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Aliases for CCAR2 Gene

Aliases for CCAR2 Gene

  • Cell Cycle And Apoptosis Regulator 2 2 3 5
  • KIAA1967 2 3 4
  • Cell Division Cycle And Apoptosis Regulator Protein 2 3 4
  • P30 DBC 3 4
  • DBC-1 3 4
  • NET35 3 4
  • DBC1 3 4
  • Deleted In Breast Cancer Gene 1 Protein 4
  • DBIRD Complex Subunit KIAA1967 4
  • Deleted In Breast Cancer 1 3
  • Deleted In Breast Cancer 2
  • P30 DBC Protein 3
  • P30DBC 3
  • DBC.1 4

External Ids for CCAR2 Gene

Previous HGNC Symbols for CCAR2 Gene

  • KIAA1967

Previous GeneCards Identifiers for CCAR2 Gene

  • GC08P022463

Summaries for CCAR2 Gene

GeneCards Summary for CCAR2 Gene

CCAR2 (Cell Cycle And Apoptosis Regulator 2) is a Protein Coding gene. Diseases associated with CCAR2 include Estrogen-Receptor Negative Breast Cancer. Among its related pathways are Cellular response to heat stress and TNF-alpha/NF-kB Signaling Pathway. GO annotations related to this gene include poly(A) RNA binding and enzyme inhibitor activity. An important paralog of this gene is CCAR1.

UniProtKB/Swiss-Prot for CCAR2 Gene

  • Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3-specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:18235501, PubMed:18235502, PubMed:19131338, PubMed:19218236, PubMed:22446626, PubMed:23352644, PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978).

Gene Wiki entry for CCAR2 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CCAR2 Gene

Genomics for CCAR2 Gene

Regulatory Elements for CCAR2 Gene

Enhancers for CCAR2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around CCAR2 on UCSC Golden Path with GeneCards custom track

Promoters for CCAR2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around CCAR2 on UCSC Golden Path with GeneCards custom track

Genomic Location for CCAR2 Gene

Chromosome:
8
Start:
22,604,632 bp from pter
End:
22,621,514 bp from pter
Size:
16,883 bases
Orientation:
Plus strand

Genomic View for CCAR2 Gene

Genes around CCAR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCAR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCAR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCAR2 Gene

Proteins for CCAR2 Gene

  • Protein details for CCAR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N163-CCAR2_HUMAN
    Recommended name:
    Cell cycle and apoptosis regulator protein 2
    Protein Accession:
    Q8N163
    Secondary Accessions:
    • A6NL03
    • B2RB79
    • D3DSR6
    • Q6P0Q9
    • Q8N3G7
    • Q8N8M1
    • Q8TF34
    • Q9H9Q9
    • Q9HD12
    • Q9NT55

    Protein attributes for CCAR2 Gene

    Size:
    923 amino acids
    Molecular mass:
    102902 Da
    Quaternary structure:
    • Component of the DBIRD complex. Interacts with ZNF326/ZIRD; the interaction is direct. Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation of substrates. Interacts (via N-terminus) with SUV39H1; this interaction abolishes the interaction with SIRT1. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with NR1D1. Interacts (via N-terminus) with ESR1 and ESR2. Interacts (via N-terminus) with HDAC3 (via C-terminus). Interacts with HDAC1 and MED2F. Interacts with MCC. Interacts (via N-terminus) with NR1H2 and NR1H3 in a ligand-independent manner. Interacts with CSNK2A1. Interacts (via N-terminus) with p53/TP53. Interacts (via N-terminus) with BRCA1 (via the BRCT domains). Interacts (via N-terminus) with CHEK2 (via protein kinase domain). Interacts with PSEM3. Interacts (via N-terminus) with PSIA3 and SENP1. The sumoylated form shows a preferential interaction with SIRT1 as compared to its unmodified form.
    SequenceCaution:
    • Sequence=AAG02472.1; Type=Frameshift; Positions=610, 622, 794, 810; Evidence={ECO:0000305}; Sequence=BAB85553.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for CCAR2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCAR2 Gene

Proteomics data for CCAR2 Gene at MOPED

Post-translational modifications for CCAR2 Gene

  • Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity.
  • ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage promotes binding to SIRT1. Phosphorylation at Thr-454 promotes its sumoylation by switching the binding partner of CCAR2 from SENP1 to PIAS3.
  • Genotoxic stress induces its sumoylation and sumoylation promotes the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated deacetylation of p53/TP53. Sumoylation leads to transcriptional activation of p53/TP53 by sequestering SIRT1 from p53/TP53. Desumoylated by SENP1.
  • Ubiquitination at Lys 93, Lys 97, Lys 112, Lys 309, Lys 347, Lys 742, Lys 832, and Lys 839
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCAR2 Gene

Domains & Families for CCAR2 Gene

Protein Domains for CCAR2 Gene

Suggested Antigen Peptide Sequences for CCAR2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with CCAR2: view

No data available for Gene Families and UniProtKB/Swiss-Prot for CCAR2 Gene

Function for CCAR2 Gene

Molecular function for CCAR2 Gene

UniProtKB/Swiss-Prot Function:
Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3-specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:18235501, PubMed:18235502, PubMed:19131338, PubMed:19218236, PubMed:22446626, PubMed:23352644, PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978).

Gene Ontology (GO) - Molecular Function for CCAR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 17314511
genes like me logo Genes that share ontologies with CCAR2: view
genes like me logo Genes that share phenotypes with CCAR2: view

Animal Model Products

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CCAR2 Gene

Localization for CCAR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCAR2 Gene

Nucleus. Cytoplasm. Note=Recruited to chromatin, post-UV irradiation. Sequestered to the cytoplasm in the presence of MCC. Translocated to the cytoplasm during UV-induced apoptosis. {ECO:0000269 PubMed:20160719, ECO:0000269 PubMed:24824780}.

