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CCAR2 cell cycle and apoptosis regulator 2 [ Homo sapiens (human) ]

Gene ID: 57805, updated on 7-Apr-2024

Summary

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Official Symbol
CCAR2provided by HGNC
Official Full Name
cell cycle and apoptosis regulator 2provided by HGNC
Primary source
HGNC:HGNC:23360
See related
Ensembl:ENSG00000158941 MIM:607359; AllianceGenome:HGNC:23360
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
DBC1; DBC-1; NET35; p30DBC; p30 DBC; KIAA1967
Summary
Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including regulation of cellular protein metabolic process; regulation of signal transduction; and regulation of transcription, DNA-templated. Located in several cellular components, including mitochondrial matrix; nucleoplasm; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in testis (RPKM 30.7), brain (RPKM 20.0) and 25 other tissues See more
Orthologs
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Genomic context

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See CCAR2 in Genome Data Viewer
Location:
8p21.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (22604757..22621514)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (22878640..22895418)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (22462270..22479027)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22435755-22436448 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18995 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18997 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22439222-22439914 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22442189-22442858 Neighboring gene PDZ and LIM domain 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18998 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22447071-22448071 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22454615-22455362 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22455363-22456110 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18999 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19000 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19001 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22458799-22459676 Neighboring gene uncharacterized LOC107986876 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:22462104-22462604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27082 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19003 Neighboring gene chromosome 8 open reading frame 58 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22483969-22484602 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22485870-22486503 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:22486504-22487136 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22488646-22489180 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22489181-22489715 Neighboring gene bridging integrator 3 Neighboring gene BIN3 intronic transcript 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22515470-22516064 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:22516065-22516659 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:22526357-22526986 Neighboring gene CRISPRi-validated cis-regulatory element chr8.740 Neighboring gene uncharacterized LOC107986924 Neighboring gene early growth response 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Interaction of DBC1 with polyoma small T antigen promotes its degradation and negatively regulates tumorigenesis. Sarwar Z, et al. J Biol Chem, 2022 Feb. PMID 34921839, Free PMC Article
  2. DBC1 regulates Wnt/β-catenin-mediated expression of MACC1, a key regulator of cancer progression, in colon cancer. Kim HJ, et al. Cell Death Dis, 2018 Aug 6. PMID 30082743, Free PMC Article
  3. Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology. Magni M, et al. Mutat Res Rev Mutat Res, 2018 Apr-Jun. PMID 29807573
  4. Overexpression of DBC1, correlated with poor prognosis, is a potential therapeutic target for hepatocellular carcinoma. Li C, et al. Biochem Biophys Res Commun, 2017 Dec 16. PMID 29106957
  5. CCAR2 Is Required for Proliferation and Tumor Maintenance in Human Squamous Cell Carcinoma. Best SA, et al. J Invest Dermatol, 2017 Feb. PMID 27725203, Free PMC Article

See all (250) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.
    Title: SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.
  2. Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.
    Title: Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.
  3. Interaction of DBC1 with polyoma small T antigen promotes its degradation and negatively regulates tumorigenesis.
    Title: Interaction of DBC1 with polyoma small T antigen promotes its degradation and negatively regulates tumorigenesis.
  4. Distinct RNA polymerase transcripts direct the assembly of phase-separated DBC1 nuclear bodies in different cell lines.
    Title: Distinct RNA polymerase transcripts direct the assembly of phase-separated DBC1 nuclear bodies in different cell lines.
  5. Hydrogen sulfide-induced GAPDH sulfhydration disrupts the CCAR2-SIRT1 interaction to initiate autophagy.
    Title: Hydrogen sulfide-induced GAPDH sulfhydration disrupts the CCAR2-SIRT1 interaction to initiate autophagy.
  6. CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/beta-catenin-dependent transcriptional activation of SPARC.
    Title: CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/β-catenin-dependent transcriptional activation of SPARC.
  7. A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo.
    Title: A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo.
  8. Human cell cycle and apoptosis regulator 2 (DBC1) regulates transcriptional elongation factor ELL stability involving HDAC3, p300, and Siah1. DBC1 competes with histone deacetylase 3 (HDAC3) for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism.
    Title: DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes.
  9. Because DBC1 maintains p53 stability in the nucleus, where p53 exerts its tumor-suppressive transcriptional function, replacement of DBC1 functionality in DBC1-deleted tumors might enhance p53 function and chemosensitivity for therapeutic benefit.
    Title: DBC1 Regulates p53 Stability via Inhibition of CBP-Dependent p53 Polyubiquitination.
  10. DBC1 is required for LEF1/beta-catenin complex formation on the MACC1 enhancer and for long-distance enhancer-promoter interaction of the MACC1 locus. DBC1 overexpression further increased MACC1 expression in colonospheres and promoted sphere-forming abilities of colon cancer cells and drug resistance of colonospheres.
    Title: DBC1 regulates Wnt/β-catenin-mediated expression of MACC1, a key regulator of cancer progression, in colon cancer.
Submit: New GeneRIF Correction See all GeneRIFs (72)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association studies and heritability estimates of body mass index related phenotypes in bangladeshi adults.
EBI GWAS Catalog
Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease.
EBI GWAS Catalog
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance.
EBI GWAS Catalog
Risk alleles for multiple sclerosis identified by a genomewide study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pol gag-pol HIV-1 Pol is identified to have a physical interaction with KIAA1967 in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
Vif vif HIV-1 Vif interacts with CCAR2; predicted interaction to be relevant to gene regulation PubMed
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of cell cycle and apoptosis regulator 2 (CCAR2) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with KIAA1967 in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA1967

