TRIM28
entrez
10155
canonical
uniprot
Q13263
canonical
ensembl
ENSG00000130726
resolver
ensp
ENSP00000253024
resolver
genesymbol
TRIM28
resolver
genesymbol_syn
KAP1
resolver
genesymbol_syn
RNF96
resolver
genesymbol_syn
TIF1B
resolver
hgnc
HGNC:16384
resolver
uniprot
O00677
resolver
uniprot
Q7Z632
resolver
uniprot
Q93040
resolver
uniprot
Q96IM1
resolver
uniprot_entry
TIF1B_HUMAN
resolver
uniprot_sec
O00677
resolver
uniprot_sec
Q7Z632
resolver
uniprot_sec
Q93040
resolver
uniprot_sec
Q96IM1
resolver
amino_acid_sequence
MAASAAAASAAAASAASGSPGPGEGSAGGEKRSTAPSAAASASASAAASSPAGGGAEALELLEHCGVCRERLRPEREPRLLPCLHSACSACLGPAAPAAANSSGDGGAAGDGTVVDCPVCKQQCFSKDIVENYFMRDSGSKAATDAQDANQCCTSCEDNAPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRSTGPAKSRDGERTVYCNVHKHEPLVLFCESCDTLTCRDCQLNAHKDHQYQFLEDAVRNQRKLLASLVKRLGDKHATLQKSTKEVRSSIRQVSDVQKRVQVDVKMAILQIMKELNKRGRVLVNDAQKVTEGQQERLERQHWTMTKIQKHQEHILRFASWALESDNNTALLLSKKLIYFQLHRALKMIVDPVEPHGEMKFQWDLNAWTKSAEAFGKIVAERPGTNSTGPAPMAPPRAPGPLSKQGSGSSQPMEVQEGYGFGSGDDPYSSAEPHVSGVKRSRSGEGEVSGLMRKVPRVSLERLDLDLTADSQPPVFKVFPGSTTEDYNLIVIERGAAAAATGQPGTAPAGTPGAPPLAGMAIVKEEETEAAIGAPPTATEGPETKPVLMALAEGPGAEGPRLASPSGSTSSGLEVVAPEGTSAPGGGPGTLDDSATICRVCQKPGDLVMCNQCEFCFHLDCHLPALQDVPGEEWSCSLCHVLPDLKEEDGSLSLDGADSTGVVAKLSPANQRKCERVLLALFCHEPCRPLHQLATDSTFSLDQPGGTLDLTLIRARLQEKLSPPYSSPQEFAQDVGRMFKQFNKLTEDKADVQSIIGLQRFFETRMNEAFGDTKFSAVLVEPPPMSLPGAGLSSQELSGGPGDGP
uniprot
proteins
disease_involvement
DISEASE: Wilms tumor 7 (WT7) [MIM:621332]: A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells. {ECO:0000269|PubMed:29912901, ECO:0000269|PubMed:30694527, ECO:0000269|PubMed:30885698}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
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. In collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). 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) (PubMed:23543754). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). 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 (PubMed:38495890). Mediates TRAF6 SUMOylation to regulate its nucleo-cytoplasmic shuttling and modulate activation of the canonical NF-kappa-B signaling pathway (PubMed:39920527). Facilitates SUMOylation of NLRP3, protecting it from 'Lys-48'-linked ubiquitination and proteasomal degradation and thereby enhancing inflammasome activation (PubMed:34373456). {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:38495890, ECO:0000269|PubMed:39920527, ECO:0000269|PubMed:41109928, 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}.; FUNCTION: (Microbial infection) Plays a positive role in SARS-CoV-2 virulence by mediating SUMOylation of nucleoprotein that promotes its RNA association leading to viral replication and innate antiviral immunity inhibition. {ECO:0000269|PubMed:38172120}.
uniprot
proteins
mass_dalton
88550
uniprot
proteins
mutagenesis
MUTAGEN 65; /note="C->A: Reduces nuclear localization activity of ZNF268 and loss of E3 ligase activity; when associated with A-68."; /evidence="ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:38495890"; MUTAGEN 68; /note="C->A: Reduces nuclear localization activity of ZNF268 and loss of E3 ligase activity; when associated with A-65. Loss of E3 ligase activity."; /evidence="ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:38495890"; MUTAGEN 232; /note="C->S: Strongly reduced palmitoylation."; /evidence="ECO:0000269|PubMed:41109928"; MUTAGEN 306; /note="L->P: Disrupts the interaction with ZNF350 and amost completely relieves the transcription repressive effect of sumoylated TRIM28."; /evidence="ECO:0000269|PubMed:17942393"; MUTAGEN 366; /note="K->G: Greatly reduced interaction with PPP1CA."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 368; /note="I->G: Increased interaction with PPP1CA. Greatly decreased phosphorylation on S-824."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 370; /note="F->A: Some reduction in interaction with PPP1CA."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 370; /note="F->G: Some reduction in interaction with PPP1CA."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 440; /note="S->A: No effect on interaction with PPP1CA nor on sumoylation levels. Decreased sumoylation levels; when associated with D-501 and D-824."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 488; /note="V->E: Abolishes interaction with CBX5; when associated with E-490."; /evidence="ECO:0000269|PubMed:20562864"; MUTAGEN 490; /note="L->E: Abolishes interaction with CBX5; when associated with E-488."; /evidence="ECO:0000269|PubMed:20562864"; MUTAGEN 501; /note="S->A: No effect on interaction with PPP1CA nor on sumoylation levels. Decreased sumoylation levels; when associated with D-440 and D-824."; /evidence="ECO:0000269|PubMed:20424263"; MUTAGEN 554; /note="K->R: Moderately reduces sumoylation and repression. Abolishes both sumoylation and repression; when associated with R-575. