Trim28
entrez
21849
canonical
uniprot
Q62318
canonical
ensembl
ENSMUSG00000005566
resolver
ensp
ENSMUSP00000005705
resolver
genesymbol
Trim28
resolver
genesymbol_syn
Kap1
resolver
genesymbol_syn
Krip1
resolver
genesymbol_syn
Tif1b
resolver
uniprot
P70391
resolver
uniprot
Q5EBP9
resolver
uniprot
Q8C283
resolver
uniprot
Q99PN4
resolver
uniprot_entry
Q5EBP9_MOUSE
resolver
uniprot_entry
TIF1B_MOUSE
resolver
uniprot_sec
P70391
resolver
uniprot_sec
Q8C283
resolver
uniprot_sec
Q99PN4
resolver
amino_acid_sequence
MAASAAATAAASAATAASAASGSPGSGEGSAGGEKRPAASSAAAASAAASSPAGGGGEAQELLEHCGVCRERLRPERDPRLLPCLHSACSACLGPATPAAANNSGDGGSAGDGAMVDCPVCKQQCYSKDIVENYFMRDSGSKASSDSQDANQCCTSCEDNAPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRSTGPAKTRDGERTVYCNVHKHEPLVLFCESCDTLTCRDCQLNAHKDHQYQFLEDAVRNQRKLLASLVKRLGDKHATLQKNTKEVRSSIRQVSDVQKRVQVDVKMAILQIMKELNKRGRVLVNDAQKVTEGQQERLERQHWTMTKIQKHQEHILRFASWALESDNNTALLLSKKLIYFQLHRALKMIVDPVEPHGEMKFQWDLNAWTKSAEAFGKIVAERPGTNSTGPGPMAPPRAPGPLSKQGSGSSQPMEVQEGYGFGSDDPYSSAEPHVSGMKRSRSGEGEVSGLLRKVPRVSLERLDLDLTSDSQPPVFKVFPGSTTEDYNLIVIERGAAAAAAGQAGTVPPGAPGAPPLPGMAIVKEEETEAAIGAPPAAPEGPETKPVLMPLTEGPGAEGPRLASPSGSTSSGLEVVAPEVTSAPVSGPGILDDSATICRVCQKPGDLVMCNQCEFCFHLDCHLPALQDVPGEEWSCSLCHVLPDLKEEDGSLSLDGADSTGVVAKLSPANQRKCERVLLALFCHEPCRPLHQLATDSTFSMEQPGGTLDLTLIRARLQEKLSPPYSSPQEFAQDVGRMFKQFNKLTEDKADVQSIIGLQRFFETRMNDAFGDTKFSAVLVEPPPLNLPSAGLSSQELSGPGDGP
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs) (PubMed:20164836, PubMed:22110054, PubMed:25247314, PubMed:27658112). 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 proteasomal 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) (PubMed:20164836). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). 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 (PubMed:22110054, PubMed:27658112). {ECO:0000250|UniProtKB:Q13263, ECO:0000269|PubMed:20164836, ECO:0000269|PubMed:21518874, ECO:0000269|PubMed:22110054, ECO:0000269|PubMed:25247314, ECO:0000269|PubMed:27658112, ECO:0000269|PubMed:9742105}.; FUNCTION: E3 SUMO and ubiquitin ligase that plays a pivotal role in embryonic development, genomic imprinting, and maintenance of genomic stability through repression of repetitive and retroviral elements. Also involved in DNA repair, regulation of innate immunity or cellular energy homeostasis. Acts as a scaffold for assembling transcriptional repression complexes containing methyltransferases, histone deacetylases, and chromatin remodelers. Serves as a nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs), mediating gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1, which methylates histone H3 at 'Lys-9' (H3K9me), leading to heterochromatin formation (PubMed:20164836, PubMed:22110054, PubMed:25247314, PubMed:27658112). In collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Functions as a coactivator for CEBPB and NR3C1 (glucocorticoid receptor) in transcriptional activation of ORM1, and as a corepressor for ERBB4. Inhibits E2F1 activity by promoting E2F1-HDAC1 complex formation and preventing E2F1 acetylation. This contributes to CDKN1A/p21(CIP1) regulation and provides a partial backup to suppress E2F1-mediated apoptosis in the absence of RB1. Mediates the nuclear localization of several KRAB-ZFP transcription factors including KOX1, ZNF268, and ZNF300 among others. 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). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs)(PubMed:20164836). Acts as a corepressor for ZFP568. Beyond its nuclear functions, acts as a positive regulator of type I interferon (IFN-I) signaling by promoting Lys-63-linked ubiquitination of TBK1, facilitating TBK1-IRF3 complex formation. Mediates TRAF6 SUMOylation to regulate its nucleo-cytoplasmic shuttling and modulate activation of the canonical NF-kappa-B signaling pathway. Facilitates SUMOylation of NLRP3, protecting it from 'Lys-48'-linked ubiquitination and proteasomal degradation and thereby enhancing inflammasome activation (By similarity). {ECO:0000250|UniProtKB:Q13263}.
uniprot
proteins
mass_dalton
88847
uniprot
proteins
mutagenesis
MUTAGEN 713..714; /note="CH->WN: In chatwo; hypomorphic mutation with reduced protein stability and impaired transcriptional corepression activity. Embryonic development arrests prior to stage E9, with pronounced convergent extention defects and defective morphogenesis of extra-embryonic tissues. The anterior-posterior axis is shortened and embryos fail to undergo gut closure. No effect on interaction with ZFP568."; /evidence="ECO:0000269|PubMed:22110054
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein sumoylation.
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250|UniProtKB:Q13263}.; 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. {ECO:0000250|UniProtKB:Q13263}.; PTM: Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2. {ECO:0000250|UniProtKB:Q13263}.; PTM: Citrullinated by PADI4. {ECO:0000269|PubMed:24463520}.; PTM: ADP-ribosylated by SIRT6, promoting TRIM28/KAP1 interaction with CBX5, thereby contributing to the packaging of LINE-1 retrotransposon elements into transcriptionally repressive heterochromatin. {ECO:0000269|PubMed:25247314}.
uniprot
proteins
protein_family
TRIM/RBCC family
uniprot
proteins
pubmed
10330177
uniprot
proteins
pubmed
10562550
uniprot
proteins
pubmed
10940561
uniprot
proteins
pubmed
11154279
uniprot
proteins
pubmed
11331580
uniprot
proteins
pubmed
12154074
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16452087
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19321449
uniprot
proteins
pubmed
20164836
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21518874
uniprot
proteins
pubmed
22110054
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
24413057
uniprot
proteins
pubmed
24463520
uniprot
proteins
pubmed
25247314
uniprot
proteins
pubmed
27123980
uniprot
proteins
pubmed
27658112
uniprot
proteins
pubmed
30017584
uniprot
proteins
pubmed
8978696
uniprot
proteins
pubmed
8986806
uniprot
proteins
pubmed
9742105
uniprot
proteins
sequence_length
834
uniprot
proteins
subcellular_location
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}.
uniprot
proteins