IL-21. It signals through a receptor complex consisting of IL-7 receptor alpha chain (IL7RA) and a common ga...
    • IL2 signaling events mediated by STAT5, organism-specific biosystem (from Pathway Interaction Database)
      IL2 signaling events mediated by STAT5, organism-specific biosystem
      IL2 signaling events mediated by STAT5
    • Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
      Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
    • Jak-STAT signaling pathway, conserved biosystem (from KEGG)
      Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
    • Measles, organism-specific biosystem (from KEGG)
      Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Measles, conserved biosystem (from KEGG)
      Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Ovarian Infertility Genes, organism-specific biosystem (from WikiPathways)
      Ovarian Infertility Genes, organism-specific biosystemOvarian ???bottleneck??? genes associated with infertility. A valuable approach to the study of infertility is the comparison of mutations of individual human and mouse genes associated with infertil...
    • Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem
      Regulation of Wnt-mediated beta catenin signaling and target gene transcription
    • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
      Transcriptional misregulation in cancer, organism-specific biosystem
      Transcriptional misregulation in cancer
    • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
      Transcriptional misregulation in cancer, conserved biosystem
      Transcriptional misregulation in cancer
    • Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
      Validated targets of C-MYC transcriptional activation, organism-specific biosystem
      Validated targets of C-MYC transcriptional activation
    • Wnt Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell pluri...
    • Wnt signaling pathway, organism-specific biosystem (from KEGG)
      Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt signaling pathway, conserved biosystem (from KEGG)
      Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...

    Clone Names

    • MGC102758

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    cellular response to insulin stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    liver development IEA
    Inferred from Electronic Annotation
    more info
    		  
    ovarian follicle development IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of cyclin-dependent protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    regulation of neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to cAMP IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to estradiol stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to ethanol IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to organic cyclic compound IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to peptide hormone stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to testosterone stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    spermatogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cyclin-dependent protein kinase holoenzyme complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    G1/S-specific cyclin-D2
    Names
    G1/S-specific cyclin-D2
    G1/S-specific cyclin D2
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001759.3 → NP_001750.1  G1/S-specific cyclin-D2

      Status: VALIDATED

      Source sequence(s)
      AC006122, AI055922, BC089384, BX476896
      Consensus CDS
      CCDS8524.1
      UniProtKB/Swiss-Prot
      P30279
      Related
      ENSP00000261254, OTTHUMP00000237990, ENST00000261254, OTTHUMT00000398287
      Conserved Domains (2) summary
      cd00043
      Location:55 – 144
      Blast Score: 130
      CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...
      cl00050
      Location:154 – 266
      Blast Score: 184
      CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p5 Primary Assembly

      Range
      4382902..4414522
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      4239192..4271184
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC006122.24 (30883..62461) None
    genomic AF518005.1 AAM54041.1
    genomic CH471116.2 EAW88851.1
    genomic M88080.1 AAA51928.1
    genomic M88081.1 AAA51928.1
    genomic M88082.1 AAA51928.1
    genomic M88083.1 AAA51928.1
    mRNA AI055922.1 None
    mRNA AK223577.1 BAD97297.1
    mRNA AK291146.1 BAF83835.1
    mRNA BC010958.1 AAH10958.1
    mRNA BC014357.1 None
    mRNA BC089384.1 AAH89384.1
    mRNA BT019847.1 AAV38650.1
    mRNA BX476896.1 None
    mRNA BX647508.1 None
    mRNA D13639.1 BAA02802.1
    mRNA M90813.1 AAA51926.1
    mRNA X68452.1 CAA48493.1
    other-genetic DQ892845.2 ABM83771.1
    other-genetic DQ896091.2 ABM87090.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    P30279.1 GenPept UniProtKB/Swiss-Prot:P30279
    Q53ER2 GenPept UniProtKB/TrEMBL:Q53ER2
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content