ID:TIF1B_HUMAN DESCRIPTION: RecName: Full=Transcription intermediary factor 1-beta; Short=TIF1-beta; AltName: Full=E3 SUMO-protein ligase TRIM28; EC=6.3.2.-; AltName: Full=KRAB-associated protein 1; Short=KAP-1; AltName: Full=KRAB-interacting protein 1; Short=KRIP-1; AltName: Full=Nuclear corepressor KAP-1; AltName: Full=RING finger protein 96; AltName: Full=Tripartite motif-containing protein 28; 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. PATHWAY: Protein modification; protein sumoylation. SUBUNIT: Oligomer; the RBCC domain homotrimerizes and interacts with one molecule of KRAB to form the KRAB-KAP1 corepressor complex. Binding to a KRAB domain is an absolute requirement for silencing gene expression. Interacts with CEBPB and NR3C1 (By similarity). Interacts with a number of KRAB-ZFP proteins including ZNF10, ZFP53, ZFP68, ZNF382 and ZNF256. Interacts with NCOR1, NR3C1 and CHD3. Interacts with CEBPB (via the RING-type and PHD-type zinc fingers). Component of a ternary complex that includes TRIM28, a HP1 protein (CBX1, CBX3 OR CBX5), a KRAB domain-containing protein, and DNA. Interacts with CBX5 (via the PxVxL motif); the interaction occurs in interphase nuclei and competes for binding POGZ. Interacts with POGZ; the interaction competes for interaction with CBX5. Interacts with SETDB1; the interaction is enhanced by KAP1 sumoylation, stimulates SETB1 histone methyltransferase activity and gene silencing. Interacts (via the PHD-type zinc finger) with UBE2I; the interaction is required for sumoylation and repressor activity. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor and DNA damage responses. Interacts directly with ERBB4; the interaction represses ERBB4-mediated transcription activity. Interacts with MDM2; the interaction contributes to p53/TP53 inactivation. Component of the TRIM28/KAP1-MDM2-p53/TP53; involved in regulating p53/TP53 stabilization and activity. Interacts (via the leucine zipper alpha helical coiled-coil) with E2F1 (central region); the interaction inhibits E2F1 acetylation and transcriptional activity. Interacts with PPP1CA; the interaction dephosphorylates TRIM28 at Ser-824 and forms a complex at the p21 promoter site. Interacts with PPP1CB; the interaction is weak but is increased on dephosphorylation at Ser-824. Interacts with FES/FPS. Interacts with SMARCAD1. Interacts with, and sumoylates IRF7. Interacts with MAGEC2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. INTERACTION: Q13185:CBX3; NbExp=3; IntAct=EBI-78139, EBI-78176; P23198:Cbx3 (xeno); NbExp=2; IntAct=EBI-78139, EBI-78162; P45973:CBX5; NbExp=7; IntAct=EBI-78139, EBI-78219; P43356:MAGEA2B; NbExp=6; IntAct=EBI-78139, EBI-5650739; P43357:MAGEA3; NbExp=3; IntAct=EBI-78139, EBI-5651459; P43360:MAGEA6; NbExp=2; IntAct=EBI-78139, EBI-1045155; Q9UBF1:MAGEC2; NbExp=14; IntAct=EBI-78139, EBI-5651487; Q9HCI5:MAGEE1; NbExp=2; IntAct=EBI-78139, EBI-949966; O75376:NCOR1; NbExp=4; IntAct=EBI-78139, EBI-347233; SUBCELLULAR LOCATION: Nucleus. Note=Associated with centromeric heterochromatin during cell differentiation through CBX1 (By similarity). TISSUE SPECIFICITY: Expressed in all tissues tested including spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. DOMAIN: The HP1 box is both necessary and sufficient for HP1 binding. DOMAIN: The PHD-type zinc finger enhances CEBPB transcriptional activity. The PHD-type zinc finger, the HP1 box and the bromo domain, function together to assemble the machinery required for repression of KRAB domain-containing proteins. Acts as an intramolecular SUMO E3 ligase for autosumoylation of bromodomain. DOMAIN: The RING-finger-B Box-coiled-coil/tripartite motif (RBCC/TRIM motif) is required for interaction with the KRAB domain of KRAB-zinc finger proteins. Binds four zinc ions per molecule. The RING finger and the N-terminal of the leucine zipper alpha helical coiled-coil region of RBCC are required for oligomerization. DOMAIN: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. ATM- induced phosphorylation on Ser-824 represses sumoylation leading to the de-repression of expression of a subset of genes involved in cell cycle control and apoptosis in response to genotoxic stress. Dephosphorylation by the phosphatases, PPP1CA and PP1CB forms, allows sumoylation and expression of TRIM28 target genes. PTM: Sumoylation/desumoylation events regulate TRIM28-mediated transcriptional repression. Sumoylation is required for interaction with CHD3 and SETDB1 and the corepressor activity. Represses and is repressed by Ser-824 phosphorylation. Enhances the TRIM28 corepressor activity, inhibiting transcriptional activity of a number of genes including GADD45A and CDKN1A/p21. Lys-554, Lys-779 and Lys-804 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-824 prevents sumoylation and allows de-repression of CDKN1A/p21. PTM: Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2. SIMILARITY: Belongs to the TRIM/RBCC family. SIMILARITY: Contains 2 B box-type zinc fingers. SIMILARITY: Contains 1 bromo domain. SIMILARITY: Contains 1 PHD-type zinc finger. SIMILARITY: Contains 1 RING-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13263
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0001105 RNA polymerase II transcription coactivator activity GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003713 transcription coactivator activity GO:0003714 transcription corepressor activity GO:0003723 RNA binding GO:0004672 protein kinase activity GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0008270 zinc ion binding GO:0016740 transferase activity GO:0031625 ubiquitin protein ligase binding GO:0035851 Krueppel-associated box domain binding GO:0043565 sequence-specific DNA binding GO:0046872 metal ion binding GO:0070087 chromo shadow domain binding GO:1990841 promoter-specific chromatin binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001701 in utero embryonic development GO:0001837 epithelial to mesenchymal transition GO:0006281 DNA repair GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0007265 Ras protein signal transduction GO:0007566 embryo implantation GO:0016567 protein ubiquitination GO:0016925 protein sumoylation GO:0042307 positive regulation of protein import into nucleus GO:0043045 DNA methylation involved in embryo development GO:0043388 positive regulation of DNA binding GO:0045087 innate immune response GO:0045739 positive regulation of DNA repair GO:0045869 negative regulation of single stranded viral RNA replication via double stranded DNA intermediate GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046777 protein autophosphorylation GO:0051259 protein oligomerization GO:0060028 convergent extension involved in axis elongation GO:0060669 embryonic placenta morphogenesis GO:0090309 positive regulation of methylation-dependent chromatin silencing GO:1901536 negative regulation of DNA demethylation GO:1902187 negative regulation of viral release from host cell GO:2000653 regulation of genetic imprinting
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
