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MT001230

UniProt Annotations

Entry Information

Gene Name	cell cycle and apoptosis regulator 2
Protein Entry	CCAR2_HUMAN
UniProt ID	Q8N163
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q8N163-1; Sequence=Displayed; Name=2; IsoId=Q8N163-2; Sequence=VSP_017092; Note=No experimental confirmation available.;
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. {ECO:0000269\|PubMed:18235501, ECO:0000269\|PubMed:18235502, ECO:0000269\|PubMed:19131338, ECO:0000269\|PubMed:19218236, ECO:0000269\|PubMed:22446626, ECO:0000269\|PubMed:23352644, ECO:0000269\|PubMed:23398316}.
Interaction	P01106:MYC; NbExp=8; IntAct=EBI-355410, EBI-447544; Q9Q2G4:ORF (xeno); NbExp=5; IntAct=EBI-355410, EBI-6248094; Q96EB6:SIRT1; NbExp=9; IntAct=EBI-355410, EBI-1802965;
Ptm	Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity. {ECO:0000269\|PubMed:19608861, ECO:0000269\|PubMed:24126058}.
Ptm	ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage promotes binding to SIRT1. {ECO:0000269\|PubMed:17081983, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:19690332, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692, ECO:0000269\|PubMed:22735644}.
Sequence Caution	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};
Subcellular Location	Nucleus {ECO:0000269\|PubMed:23352644}. Note=Recruited to chromatin, post-UV irradiation.
Subunit	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, C11orf30/EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with NR1D1. {ECO:0000269\|PubMed:18235501, ECO:0000269\|PubMed:18235502, ECO:0000269\|PubMed:19131338, ECO:0000269\|PubMed:19218236, ECO:0000269\|PubMed:22446626, ECO:0000269\|PubMed:22735644, ECO:0000269\|PubMed:23352644, ECO:0000269\|PubMed:23398316, ECO:0000269\|PubMed:24126058}.
Tissue Specificity	Expressed ubiquitously in normal tissues. Expressed in 84 to 100% of neoplastic breast, lung, and colon tissues. {ECO:0000269\|PubMed:12370419}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/KIAA1967ID46056ch8p21.html";