Core component of the DBIRD complex, a multiprotein complexthat acts at the interface between core mRNP particles and RNApolymerase II (RNAPII) and integrates transcript elongation with theregulation of alternative splicing: the DBIRD complex affects localtranscript elongation rates and alternative splicing of a large set ofexons embedded in (A + T) -rich DNA regions. InhibitsSIRT1 deacetylase activity leading to increasing levels of p53/TP53acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferaseactivity. Mediates ligand-dependent transcriptionalactivation by nuclear hormone receptors. Plays acritical role in maintaining genomic stability and cellular integrityfollowing UV-induced genotoxic stress. Regulates thecircadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity ofNR1D1 through stabilization of NR1D1 protein levels by preventing itsubiquitination and subsequent degradation. Repressesthe ligand-dependent transcriptional activation function of ESR2. Acts as a regulator of PCK1 expression andgluconeogenesis by a mechanism that involves, at least in part, bothNR1D1 and SIRT1. Negatively regulates the deacetylaseactivity of HDAC3 and can alter its subcellular localization. Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediatedrepression of the beta-catenin pathway. Repressesligand-dependent transcriptional activation function of NR1H2 and NR1H3and inhibits the interaction of SIRT1 with NR1H3. Plays an important role in tumor suppression through p53/TP53regulation; stabilizes p53/TP53 by affecting its interaction withubiquitin ligase MDM2. Represses the transcriptionalactivator activity of BRCA1. Inhibits SIRT1 in aCHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 invitro. [1-6]

MSQFKRQRINPLPGGRNFSGTASTSLLGPPPGLLTPPVATELSQNARHLQGGEKQRVFTGIVTSLHDYFGVVDEEVFFQLSVVKGRLPQLGEKVLVKAAYNPGQAVPWNAVKVQTLSNQPLLKSPAPPLLHVAALGQKQGILGAQPQLIFQPHRIPPLFPQKPLSLFQTSHTLHLSHLNRFPARGPHGRLDQGRSDDYDSKKRKQRAGGEPWGAKKPRHDLPPYRVHLTPYTVDSPICDFLELQRRYRSLLVPSDFLSVHLSWLSAFPLSQPFSLHHPSRIQVSSEKEAAPDAGAEPITADSDPAYSSKVLLLSSPGLEELYRCCMLFVDDMAEPRETPEHPLKQIKFLLGRKEEEAVLVGGEWSPSLDGLDPQADPQVLVRTAIRCAQAQTGIDLSGCTKWWRFAEFQYLQPGPPRRLQTVVVYLPDVWTIMPTLEEWEALCQQKAAEAAPPTQEAQGETEPTEQAPDALEQAADTSRRNAETPEATTQQETDTDLPEAPPPPLEPAVIARPGCVNLSLHGIVEDRRPKERISFEVMVLAELFLEMLQRDFGYRVYKMLLSLPEKVVSPPEPEKEEAAKEEATKEEEAIKEEVVKEPKDEAQNEGPATESEAPLKEDGLLPKPLSSGGEEEEKPRGEASEDLCEMALDPELLLLRDDGEEEFAGAKLEDSEVRSVASNQSEMEFSSLQDMPKELDPSAVLPLDCLLAFVFFDANWCGYLHRRDLERILLTLGIRLSAEQAKQLVSRVVTQNICQYRSLQYSRQEGLDGGLPEEVLFGNLDLLPPPGKSTKPGAAPTEHKALVSHNGSLINVGSLLQRAEQQDSGRLYLENKIHTLELKLEESHNRFSATEVTNKTLAAEMQELRVRLAEAEETARTAERQKSQLQRLLQELRRRLTPLQLEIQRVVEKADSWVEKEEPAPSN