Search Results

Overview

Uniprot IDQ8N163
Protein NameCell cycle and apoptosis regulator protein 2
Gene NameCCAR2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
215 GGEPWGAKKPRHDLP
216 GEPWGAKKPRHDLPP

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)

Protein Sequence

10 MSQFKRQRIN 20 PLPGGRNFSG 30 TASTSLLGPP 40 PGLLTPPVAT 50 ELSQNARHLQ 60 GGEKQRVFTG 70 IVTSLHDYFG 80 VVDEEVFFQL 90 SVVKGRLPQL 100 GEKVLVKAAY 110 NPGQAVPWNA 120 VKVQTLSNQP 130 LLKSPAPPLL 140 HVAALGQKQG 150 ILGAQPQLIF 160 QPHRIPPLFP 170 QKPLSLFQTS 180 HTLHLSHLNR 190 FPARGPHGRL 200 DQGRSDDYDS 210 KKRKQRAGGE 220 PWGAKKPRHD 230 LPPYRVHLTP 240 YTVDSPICDF 250 LELQRRYRSL 260 LVPSDFLSVH 270 LSWLSAFPLS 280 QPFSLHHPSR 290 IQVSSEKEAA 300 PDAGAEPITA 310 DSDPAYSSKV 320 LLLSSPGLEE 330 LYRCCMLFVD 340 DMAEPRETPE 350 HPLKQIKFLL 360 GRKEEEAVLV 370 GGEWSPSLDG 380 LDPQADPQVL 390 VRTAIRCAQA 400 QTGIDLSGCT 410 KWWRFAEFQY 420 LQPGPPRRLQ 430 TVVVYLPDVW 440 TIMPTLEEWE 450 ALCQQKAAEA 460 APPTQEAQGE 470 TEPTEQAPDA 480 LEQAADTSRR 490 NAETPEATTQ 500 QETDTDLPEA 510 PPPPLEPAVI 520 ARPGCVNLSL 530 HGIVEDRRPK 540 ERISFEVMVL 550 AELFLEMLQR 560 DFGYRVYKML 570 LSLPEKVVSP 580 PEPEKEEAAK 590 EEATKEEEAI 600 KEEVVKEPKD 610 EAQNEGPATE 620 SEAPLKEDGL 630 LPKPLSSGGE 640 EEEKPRGEAS 650 EDLCEMALDP 660 ELLLLRDDGE 670 EEFAGAKLED 680 SEVRSVASNQ 690 SEMEFSSLQD 700 MPKELDPSAV 710 LPLDCLLAFV 720 FFDANWCGYL 730 HRRDLERILL 740 TLGIRLSAEQ 750 AKQLVSRVVT 760 QNICQYRSLQ 770 YSRQEGLDGG 780 LPEEVLFGNL 790 DLLPPPGKST 800 KPGAAPTEHK 810 ALVSHNGSLI 820 NVGSLLQRAE 830 QQDSGRLYLE 840 NKIHTLELKL 850 EESHNRFSAT 860 EVTNKTLAAE 870 MQELRVRLAE 880 AEETARTAER 890 QKSQLQRLLQ 900 ELRRRLTPLQ 910 LEIQRVVEKA 920 DSWVEKEEPA PSN

Gene Ontology

Classification GO ID Description
Biological Process GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0044609 DBIRD complex
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005819 spindle
Molecular Function GO:0000774 adenyl-nucleotide exchange factor activity
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0004857 enzyme inhibitor activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0000993 RNA polymerase II complex binding
Molecular Function GO:0051082 unfolded protein binding
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0043653 mitochondrial fragmentation involved in apoptotic process
Biological Process GO:0006397 mRNA processing
Biological Process GO:0043086 negative regulation of catalytic activity
Biological Process GO:0030308 negative regulation of cell growth
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Biological Process GO:0043065 positive regulation of apoptotic process
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:2000003 positive regulation of DNA damage checkpoint
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0032784 regulation of DNA-templated transcription elongation
Biological Process GO:0090311 regulation of protein deacetylation
Biological Process GO:0031647 regulation of protein stability
Biological Process GO:0043484 regulation of RNA splicing
Biological Process GO:0009411 response to UV
Biological Process GO:0048511 rhythmic process
Biological Process GO:0008380 RNA splicing
Biological Process GO:0016055 Wnt signaling pathway

Reference

[1] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.