| IED ID | IndEnz0002001776 |
| Enzyme Type ID | protease001776 |
| 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 |
| Gene Name | TRIM28 KAP1 RNF96 TIF1B |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAASAAAASAAAASAASGSPGPGEGSAGGEKRSTAPSAAASASASAAASSPAGGGAEALELLEHCGVCRERLRPEREPRLLPCLHSACSACLGPAAPAAANSSGDGGAAGDGTVVDCPVCKQQCFSKDIVENYFMRDSGSKAATDAQDANQCCTSCEDNAPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRSTGPAKSRDGERTVYCNVHKHEPLVLFCESCDTLTCRDCQLNAHKDHQYQFLEDAVRNQRKLLASLVKRLGDKHATLQKSTKEVRSSIRQVSDVQKRVQVDVKMAILQIMKELNKRGRVLVNDAQKVTEGQQERLERQHWTMTKIQKHQEHILRFASWALESDNNTALLLSKKLIYFQLHRALKMIVDPVEPHGEMKFQWDLNAWTKSAEAFGKIVAERPGTNSTGPAPMAPPRAPGPLSKQGSGSSQPMEVQEGYGFGSGDDPYSSAEPHVSGVKRSRSGEGEVSGLMRKVPRVSLERLDLDLTADSQPPVFKVFPGSTTEDYNLIVIERGAAAAATGQPGTAPAGTPGAPPLAGMAIVKEEETEAAIGAPPTATEGPETKPVLMALAEGPGAEGPRLASPSGSTSSGLEVVAPEGTSAPGGGPGTLDDSATICRVCQKPGDLVMCNQCEFCFHLDCHLPALQDVPGEEWSCSLCHVLPDLKEEDGSLSLDGADSTGVVAKLSPANQRKCERVLLALFCHEPCRPLHQLATDSTFSLDQPGGTLDLTLIRARLQEKLSPPYSSPQEFAQDVGRMFKQFNKLTEDKADVQSIIGLQRFFETRMNEAFGDTKFSAVLVEPPPMSLPGAGLSSQELSGGPGDGP |
| Enzyme Length | 835 |
| Uniprot Accession Number | Q13263 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; |
| DNA Binding | |
| EC Number | 2.3.2.27 |
| Enzyme Function | 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). Acts as a corepressor for ZFP568 (By similarity). {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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein sumoylation. |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (19); Chain (1); Cross-link (29); Domain (1); Helix (13); Initiator methionine (1); Metal binding (8); Modified residue (34); Motif (1); Mutagenesis (23); Natural variant (1); Region (9); Sequence conflict (1); Turn (8); Zinc finger (4) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Chromatin regulator;Citrullination;Coiled coil;Direct protein sequencing;Host-virus interaction;Isopeptide bond;Metal-binding;Nucleus;Phosphoprotein;Reference proteome;Repeat;Repressor;Transcription;Transcription regulation;Transferase;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q13185; P45973; Q12873; P43356; P43357; P43360; Q9UBF1; Q9HCI5; O75376; Q9BQF6; Q8TF47-3; P83917; P23198 |
| Induction | |
| 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:9016654}. Note=Associated with centromeric heterochromatin during cell differentiation through CBX1. {ECO:0000250|UniProtKB:Q62318}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0000269|Ref.5, ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"; MOD_RES 19; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 26; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 50; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 138; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 266; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:Q62318"; MOD_RES 304; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 340; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 377; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 417; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 437; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q62318"; MOD_RES 439; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 453; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 470; /note="Citrulline"; /evidence="ECO:0000250"; MOD_RES 471; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 472; /note="Citrulline"; /evidence="ECO:0000250"; MOD_RES 473; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 479; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 489; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 498; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 501; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 541; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 594; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"; MOD_RES 683; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"; MOD_RES 689; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 697; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 752; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 755; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q62318"; MOD_RES 757; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 770; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 774; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 779; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:Q62318"; MOD_RES 784; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 824; /note="Phosphoserine; by ATM and ATR and dsDNA kinase"; /evidence="ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:20424263" |
| 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}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (3); X-ray crystallography (4) |
| Cross Reference PDB | 1FP0; 2RO1; 2YVR; 6H3A; 6I9H; 6QAJ; 6QU1; |
| Mapped Pubmed ID | 12438698; 14519192; 14743216; 15161933; 15596820; 16169070; 16212417; 16606702; 16954381; 17266347; 17298944; 17314511; 17353931; 17542650; 17620599; 17721511; 18381204; 18590578; 18676401; 19279087; 19321449; 19367725; 19463016; 19498464; 19584288; 19656847; 19682613; 19690564; 19738201; 19805454; 19850934; 19898899; 20032463; 20081839; 20085707; 20221260; 20360068; 20467437; 20515076; 20562859; 20936779; 21170338; 21228624; 21245151; 21252943; 21277283; 21317870; 21343306; 21343339; 21382013; 21652716; 21669397; 21791101; 21851590; 21876767; 21888893; 21911578; 21988832; 22157815; 22205726; 22491012; 22496453; 22513056; 22593156; 22623428; 22715096; 22732494; 22810585; 22863774; 22959342; 22975076; 23034801; 23060449; 23096706; 23416715; 23548070; 23606334; 23645532; 23645696; 23678292; 23740979; 23902751; 23935532; 23991171; 24018422; 24189400; 24434549; 24635384; 24696491; 24780295; 24861921; 24907272; 24983967; 25092915; 25107531; 25160591; 25173174; 25419715; 25421577; 25548895; 25609649; 25818296; 25846574; 25852190; 25905708; 25948750; 25960296; 25995248; 26055329; 26081272; 26158765; 26293668; 26476730; 26496610; 26537675; 26572645; 26725010; 26766492; 26824653; 27095111; 27364555; 27412325; 27432546; 27501258; 27588518; 27601472; 27779468; 27780869; 27845900; 27922110; 27976729; 28052240; 28068325; 28159803; 28249048; 28381187; 28498400; 28763864; 28864417; 28869544; 28895414; 29146583; 29198826; 29284678; 29290627; 29393469; 29569972; 29581310; 29610526; 29631612; 29728366; 29912901; 29917268; 29955894; 30061100; 30206173; 30309319; 30323812; 30360396; 30479348; 30543698; 30652970; 30694527; 31000713; 31028095; 31204252; 31289231; 31427381; 32061892; 32068487; 32133046; 32156811; 32402252; 32673994; 32796077; 32900933; 33091876; 33326746; 33398366; 33514850; 33565090; 33657380; 34100380; 34373456; 34440702; 34500575; 34518220; 34903241; 8183939; |
| Motif | MOTIF 481..494; /note=PxVxL motif |
| Gene Encoded By | |
| Mass | 88,550 |
| Kinetics | |
| Metal Binding | METAL 153; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 156; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 177; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 181; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 209; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 212; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 232; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024; METAL 237; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00024 |
| Rhea ID | |
| Cross Reference Brenda |