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-779 and R-804."; /evidence="ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18082607"; MUTAGEN 575; /note="K->R: Modestly reduced sumoylation and repression. Abolishes both sumoylation and repression; when associated with R-554."; /evidence="ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:18082607"; MUTAGEN 651; /note="C->A: Complete loss of the PHD finger-mediated stimulatory effect on sumoylation. Loss of binding UBE2I. Loss of catalytic activity."; /evidence="ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:18488044, ECO:0000269|PubMed:38172120"; MUTAGEN 653; /note="L->A: Greatly reduced sumoylation. Little further effect on sumoylation; when associated with A-668 and/or A-709."; /evidence="ECO:0000269|PubMed:18488044"; MUTAGEN 668; /note="L->A: Little effect on sumoylation. Little further effect on sumoylation; when associated with A-653 and/or A-709."; /evidence="ECO:0000269|PubMed:18488044"; MUTAGEN 676; /note="K->R: Modestly reduces sumoylation and repression."; /evidence="ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:18082607"; MUTAGEN 709; /note="L->A: Greatly reduced sumoylation. Little further effect on sumoylation; when associated with A-653 and/or A-668."; /evidence="ECO:0000269|PubMed:18488044"; MUTAGEN 750; /note="K->R: Some reduced sumoylation and repression."; /evidence="ECO:0000269|PubMed:18082607"; MUTAGEN 779; /note="K->R: Abolishes both sumoylation and repression; when associated with R-804. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-554 and R-804."; /evidence="ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18082607"; MUTAGEN 804; /note="K->R: Abolishes both sumoylation and repression; when associated with R-779. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-554 and R-779."; /evidence="ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18082607"; MUTAGEN 824; /note="S->A: Suppresses Dox-induced CDKN1A/p21 promoter activation. No effect on sumoylation levels. Decreased sumoylation levels; when associated with D-440 and D-501."; /evidence="ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:20424263"; MUTAGEN 824; /note="S->D: Enhances Dox-induced CDKN1A/p21 promoter activation. Decreased sumoylation with or without Dox-treatment."; /evidence="ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:20424263
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein sumoylation.; PATHWAY: Protein modification; protein ubiquitination.
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:0000269|PubMed:16862143, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:20424263}.; 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:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18488044, ECO:0000269|PubMed:20388717, ECO:0000269|PubMed:20424263}.; PTM: Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2. {ECO:0000269|PubMed:20864041}.; PTM: Citrullinated by PADI4. {ECO:0000250|UniProtKB:Q62318}.; 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:0000250|UniProtKB:Q62318}.; PTM: SUMOylated, SUMOylation is enhanced by the transcriptional regulator KAISO. {ECO:0000269|PubMed:39847191}.; PTM: Palmitoylated at Cys-232 by ZDHHC20. This modification is required for DNA damage repair. {ECO:0000269|PubMed:41109928}.
uniprot
proteins
protein_family
TRIM/RBCC family
uniprot
proteins
pubmed
10330177
uniprot
proteins
pubmed
10347202
uniprot
proteins
pubmed
11013263
uniprot
proteins
pubmed
11226167
uniprot
proteins
pubmed
11230151
uniprot
proteins
pubmed
11959841
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15882967
uniprot
proteins
pubmed
16107876
uniprot
proteins
pubmed
16792528
uniprot
proteins
pubmed
16862143
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17056014
uniprot
proteins
pubmed
17079232
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17178852
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17512541
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17704056
uniprot
proteins
pubmed
17924679
uniprot
proteins
pubmed
17942393
uniprot
proteins
pubmed
17942928
uniprot
proteins
pubmed
18060868
uniprot
proteins
pubmed
18082607
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18488044
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18675275
uniprot
proteins
pubmed
19367720
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19710015
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20388717
uniprot
proteins
pubmed
20424263
uniprot
proteins
pubmed
20562864
uniprot
proteins
pubmed
20858735
uniprot
proteins
pubmed
20864041
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21549307
uniprot
proteins
pubmed
21940674
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23034801
uniprot
proteins
pubmed
23149945
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23543754
uniprot
proteins
pubmed
23665872
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24623306
uniprot
proteins
pubmed
24657165
uniprot
proteins
pubmed
24741090
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25593309
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
27029610
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29912901
uniprot
proteins
pubmed
30042493
uniprot
proteins
pubmed
30694527
uniprot
proteins
pubmed
30885698
uniprot
proteins
pubmed
31856708
uniprot
proteins
pubmed
32051553
uniprot
proteins
pubmed
32890405
uniprot
proteins
pubmed
33154469
uniprot
proteins
pubmed
34373456
uniprot
proteins
pubmed
37823600
uniprot
proteins
pubmed
38172120
uniprot
proteins
pubmed
38495890
uniprot
proteins
pubmed
39847191
uniprot
proteins
pubmed
39920527
uniprot
proteins
pubmed
41109928
uniprot
proteins
pubmed
8769649
uniprot
proteins
pubmed
9016654
uniprot
proteins
sequence_length
835
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10330177, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24741090, ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:41109928, ECO:0000269|PubMed:9016654}. Note=Associated with centromeric heterochromatin during cell differentiation through CBX1 (By similarity). Localizes to sites of DNA damage (PubMed:25593309). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:25593309}.
uniprot
proteins