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables RNA polymerase II complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables adenyl-nucleotide exchange factor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables enzyme inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables enzyme inhibitor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables unfolded protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in DNA damage response IEA
Inferred from Electronic Annotation
more info
  
involved_in RNA splicing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in mRNA processing IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrial fragmentation involved in apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of catalytic activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA damage checkpoint IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of canonical Wnt signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of DNA-templated transcription elongation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of circadian rhythm ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of protein deacetylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of protein stability IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to UV IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in rhythmic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of DBIRD complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of chromatin IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in spindle IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
cell cycle and apoptosis regulator protein 2
Names
cell division cycle and apoptosis regulator protein 2
deleted in breast cancer 1

NCBI Reference Sequences (RefSeq)

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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_001363068.2 → NP_001349997.1  cell cycle and apoptosis regulator protein 2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC037459, AL137523, AL834351, BC065495, DA721640, DB240982
    UniProtKB/TrEMBL
    B3KTJ9
    Conserved Domains (2) summary
    pfam14443
    Location:343 → 451
    DBC1; DBC1
    pfam14444
    Location:60 → 112
    S1-like; S1-like

  2. NM_001363069.2 → NP_001349998.1  cell cycle and apoptosis regulator protein 2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC037459, AL137523, AL834351, BC065495, DA721640
    UniProtKB/TrEMBL
    B3KTJ9
    Conserved Domains (2) summary
    pfam14443
    Location:343 → 451
    DBC1; DBC1
    pfam14444
    Location:60 → 112
    S1-like; S1-like

  3. NM_001393997.1 → NP_001380926.1  cell cycle and apoptosis regulator protein 2 isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC037459
    Consensus CDS
    CCDS34863.1
    UniProtKB/Swiss-Prot
    A6NL03, B2RB79, D3DSR6, Q6P0Q9, Q8N163, Q8N3G7, Q8N8M1, Q8TF34, Q9H9Q9, Q9HD12, Q9NT55
    UniProtKB/TrEMBL
    B3KTJ9
    Related
    ENSP00000310670.4, ENST00000308511.9
    Conserved Domains (2) summary
    pfam14443
    Location:340 → 457
    DBC1
    pfam14444
    Location:55 → 112
    S1-like

  4. NM_021174.6 → NP_066997.3  cell cycle and apoptosis regulator protein 2 isoform 1

    See identical proteins and their annotated locations for NP_066997.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript, and encodes the longer isoform (1).
    Source sequence(s)
    AC037459, AL137523, AL834351, BC065495, DA110888
    Consensus CDS
    CCDS34863.1
    UniProtKB/Swiss-Prot
    A6NL03, B2RB79, D3DSR6, Q6P0Q9, Q8N163, Q8N3G7, Q8N8M1, Q8TF34, Q9H9Q9, Q9HD12, Q9NT55
    UniProtKB/TrEMBL
    B3KTJ9
    Related
    ENSP00000373930.3, ENST00000389279.7
    Conserved Domains (2) summary
    pfam14443
    Location:340 → 457
    DBC1
    pfam14444
    Location:55 → 112
    S1-like

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    22604757..22621514
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011544604.3 → XP_011542906.1  cell cycle and apoptosis regulator protein 2 isoform X1

    UniProtKB/TrEMBL
    B3KTJ9
    Conserved Domains (2) summary
    pfam14443
    Location:303 → 411
    DBC1; DBC1
    pfam14444
    Location:60 → 112
    S1-like; S1-like

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    22878640..22895418
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054360945.1 → XP_054216920.1  cell cycle and apoptosis regulator protein 2 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_199205.1: Suppressed sequence

    Description
    NM_199205.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8N163.2 GenPept UniProtKB/Swiss-Prot:Q8N163

Gene LinkOut

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