PSMD10

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20. [provided by RefSeq]

Full Name

proteasome (prosome, macropain) 26S subunit, non-ATPase, 10

Function

Acts 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 pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.
Acts 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.

Biological Process

Apoptotic processIEA:UniProtKB-KW
Cytoplasmic sequestering of NF-kappaBManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of DNA damage response, signal transduction by p53 class mediatorManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of MAPK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of release of cytochrome c from mitochondriaManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell growthManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cyclin-dependent protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Proteasome regulatory particle assemblyManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cytoplasm
Nucleus