Protein: Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-A-interacting protein) (KRIP-1) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) (Q62318)
Organism: Mus musculus (Mouse)
Function: Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit 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. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568.
Subcellular location: Nucleus {ECO:0000269|PubMed:10330177, ECO:0000269|PubMed:11154279, ECO:0000269|PubMed:12154074, ECO:0000269|PubMed:22110054}. Note=Associated with centromeric heterochromatin during cell differentiation through CBX1 (PubMed:10330177). Localizes to sites of DNA damage (By similarity). {ECO:0000250|UniProtKB:Q13263, ECO:0000269|PubMed:10330177}.
Interaction partners:
- Histone-lysine N-methyltransferase SETDB1
- Chromobox protein homolog 5
- Zinc finger protein 809
- MAGE family member A3
- Zinc finger protein 57
- Chromobox protein homolog 3
- SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1
- Chromobox protein homolog 1
- DNA
- DNA helicase
Sequence:
MAASAAATAAASAATAASAASGSPGSGEGSAGGEKRPAASSAAAASAAASSPAGGGGEAQELLEHCGVCRERLRPERDPRLLPCLHSACSACLGPATPAAANNSGDGGSAGDGAMVDCPVCKQQCYSKDIVENYFMRDSGSKASSDSQDANQCCTSCEDNAPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRSTGPAKTRDGERTVYCNVHKHEPLVLFCESCDTLTCRDCQLNAHKDHQYQFLEDAVRNQRKLLASLVKRLGDKHATLQKNTKEVRSSIRQVSDVQKRVQVDVKMAILQIMKELNKRGRVLVNDAQKVTEGQQERLERQHWTMTKIQKHQEHILRFASWALESDNNTALLLSKKLIYFQLHRALKMIVDPVEPHGEMKFQWDLNAWTKSAEAFGKIVAERPGTNSTGPGPMAPPRAPGPLSKQGSGSSQPMEVQEGYGFGSDDPYSSAEPHVSGMKRSRSGEGEVSGLLRKVPRVSLERLDLDLTSDSQPPVFKVFPGSTTEDYNLIVIERGAAAAAAGQAGTVPPGAPGAPPLPGMAIVKEEETEAAIGAPPAAPEGPETKPVLMPLTEGPGAEGPRLASPSGSTSSGLEVVAPEVTSAPVSGPGILDDSATICRVCQKPGDLVMCNQCEFCFHLDCHLPALQDVPGEEWSCSLCHVLPDLKEEDGSLSLDGADSTGVVAKLSPANQRKCERVLLALFCHEPCRPLHQLATDSTFSMEQPGGTLDLTLIRARLQEKLSPPYSSPQEFAQDVGRMFKQFNKLTEDKADVQSIIGLQRFFETRMNDAFGDTKFSAVLVEPPPLNLPSAGLSSQELSGPGDGP