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

Summary

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: mouse all
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Genomic context

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_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.
Title: Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Risk alleles for multiple sclerosis identified by a genomewide study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH104266 (e-PCR)
- UniSTS:98591

RH102761 (e-PCR)
- UniSTS:97095

RH79699 (e-PCR)
- UniSTS:91211

MARC_17851-17852:1025010471:1 (e-PCR)
- UniSTS:268421

RH103685 (e-PCR)
- UniSTS:98010

STS-H96791 (e-PCR)
- UniSTS:26091

RH48987 (e-PCR)
- UniSTS:48629

RH103458 (e-PCR)
- UniSTS:97783

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	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)

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
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
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
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

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

22604757..22621514

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060932.1 Alternate T2T-CHM13v2.0

Range

22878640..22895418

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NM_199205.1: Suppressed sequence

Description

NM_199205.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.