| IED ID | IndEnz0002008719 |
| Enzyme Type ID | protease008719 |
| Protein Name |
Protein SET HLA-DR-associated protein II Inhibitor of granzyme A-activated DNase IGAAD PHAPII Phosphatase 2A inhibitor I2PP2A I-2PP2A Template-activating factor I TAF-I |
| Gene Name | SET |
| 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 | MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKGEKEQQEAIEHIDEVQNEIDRLNEQASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYLTRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLTKRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDDEEGEGEEDDDDDEEEEGLEDIDEEGDEDEGEEDEDDDEGEEGEEDEGEDD |
| Enzyme Length | 290 |
| Uniprot Accession Number | Q01105 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (5); Chain (1); Compositional bias (2); Cross-link (1); Helix (8); Initiator methionine (1); Modified residue (11); Natural variant (4); Region (5); Site (1); Turn (1) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Chaperone;Chromosomal rearrangement;Cytoplasm;DNA-binding;Direct protein sequencing;Disease variant;Endoplasmic reticulum;Host-virus interaction;Isopeptide bond;Mental retardation;Methylation;Nucleus;Phosphoprotein;Proto-oncogene;Reference proteome;Ubl conjugation |
| Interact With | Q6SJ93; Q12778; Q00987; P50222; P10644; P63000; O00560; Q15573; Q53T94; Q15572; P20226; Q9BT49; P17480; Q53HL2; Q6SJ93; Q92993; Q8TAP4-4; P26367; P17252; Q9BWE0-4; O00560; Q15047-2; Q562F6-3; Q7Z699; Q5T0J7-2; Q9BT49; Q08117-2; P61981; P17021; Q7Z4V0; Q49A12 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. The SET complex is associated with the endoplasmic reticulum. Following CTL attack and cleavage by GZMA, moves rapidly to the nucleus, where it is found in the nucleoplasm, avoiding the nucleolus. Similar translocation to the nucleus is also observed for lymphocyte-activated killer cells after the addition of calcium. |
| Modified Residue | MOD_RES 2; /note="N,N,N-trimethylalanine"; /evidence="ECO:0000250|UniProtKB:Q9EQU5"; MOD_RES 7; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"; MOD_RES 28; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 63; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 68; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:Q9EQU5"; MOD_RES 146; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q9EQU5"; MOD_RES 150; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 172; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES Q01105-2:11; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES Q01105-2:15; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"; MOD_RES Q01105-2:24; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" |
| Post Translational Modification | PTM: Isoform 2 is phosphorylated on Ser-15 and Ser-24.; PTM: Isoform 2 is acetylated on Lys-11.; PTM: Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group (By similarity). {ECO:0000250}.; PTM: N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity). {ECO:0000250}.; PTM: [Isoform 2]: Cleaved after Lys-176 by GZMA. The cleavage inhibits its nucleosome assembly activity and disrupts the inhibition on NME1. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 2E50; 7MTO; |
| Mapped Pubmed ID | 11018049; 11741927; 11978794; 12407107; 12444089; 14671643; 14743216; 15039562; 15136563; 15161933; 15173575; 15257295; 15556635; 15930275; 15931263; 16061203; 16189514; 16212417; 16286244; 16823850; 16861234; 17008916; 17034827; 17178712; 17245428; 17296573; 17309103; 17318177; 17353931; 17529993; 17608644; 17620317; 17868381; 17875674; 18096310; 18374643; 18457437; 18591933; 18649364; 18718915; 18809386; 18931446; 19028839; 19130553; 19166587; 19234487; 19367725; 19615732; 19738201; 19900756; 20195357; 20360068; 20562859; 20634891; 20693670; 20800572; 21044950; 21156847; 21289314; 21515671; 21720744; 21725597; 21806989; 21844565; 21911480; 21940793; 21988832; 22133779; 22143534; 22466417; 22496234; 22677993; 22739068; 22796192; 23106910; 23195690; 23251465; 23374587; 23414517; 23691099; 23902751; 24025258; 24305947; 24436473; 24449214; 24508256; 24555657; 24621013; 24849368; 24927563; 24935721; 24983498; 25128526; 25152373; 25234598; 25388166; 25416956; 25609649; 25656576; 25760096; 25818296; 25945834; 26115722; 26216969; 26496610; 26563471; 26575017; 26752685; 26876205; 27035430; 27351675; 27383536; 27517624; 27613868; 27626385; 27796741; 27836688; 28356029; 28402964; 28460463; 28636114; 28677734; 28781233; 28977641; 29106904; 29852409; 29907757; 30224541; 30443898; 30658075; 31176779; 31227592; 31495599; 31527146; 31913266; 32071079; 32267167; 32973131; 33909454; 34021475; |
| Motif | |
| Gene Encoded By | |
| Mass | 33,489 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |