| IED ID | IndEnz0002009881 |
| Enzyme Type ID | protease009881 |
| Protein Name |
Proteasome activator complex subunit 3 11S regulator complex subunit gamma REG-gamma Activator of multicatalytic protease subunit 3 Ki nuclear autoantigen Proteasome activator 28 subunit gamma PA28g PA28gamma |
| Gene Name | PSME3 |
| 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 | MASLLKVDQEVKLKVDSFRERITSEAEDLVANFFPKKLLELDSFLKEPILNIHDLTQIHSDMNLPVPDPILLTNSHDGLDGPTYKKRRLDECEEAFQGTKVFVMPNGMLKSNQQLVDIIEKVKPEIRLLIEKCNTVKMWVQLLIPRIEDGNNFGVSIQEETVAELRTVESEAASYLDQISRYYITRAKLVSKIAKYPHVEDYRRTVTEIDEKEYISLRLIISELRNQYVTLHDMILKNIEKIKRPRSSNAETLY |
| Enzyme Length | 254 |
| Uniprot Accession Number | P61289 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978). {ECO:0000269|PubMed:10835274, ECO:0000269|PubMed:11185562, ECO:0000269|PubMed:11432824, ECO:0000269|PubMed:15111123, ECO:0000269|PubMed:18309296, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:9325261}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Chain (1); Initiator methionine (1); Modified residue (5); Mutagenesis (1); Sequence conflict (2) |
| Keywords | Acetylation;Alternative splicing;Apoptosis;Cell cycle;Cytoplasm;Direct protein sequencing;Host-virus interaction;Nucleus;Phosphoprotein;Proteasome;Reference proteome |
| Interact With | A0A0S2Z645; P54259; Q86V38; Q9BXC9; P30305; Q86X02; P38432; A0A140G945; Q14689-6; Q9NQL9; Q92997; Q96JC9; Q96CJ1; Q6PCT2-2; Q9Y3I1; Q9NU39; Q9NWQ4-1; P31942-2; Q15735; Q8WVZ9; Q92876; Q8TBB1; Q00987; Q6FHY5; Q9Y6Q9; Q96HA8; Q99471; Q9NRD5; O43741; Q9NZ81; Itself; Q9UNE2; P42677; Q9HCE7; Q9UQ90; Q32MN6; Q9P2Z0; Q8WVP5; P04637; Q99757; Q64LD2-2; Q8TBK6; P0DTC9; P12504; O93077 |
| Induction | INDUCTION: Up-regulated in thyroid carcinoma cells. {ECO:0000269|PubMed:12629132}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10657252, ECO:0000269|PubMed:12629132}. Cytoplasm {ECO:0000250}. Note=Localizes to the cytoplasm during mitosis following nuclear envelope breakdown at this distinct stage of the cell cycle which allows its interaction with MAP3K3 kinase. {ECO:0000250}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22814378"; MOD_RES 17; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 24; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 195; /note="N6-acetyllysine; by P300/CBP"; /evidence="ECO:0000269|PubMed:23612972"; MOD_RES 247; /note="Phosphoserine; by CHEK2"; /evidence="ECO:0000269|PubMed:25361978" |
| Post Translational Modification | PTM: Phosphorylated by MAP3K3 (By similarity). Phosphorylation at Ser-247 promotes its association with CCAR2. {ECO:0000250|UniProtKB:P61290, ECO:0000269|PubMed:25361978}.; PTM: Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1. {ECO:0000269|PubMed:23612972, ECO:0000269|Ref.9}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10075690; 10205060; 10375532; 10514433; 10559916; 10693759; 10797013; 10828887; 10918611; 11046155; 11259415; 11285280; 11292861; 11292862; 11350924; 11454738; 11566882; 11585840; 11585921; 11739726; 11842200; 11859414; 11931757; 12070128; 12101228; 12136087; 12600938; 12660156; 12682069; 12738770; 12750368; 12784391; 12808096; 12816948; 12853446; 12970408; 14508489; 14508490; 14528300; 14561893; 14564014; 14676825; 14684739; 14707141; 14734113; 14743216; 14757770; 15014503; 15029244; 15084608; 15224091; 15224092; 15226418; 15257295; 15282312; 15469984; 15571818; 15678106; 15678131; 15735756; 15781449; 16169070; 16171779; 16189514; 16371461; 16413484; 16421275; 16439211; 16547521; 16611981; 16705181; 16707496; 16713569; 16728642; 16818754; 16931761; 17043677; 17088425; 17115028; 17139257; 17183061; 17187060; 17218260; 17234884; 17283082; 17327906; 17353931; 17446270; 18235248; 18321762; 18343811; 18497827; 18541707; 18985028; 18997794; 19091860; 19379695; 19473982; 19549727; 19556897; 19573811; 19596235; 19615732; 19656465; 19684112; 19738201; 19759537; 19808967; 19955409; 20028659; 20154143; 20360384; 20467919; 20494959; 20562859; 20580715; 20683941; 20719955; 20818436; 20858899; 20956384; 21084564; 21216954; 21282530; 21357747; 21445096; 21478859; 21516116; 21532586; 21799911; 21921029; 22042974; 22134242; 22190034; 22306028; 22306998; 22427670; 22623428; 22938444; 23104922; 23333871; 23414517; 23602568; 23661552; 23867461; 24012004; 24019521; 24113729; 24157709; 24531141; 24811749; 24901344; 25260729; 25416956; 25482151; 25490392; 25511742; 25547115; 25550823; 25654763; 25697482; 25908095; 25936920; 26091038; 26183061; 26201457; 26425675; 26425691; 26496610; 26542806; 26638075; 26752685; 26778333; 26944602; 27511885; 27756569; 28529105; 28605165; 29020881; 29437787; 29509725; 29611800; 29702196; 29795381; 30602418; 31243343; 31282281; 31491459; 31596196; 31605415; 31630568; 32424140; 32568029; 33230243; 33262340; 33562807; 33933312; 34913092; 7479848; 7479976; 7575604; 7628694; 7809113; 7831327; 7862124; 7957109; 9362451; 9380723; 9635433; 9660940; 9859996; 9990853; |
| Motif | |
| Gene Encoded By | |
| Mass | 29,506 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |