InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PSMD10

Summary

InnateDB Protein

IDBP-81757.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PSMD10

Protein Name

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

Synonyms

dJ889N15.2; p28; p28(GANK);

Species

Homo sapiens

Ensembl Protein

ENSP00000217958

InnateDB Gene

IDBG-81755 (PSMD10)

Protein Structure

UniProt Annotation

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 pahway, 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.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:18040287}. Nucleus {ECO:0000269PubMed:18040287}.

Disease Associations

Tissue Specificity

Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level). {ECO:0000269PubMed:10613832, ECO:0000269PubMed:20628200}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 89 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	89 [view]
Protein-Protein	84 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008134	transcription factor binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000209	protein polyubiquitination
GO:0000278	mitotic cell cycle
GO:0002474	antigen processing and presentation of peptide antigen via MHC class I
GO:0002479	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
GO:0006521	regulation of cellular amino acid metabolic process
GO:0006915	apoptotic process
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007253	cytoplasmic sequestering of NF-kappaB
GO:0010467	gene expression
GO:0016032	viral process
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0030307	positive regulation of cell growth
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031398	positive regulation of protein ubiquitination
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034641	cellular nitrogen compound metabolic process
GO:0042590	antigen processing and presentation of exogenous peptide antigen via MHC class I
GO:0042981	regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043409	negative regulation of MAPK cascade
GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0044281	small molecule metabolic process
GO:0045737	positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0051436	negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051437	positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0070682	proteasome regulatory particle assembly
GO:0090201	negative regulation of release of cytochrome c from mitochondria

Cellular Component

GO:0000502	proteasome complex
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005838	proteasome regulatory particle
GO:0008540	proteasome regulatory particle, base subcomplex
GO:0045111	intermediate filament cytoskeleton