MGP Database

MGP002501

UniProt Annotations

Entry Information
Gene Nameproteasome (prosome, macropain) 26S subunit, non-ATPase, 10
Protein EntryPSD10_HUMAN
UniProt IDO75832
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O75832-1; Sequence=Displayed; Name=2; IsoId=O75832-2; Sequence=VSP_043043;
CautionWas initially identified as a genuine component of the 26S proteasome. {ECO:0000305}.
FunctionActs as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.
FunctionActs as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.
InteractionP43358:MAGEA4; NbExp=5; IntAct=EBI-752185, EBI-743122; P43686:PSMC4; NbExp=8; IntAct=EBI-752185, EBI-743997;
SimilarityContains 7 ANK repeats. {ECO:0000255|PROSITE- ProRule:PRU00023}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:18040287}. Nucleus {ECO:0000269|PubMed:18040287}.
SubunitPart of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK. {ECO:0000269|PubMed:10613832, ECO:0000269|PubMed:11779854, ECO:0000269|PubMed:11900540, ECO:0000269|PubMed:16023600, ECO:0000269|PubMed:18040287, ECO:0000269|PubMed:19490896, ECO:0000269|PubMed:20628200}.
Tissue SpecificityTends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level). {ECO:0000269|PubMed:10613832, ECO:0000269|PubMed:20628200}.
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