CCAR2
entrez
57805
canonical
uniprot
Q8N163
canonical
ensembl
ENSG00000158941
resolver
ensp
ENSP00000310670
resolver
ensp
ENSP00000373930
resolver
ensp
ENSP00000580132
resolver
ensp
ENSP00000580137
resolver
genesymbol
CCAR2
resolver
genesymbol_syn
DBC1
resolver
genesymbol_syn
KIAA1967
resolver
hgnc
HGNC:23360
resolver
uniprot
A6NL03
resolver
uniprot
B2RB79
resolver
uniprot
D3DSR6
resolver
uniprot
Q6P0Q9
resolver
uniprot
Q8N3G7
resolver
uniprot
Q8N8M1
resolver
uniprot
Q8TF34
resolver
uniprot
Q9H9Q9
resolver
uniprot
Q9HD12
resolver
uniprot
Q9NT55
resolver
uniprot_entry
CCAR2_HUMAN
resolver
uniprot_sec
A6NL03
resolver
uniprot_sec
B2RB79
resolver
uniprot_sec
D3DSR6
resolver
uniprot_sec
Q6P0Q9
resolver
uniprot_sec
Q8N3G7
resolver
uniprot_sec
Q8N8M1
resolver
uniprot_sec
Q8TF34
resolver
uniprot_sec
Q9H9Q9
resolver
uniprot_sec
Q9HD12
resolver
uniprot_sec
Q9NT55
resolver
amino_acid_sequence
MSQFKRQRINPLPGGRNFSGTASTSLLGPPPGLLTPPVATELSQNARHLQGGEKQRVFTGIVTSLHDYFGVVDEEVFFQLSVVKGRLPQLGEKVLVKAAYNPGQAVPWNAVKVQTLSNQPLLKSPAPPLLHVAALGQKQGILGAQPQLIFQPHRIPPLFPQKPLSLFQTSHTLHLSHLNRFPARGPHGRLDQGRSDDYDSKKRKQRAGGEPWGAKKPRHDLPPYRVHLTPYTVDSPICDFLELQRRYRSLLVPSDFLSVHLSWLSAFPLSQPFSLHHPSRIQVSSEKEAAPDAGAEPITADSDPAYSSKVLLLSSPGLEELYRCCMLFVDDMAEPRETPEHPLKQIKFLLGRKEEEAVLVGGEWSPSLDGLDPQADPQVLVRTAIRCAQAQTGIDLSGCTKWWRFAEFQYLQPGPPRRLQTVVVYLPDVWTIMPTLEEWEALCQQKAAEAAPPTQEAQGETEPTEQAPDALEQAADTSRRNAETPEATTQQETDTDLPEAPPPPLEPAVIARPGCVNLSLHGIVEDRRPKERISFEVMVLAELFLEMLQRDFGYRVYKMLLSLPEKVVSPPEPEKEEAAKEEATKEEEAIKEEVVKEPKDEAQNEGPATESEAPLKEDGLLPKPLSSGGEEEEKPRGEASEDLCEMALDPELLLLRDDGEEEFAGAKLEDSEVRSVASNQSEMEFSSLQDMPKELDPSAVLPLDCLLAFVFFDANWCGYLHRRDLERILLTLGIRLSAEQAKQLVSRVVTQNICQYRSLQYSRQEGLDGGLPEEVLFGNLDLLPPPGKSTKPGAAPTEHKALVSHNGSLINVGSLLQRAEQQDSGRLYLENKIHTLELKLEESHNRFSATEVTNKTLAAEMQELRVRLAEAEETARTAERQKSQLQRLLQELRRRLTPLQLEIQRVVEKADSWVEKEEPAPSN
uniprot
proteins
function
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 (PubMed:22446626). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (PubMed:18235501, PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (PubMed:23398316). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (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). {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}.
uniprot
proteins
mass_dalton
102902
uniprot
proteins
mutagenesis
MUTAGEN 243..264; /note="Missing: Abolishes binding to SIRT1."; /evidence="ECO:0000269|PubMed:18235501"; MUTAGEN 454; /note="T->A: Significantly reduces association with SIRT1. Decreases sumoylation and the interaction of the sumoylated form with SIRT1. Inhibits CCAR2-PSIA3 interaction. Increases CCAR2-SENP1 interaction. Down-regulation of the signals related with the epithelial-mesenchymal transition of gastric cancer cells."; /evidence="ECO:0000269|PubMed:22735644, ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:25406032"; MUTAGEN 454; /note="T->D: Significantly increases association with SIRT1 and induces p53 acetylation and apoptosis. Increases sumoylation and the interaction of the sumoylated form with SIRT1. Promotes CCAR2-PSIA3 interaction. Decreases CCAR2-SENP1 interaction."; /evidence="ECO:0000269|PubMed:22735644, ECO:0000269|PubMed:25406032"; MUTAGEN 591; /note="K->R: Loss of sumoylation."; /evidence="ECO:0000269|PubMed:25406032"; MUTAGEN 667; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:25406032"; MUTAGEN 839; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:25406032
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:22735644, ECO:0000269|PubMed:25406032}.; PTM: Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity. {ECO:0000269|PubMed:24126058}.; PTM: 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. {ECO:0000269|PubMed:25406032}.
uniprot
proteins
pubmed
11853319
uniprot
proteins
pubmed
12370419
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18235501
uniprot
proteins
pubmed
18235502
uniprot
proteins
pubmed
18445686
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19131338
uniprot
proteins
pubmed
19218236
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20074560
uniprot
proteins
pubmed
20160719
uniprot
proteins
pubmed
21030595
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22446626
uniprot
proteins
pubmed
22735644
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23352644
uniprot
proteins
pubmed
23398316
uniprot
proteins
pubmed
23841676
uniprot
proteins
pubmed
24126058
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24273392
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24415752
uniprot
proteins
pubmed
24824780
uniprot
proteins
pubmed
24962073
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25361978
uniprot
proteins
pubmed
25406032
uniprot
proteins
pubmed
25661920
uniprot
proteins
pubmed
25732823
uniprot
proteins
pubmed
28112733
uniprot
proteins
sequence_length
923
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18445686, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:25661920}. Cytoplasm {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:24824780}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:18445686}. 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}.
uniprot
proteins