Gene Ontology (GO) - Cellular Components for CCAR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 15824730
genes like me logo Genes that share ontologies with CCAR2: view

No data available for Subcellular locations from COMPARTMENTS for CCAR2 Gene

Pathways & Interactions for CCAR2 Gene

genes like me logo Genes that share pathways with CCAR2: view

Pathways by source for CCAR2 Gene

Gene Ontology (GO) - Biological Process for CCAR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006397 mRNA processing IEA --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0008380 RNA splicing IEA,IMP 22446626
GO:0009411 response to UV IMP 23352644
genes like me logo Genes that share ontologies with CCAR2: view

No data available for SIGNOR curated interactions for CCAR2 Gene

Drugs & Compounds for CCAR2 Gene

No Compound Related Data Available

Transcripts for CCAR2 Gene

Alternative Splicing Database (ASD) splice patterns (SP) for CCAR2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21
SP1: - -
SP2:
SP3: -
SP4:
SP5: -
SP6:

Relevant External Links for CCAR2 Gene

GeneLoc Exon Structure for
CCAR2
ECgene alternative splicing isoforms for
CCAR2

Expression for CCAR2 Gene

mRNA expression in normal human tissues for CCAR2 Gene

Protein differential expression in normal tissues from HIPED for CCAR2 Gene

This gene is overexpressed in Tlymphocyte (12.2) and Lymph node (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for CCAR2 Gene



mRNA Expression by UniProt/SwissProt for CCAR2 Gene

Q8N163-CCAR2_HUMAN
Tissue specificity: Expressed in gastric carcinoma tissue and the expression gradually increases with the progression of the carcinoma (at protein level). Expressed ubiquitously in normal tissues. Expressed in 84 to 100% of neoplastic breast, lung, and colon tissues.
genes like me logo Genes that share expression patterns with CCAR2: view

Protein tissue co-expression partners for CCAR2 Gene

- Elite partner

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for CCAR2 Gene

Orthologs for CCAR2 Gene

This gene was present in the common ancestor of animals.

Orthologs for CCAR2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia KIAA1967 35
  • 87.95 (n)
  • 88.76 (a)
CCAR2 36
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia KIAA1967 35
  • 90.05 (n)
  • 93.46 (a)
CCAR2 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ccar2 35
  • 87.92 (n)
  • 91.54 (a)
Ccar2 16
Ccar2 36
  • 91 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia KIAA1967 35
  • 99.49 (n)
  • 99.67 (a)
CCAR2 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ccar2 35
  • 87.89 (n)
  • 91.43 (a)
oppossum
(Monodelphis domestica)
Mammalia CCAR2 36
  • 73 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CCAR2 36
  • 63 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CCAR2 36
  • 58 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii CCAR2 36
  • 29 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea lst-3 36
  • 17 (a)
OneToMany
Species with no ortholog for CCAR2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for CCAR2 Gene

ENSEMBL:
Gene Tree for CCAR2 (if available)
TreeFam:
Gene Tree for CCAR2 (if available)

Paralogs for CCAR2 Gene

Paralogs for CCAR2 Gene

(1) SIMAP similar genes for CCAR2 Gene using alignment to 9 proteins:

genes like me logo Genes that share paralogs with CCAR2: view

Variants for CCAR2 Gene

Sequence variations from dbSNP and Humsavar for CCAR2 Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type
rs2291230 -- 22,606,184(+) AGGTT(C/G)GGCAT intron-variant
rs2291231 -- 22,606,399(+) AATCC(C/T)AGAAG intron-variant
rs2291232 -- 22,606,551(+) CAGAG(C/T)GTGAT intron-variant
rs2291233 -- 22,606,807(+) TTGTG(C/T)AAGGT intron-variant
rs2291234 -- 22,606,877(+) CCTCT(C/T)CTGAT intron-variant

Variation tolerance for CCAR2 Gene

Residual Variation Intolerance Score: 6.48% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.82; 47.76% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CCAR2 Gene

Human Gene Mutation Database (HGMD)
CCAR2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for CCAR2 Gene

Disorders for CCAR2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for CCAR2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
estrogen-receptor negative breast cancer
- elite association - COSMIC cancer census association via MalaCards
Search CCAR2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for CCAR2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CCAR2
genes like me logo Genes that share disorders with CCAR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CCAR2 Gene

Publications for CCAR2 Gene

  1. DBC2, a candidate for a tumor suppressor gene involved in breast cancer. (PMID: 12370419) Hamaguchi M. … Wigler M.H. (Proc. Natl. Acad. Sci. U.S.A. 2002) 2 3 4 67
  2. Repression of estrogen receptor beta function by putative tumor suppressor DBC1. (PMID: 20074560) Koyama S. … Taketani Y. (Biochem. Biophys. Res. Commun. 2010) 3 23
  3. Identification of DBC1 as a transcriptional repressor for BRCA1. (PMID: 20160719) Hiraike H. … Taketani Y. (Br. J. Cancer 2010) 3 23
  4. Modulation of estrogen receptor alpha protein level and survival function by DBC-1. (PMID: 17473282) Trauernicht A.M. … Boyer T.G. (Mol. Endocrinol. 2007) 3 23
  5. MCC inhibits beta-catenin transcriptional activity by sequestering DBC1 in the cytoplasm. (PMID: 24824780) Pangon L. … Kohonen-Corish M.R. (Int. J. Cancer 2015) 3

Products for CCAR2 Gene

Sources for CCAR2 Gene

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