| IED ID | IndEnz0002007473 |
| Enzyme Type ID | protease007473 |
| Protein Name |
Proteasome subunit beta type-8 EC 3.4.25.1 Low molecular mass protein 7 Macropain subunit C13 Multicatalytic endopeptidase complex subunit C13 Proteasome component C13 Proteasome subunit beta-5i Really interesting new gene 10 protein |
| Gene Name | PSMB8 LMP7 PSMB5i RING10 Y2 |
| 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 | MALLDVCGAPRGQRPESALPVAGSGRRSDPGHYSFSMRSPELALPRGMQPTEFFQSLGGDGERNVQIEMAHGTTTLAFKFQHGVIAAVDSRASAGSYISALRVNKVIEINPYLLGTMSGCAADCQYWERLLAKECRLYYLRNGERISVSAASKLLSNMMCQYRGMGLSMGSMICGWDKKGPGLYYVDEHGTRLSGNMFSTGSGNTYAYGVMDSGYRPNLSPEEAYDLGRRAIAYATHRDSYSGGVVNMYHMKEDGWVKVESTDVSDLLHQYREANQ |
| Enzyme Length | 276 |
| Uniprot Accession Number | P28062 |
| Absorption | |
| Active Site | ACT_SITE 73; /note=Nucleophile; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleavage of peptide bonds with very broad specificity.; EC=3.4.25.1; |
| DNA Binding | |
| EC Number | 3.4.25.1 |
| Enzyme Function | FUNCTION: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes. {ECO:0000269|PubMed:16423992, ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:21881205, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:8163024}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (1); Beta strand (12); Chain (1); Helix (6); Modified residue (1); Natural variant (8); Propeptide (1); Region (1); Site (1); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Cytoplasm;Differentiation;Disease variant;Host-virus interaction;Hydrolase;Immunity;Nucleus;Phosphoprotein;Protease;Proteasome;Reference proteome;Threonine protease;Zymogen |
| Interact With | P27958; P05067; P54253; Q9BVJ7; Q96EK6; P28799; P04792; P42858; Q0VD86; O60333-2; O15116; Q6FHY5; Q8NI38; Q99471; P62487; Q04864-2; Q9Y3C5; Q9Y5X3-2; P00441; Q13148; Q96A09; Q13114; Q15645; Q5T6F2; O76024; Q9NZC7-5; A6XGL0; Q9H0C1 |
| Induction | INDUCTION: Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up-regulated by heat shock treatment. {ECO:0000269|PubMed:11493458, ECO:0000269|PubMed:15501285, ECO:0000269|PubMed:15907481, ECO:0000269|PubMed:17142736, ECO:0000269|PubMed:17262812, ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:19525961, ECO:0000269|PubMed:19619915, ECO:0000269|PubMed:8663318}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00809}. Nucleus {ECO:0000250}. |
| Modified Residue | MOD_RES P28062-2:5; /note=Phosphothreonine; /evidence=ECO:0000305 |
| Post Translational Modification | PTM: Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity. {ECO:0000250|UniProtKB:O35955}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (20) |
| Cross Reference PDB | 5L5A; 5L5B; 5L5D; 5L5E; 5L5F; 5L5H; 5L5I; 5L5J; 5L5O; 5L5P; 5L5Q; 5L5R; 5L5S; 5L5T; 5L5U; 5L5V; 5LTT; 5M2B; 6AVO; 6E5B; 7AWE; |
| Mapped Pubmed ID | 10075690; 10205060; 10375532; 10514433; 10559916; 10693759; 10797013; 10828887; 10918611; 11046155; 11051286; 11092454; 11259415; 11285280; 11292861; 11292862; 11337497; 11350924; 11404376; 11454738; 11494532; 11566882; 11585840; 11585921; 11669176; 11737038; 11739726; 11772516; 11793848; 11842200; 11931757; 12029096; 12070128; 12101228; 12136087; 12209365; 12225333; 12519221; 12600938; 12648225; 12660156; 12682069; 12738770; 12750368; 12808096; 12816948; 12853446; 14508489; 14508490; 14528300; 14551602; 14561893; 14564014; 14676825; 14684739; 14707141; 14734113; 14757770; 14769151; 15014503; 15029244; 15047845; 15084608; 15224091; 15224092; 15226418; 15231747; 15257295; 15282312; 15303969; 15469984; 15571818; 15603870; 15678106; 15678131; 15735756; 15781449; 16009940; 16171779; 16224524; 16338279; 16371461; 16396320; 16413484; 16421275; 16547521; 16611981; 16705181; 16707496; 16728642; 16818754; 16931761; 17115028; 17139257; 17183061; 17187060; 17218260; 17234884; 17283082; 1730654; 17491658; 17525827; 17581627; 17703412; 18248301; 18497827; 18541707; 18997794; 19037255; 19065646; 19148137; 19202550; 19258923; 19379695; 19404951; 19473982; 19526842; 19573811; 19684112; 19759537; 19808967; 19851445; 19913121; 19955409; 20028659; 20153157; 20154143; 20331378; 20360384; 20470844; 20503287; 20525414; 20628086; 20711500; 20723761; 20818436; 20858899; 20956384; 21303409; 21357747; 21362330; 21478859; 21529441; 21532586; 21799911; 21804012; 21921029; 22037870; 2211721; 22306028; 22306998; 22427670; 22925930; 23018640; 23121362; 23283737; 23333871; 23661552; 23867461; 24012004; 24019521; 25098831; 25260729; 25547115; 25654763; 26091038; 26183061; 26542806; 26778333; 26894977; 26944796; 27098790; 27100179; 27132469; 27156327; 27213585; 27789522; 28098422; 28207947; 28700671; 28721901; 29039469; 29073155; 29167449; 29428669; 29451304; 29510614; 29775672; 30279279; 30485383; 31283222; 31503210; 31559672; 31836918; 32128987; 32221071; 32255680; 32680979; 32782149; 32943490; 33109760; 33610037; 33798908; 34045234; 6162102; 6548414; 7479848; 7479976; 7575604; 7628694; 7809113; 7831327; 7862124; 7957109; 9096384; 9362451; 9380723; 9635433; 9660940; 9859996; 9861020; 9990853; |
| Motif | |
| Gene Encoded By | |
| Mass | 30,354 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |