TRIM28
UniProt ID: Q13263
Entrez ID: 10155
Protein name: Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28)
External links: UniprotKB HGNC RefSeq COSMIC
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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 re...
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 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. Also 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. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). 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 (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). 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 (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
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GO - Biological processes (BP):
chromatin organization [GO:0006325]; convergent extension involved in axis elongation [GO:0060028]; DNA methylation involved in embryo development [GO:0043045]; DNA repair [GO:0006281]; embryo implantation [GO:0007566]; embryonic placenta morphogenesis [GO:0060669]; epithelial to mesenchymal transit...
chromatin organization [GO:0006325]; convergent extension involved in axis elongation [GO:0060028]; DNA methylation involved in embryo development [GO:0043045]; DNA repair [GO:0006281]; embryo implantation [GO:0007566]; embryonic placenta morphogenesis [GO:0060669]; epithelial to mesenchymal transition [GO:0001837]; innate immune response [GO:0045087]; negative regulation of DNA demethylation [GO:1901536]; negative regulation of single stranded viral RNA replication via double stranded DNA intermediate [GO:0045869]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of DNA binding [GO:0043388]; positive regulation of DNA methylation-dependent heterochromatin assembly [GO:0090309]; positive regulation of DNA repair [GO:0045739]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of transcription, DNA-templated [GO:0045893]; protein autophosphorylation [GO:0046777]; protein sumoylation [GO:0016925]; Ras protein signal transduction [GO:0007265]; regulation of genetic imprinting [GO:2000653]; suppression of viral release by host [GO:0044790]
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GO - Molecular function (MF):
chromatin binding [GO:0003682]; chromo shadow domain binding [GO:0070087]; DNA binding [GO:0003677]; Krueppel-associated box domain binding [GO:0035851]; promoter-specific chromatin binding [GO:1990841]; protein kinase activity [GO:0004672]; RNA binding [GO:0003723]; SUMO transferase activity [GO:00...
chromatin binding [GO:0003682]; chromo shadow domain binding [GO:0070087]; DNA binding [GO:0003677]; Krueppel-associated box domain binding [GO:0035851]; promoter-specific chromatin binding [GO:1990841]; protein kinase activity [GO:0004672]; RNA binding [GO:0003723]; SUMO transferase activity [GO:0019789]; transcription coactivator activity [GO:0003713]; transcription corepressor activity [GO:0003714]; ubiquitin protein ligase binding [GO:0031625]; ubiquitin-protein transferase activity [GO:0004842]; zinc ion binding [GO:0008270]
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GO - Cellular component (CC):
chromatin [GO:0000785]; euchromatin [GO:0000791]; heterochromatin [GO:0000792]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; RNA polymerase II transcription regulator complex [GO:0090575]...
chromatin [GO:0000785]; euchromatin [GO:0000791]; heterochromatin [GO:0000792]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; RNA polymerase II transcription regulator complex [GO:0090575]
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TRIM28
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Kaplan plot for TRIM28 in
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*NOTE: the Kaplan plots were collected from OncoLnc