O08629 (TIF1B_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 100. History...
Names and origin
|Protein names||Recommended name:|
Transcription intermediary factor 1-beta
E3 SUMO-protein ligase TRIM28
KRAB-associated protein 1
Nuclear corepressor KAP-1
Tripartite motif-containing protein 28
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||835 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. 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 By similarity.
Oligomer; the RBCC domain homotrimerizes and interacts with one molecule of KRAB to form the KRAB-KAP1 corepressor complex By similarity. Binding to a KRAB domain is an absolute requirement for silencing gene expression By similarity. Interacts with CEBPB and NR3C1. 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 By similarity. Interacts with SMARCAD1. Interacts with, and sumoylates IRF7. Interacts with MAGEC2 By similarity. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 By similarity. Ref.3
Nucleus By similarity. Note: Associated with centromeric heterochromatin during cell differentiation through CBX1 By similarity.
The HP1 box is both necessary and sufficient for HP1 binding By similarity.
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 By similarity.
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 By similarity.
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 By similarity.
ATM-induced phosphorylation on Ser-825 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 By similarity.
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-555, Lys-780 and Lys-805 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-825 prevents sumoylation and allows de-repression of CDKN1A/p21 By similarity.
Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2 By similarity.
Belongs to the TRIM/RBCC family.
Contains 2 B box-type zinc fingers.
Contains 1 bromo domain.
Contains 1 PHD-type zinc finger.
Contains 1 RING-type zinc finger.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 835||835||Transcription intermediary factor 1-beta||PRO_0000056394|
|Domain||698 – 802||105||Bromo|
|Zinc finger||67 – 123||57||RING-type|
|Zinc finger||150 – 197||48||B box-type 1; atypical|
|Zinc finger||206 – 247||42||B box-type 2|
|Zinc finger||626 – 673||48||PHD-type|
|Region||248 – 378||131||Leucine zipper alpha helical coiled-coil region By similarity|
|Region||249 – 378||130||Interaction with MAGEC2 By similarity|
|Region||368 – 372||5||Involved in binding PPP1CA By similarity|
|Region||477 – 514||38||HP1 box|
|Motif||482 – 495||14||PxVxL motif|
|Compositional bias||2 – 60||59||Ala-rich|
|Compositional bias||55 – 58||4||Poly-Gly|
|Compositional bias||527 – 532||6||Poly-Ala|
Amino acid modifications
|Modified residue||24||1||Phosphoserine By similarity|
|Modified residue||52||1||Phosphoserine By similarity|
|Modified residue||306||1||N6-acetyllysine By similarity|
|Modified residue||342||1||N6-acetyllysine By similarity|
|Modified residue||379||1||N6-acetyllysine By similarity|
|Modified residue||441||1||Phosphoserine By similarity|
|Modified residue||472||1||Phosphoserine By similarity|
|Modified residue||474||1||Phosphoserine By similarity|
|Modified residue||480||1||Phosphoserine By similarity|
|Modified residue||490||1||Phosphoserine By similarity|
|Modified residue||502||1||Phosphoserine By similarity|
|Modified residue||595||1||Phosphoserine By similarity|
|Modified residue||684||1||Phosphoserine By similarity|
|Modified residue||698||1||Phosphoserine By similarity|
|Modified residue||753||1||Phosphoserine By similarity|
|Modified residue||758||1||Phosphoserine By similarity|
|Modified residue||771||1||N6-acetyllysine By similarity|
|Modified residue||775||1||N6-acetyllysine By similarity|
|Modified residue||825||1||Phosphoserine; by ATM and ATR and dsDNA kinase By similarity|
|Cross-link||555||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||677||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||751||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||780||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity|
|Cross-link||805||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity|
|Sequence conflict||220||1||V → A in AAB51518. Ref.2|
|Sequence conflict||263||1||K → R in AAB51518. Ref.2|
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||Emison E.S., Lewis B.C., Shim H., Li Q., Dang C.V., Lee L.A.|
Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 197-281.
|||"Sequence-specific transcriptional repression by KS1, a multiple-zinc-finger-Kruppel-associated box protein."|
Gebelein B., Urrutia R.
Mol. Cell. Biol. 21:928-939(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF382.
|+||Additional computationally mapped references.|
|BC166843 mRNA. Translation: AAI66843.1.|
U95041 mRNA. Translation: AAB51518.1.
|RefSeq||NP_446368.1. NM_053916.1. |
3D structure databases
|SMR||O08629. Positions 205-249, 625-813. |
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000029996; ENSRNOP00000031061; ENSRNOG00000027487. |
|UCSC||RGD:620289. rat. |
|RGD||620289. Trim28. |
Enzyme and pathway databases
Gene expression databases
|GermOnline||ENSRNOG00000027487. Rattus norvegicus. |
Family and domain databases
|Gene3D||1.20.920.10. 1 hit. |
22.214.171.124. 2 hits.
|InterPro||IPR003649. Bbox_C. |
|Pfam||PF00628. PHD. 1 hit. |
PF00643. zf-B_box. 2 hits.
|SMART||SM00502. BBC. 1 hit. |
SM00336. BBOX. 2 hits.
SM00297. BROMO. 1 hit.
SM00249. PHD. 1 hit.
SM00184. RING. 2 hits.
|SUPFAM||SSF57903. FYVE_PHD_ZnF. 1 hit. |
|PROSITE||PS00633. BROMODOMAIN_1. False negative. |
PS50014. BROMODOMAIN_2. False negative.
PS50119. ZF_BBOX. 2 hits.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
|Accession||Primary (citable) accession number: O08629|
Secondary accession number(s): B2RYN5
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|