Nuclear corepressor for KRAB domain-containing zinc fingerproteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, asubunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me) ) to the promoter regions of KRAB target genes. Enhancestranscriptional repression by coordinating the increase in H3K9me, thedecrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac andH3K14ac, respectively) and the disposition of HP1 proteins to silencegene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in thetranscriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation andinhibiting E2F1 acetylation. May serve as a partial backup to preventE2F1-mediated apoptosis in the absence of RB1. Important regulator ofCDKN1A/p21 (CIP1). Has E3 SUMO-protein ligase activity toward itself viaits PHD-type zinc finger. Also specifically sumoylates IRF7, therebyinhibiting its transactivation activity. Ubiquitinates p53/TP53 leadingto its proteosomal degradation; the function is enhanced by MAGEC2 andMAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclearlocalization of KOX1, ZNF268 and ZNF300 transcription factors. Inassociation with isoform 2 of ZFP90, is required for thetranscriptional repressor activity of FOXP3 and the suppressivefunction of regulatory T-cells (Treg). Probably formsa corepressor complex required for activated KRAS-mediated promoterhypermethylation and transcriptional silencing of tumor suppressorgenes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionallyrepressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, isalso required for H3K9me3 and silencing of endogenous and introducedretroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leadingto their gene silencing. The SETDB1-TRIM28-ZNF274complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish ormaintain/protect H3K9me3 at these transcriptionally active regions. [1-2]

MAASAAAASAAAASAASGSPGPGEGSAGGEKRSTAPSAAASASASAAASSPAGGGAEALELLEHCGVCRERLRPEREPRLLPCLHSACSACLGPAAPAAANSSGDGGAAGDGTVVDCPVCKQQCFSKDIVENYFMRDSGSKAATDAQDANQCCTSCEDNAPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRSTGPAKSRDGERTVYCNVHKHEPLVLFCESCDTLTCRDCQLNAHKDHQYQFLEDAVRNQRKLLASLVKRLGDKHATLQKSTKEVRSSIRQVSDVQKRVQVDVKMAILQIMKELNKRGRVLVNDAQKVTEGQQERLERQHWTMTKIQKHQEHILRFASWALESDNNTALLLSKKLIYFQLHRALKMIVDPVEPHGEMKFQWDLNAWTKSAEAFGKIVAERPGTNSTGPAPMAPPRAPGPLSKQGSGSSQPMEVQEGYGFGSGDDPYSSAEPHVSGVKRSRSGEGEVSGLMRKVPRVSLERLDLDLTADSQPPVFKVFPGSTTEDYNLIVIERGAAAAATGQPGTAPAGTPGAPPLAGMAIVKEEETEAAIGAPPTATEGPETKPVLMALAEGPGAEGPRLASPSGSTSSGLEVVAPEGTSAPGGGPGTLDDSATICRVCQKPGDLVMCNQCEFCFHLDCHLPALQDVPGEEWSCSLCHVLPDLKEEDGSLSLDGADSTGVVAKLSPANQRKCERVLLALFCHEPCRPLHQLATDSTFSLDQPGGTLDLTLIRARLQEKLSPPYSSPQEFAQDVGRMFKQFNKLTEDKADVQSIIGLQRFFETRMNEAFGDTKFSAVLVEPPPMSLPGAGLSSQELSGGPGDGP