26S proteasome non-ATPase regulatory subunit 10 (PSMD10)
The protein contains 226 amino acids for an estimated molecular weight of 24428 Da.
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. (updated: Nov. 22, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Anaphase-promoting complex-dependent catabolic process
Antigen processing and presentation of exogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Antigen processing and presentation of peptide antigen via MHC class I
Apoptotic process
Cellular nitrogen compound metabolic process
Cytoplasmic sequestering of NF-kappaB
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Fc-epsilon receptor signaling pathway
G1/S transition of mitotic cell cycle
Gene expression
Interleukin-1-mediated signaling pathway
MAPK cascade
Mitotic cell cycle
Negative regulation of apoptotic process
Negative regulation of canonical Wnt signaling pathway
Negative regulation of DNA damage response, signal transduction by p53 class mediator
Negative regulation of G2/M transition of mitotic cell cycle
Negative regulation of MAPK cascade
Negative regulation of NF-kappaB transcription factor activity
Negative regulation of release of cytochrome c from mitochondria
Negative regulation of transcription by RNA polymerase II
NIK/NF-kappaB signaling
Obsolete negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Positive regulation of canonical Wnt signaling pathway
Positive regulation of cell growth
Positive regulation of cyclin-dependent protein serine/threonine kinase activity
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of protein ubiquitination
Post-translational protein modification
Pre-replicative complex assembly
Proteasome regulatory particle assembly
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein polyubiquitination
Regulation of apoptotic process
Regulation of cellular amino acid metabolic process
Regulation of hematopoietic stem cell differentiation
Regulation of mitotic cell cycle phase transition
Regulation of mRNA stability
Regulation of transcription by RNA polymerase II
Regulation of transcription from RNA polymerase II promoter in response to hypoxia
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Small molecule metabolic process
Stimulatory C-type lectin receptor signaling pathway
T cell receptor signaling pathway
Transmembrane transport
Tumor necrosis factor-mediated signaling pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
The reference OMIM entry for this protein is 300880
Proteasome 26s subunit, non-atpase, 10; psmd10
P28
Gankyrin
P28(gank)
DESCRIPTION
Ubiquitinated proteins are degraded by a 26S ATP-dependent protease. The protease is composed of a 20S catalytic proteasome and PA700, a 700-kD regulatory complex (see PSMC1, 602706) that includes PSMD10 (Hori et al., 1998).CLONING
Hori et al. (1998) determined the partial protein sequences of bovine p28 and p40.5 (PSMD13; 603481), 2 components of PA700. By searching a sequence database, they identified cDNAs encoding the human p28 and p40.5 homologs, and they cloned the cDNAs from a U937 monocyte cDNA library. The predicted 226-amino acid human p28 protein contains 5 ankyrin repeats, which are thought to function in protein-protein interactions. Using computerized homology searches, Hori et al. (1998) identified Nas6, an S. cerevisiae gene encoding a protein with 38% identity to p28. Northern blot analysis revealed that p28 was expressed as a 1.3-kb mRNA in all human tissues tested.GENE FUNCTION
Hori et al. (1998) found that disruption of yeast Nas6 had no effect on cell viability. Man et al. (2010) found that expression of constitutively active mutant RAS (HRAS; 190020) increased gankyrin mRNA and protein expression and induced a tumorigenic phenotype in transfected NIH3T3 mouse fibroblasts. Knockdown of gankyrin reversed RAS-induced transformation and tumorigenesis. Gankyrin was highly expressed in human lung cancers expressing RAS with oncogenic mutations, and gankyrin expression was higher in adenocarcinomas than in squamous carcinomas. Knockdown and molecular studies performed predominantly with mouse cells revealed that gankyrin increased interaction between Rhoa (165390) and its inhibitor Rhogdi (ARHGDIA; 601925), resulting in elevated Akt (see 164730) activation via the Rhoa-Rock (see 601702)-Pten (601728) pathway. Knockdown of Rock or deletion of Pten reversed gankyrin-mediated Akt activation. Dong et al. (2011) stated that p28(GANK) is highly expressed in human hepatocellular carcinoma (HCC) cells. Using a reporter gene assay with HepG2 and HEK293 cells, they found that the growth factors EGF (131530) and HGF (142409), in addition to RAS, elevated p28(GANK) mRNA and protein expression in a dose-dependent manner. Molecular and inhibitor studies revealed that this activation of p28(GANK) occurred through the PI3 kinase (see 601232)-AKT signaling pathway. In 40 primary HCC samples, p28(GANK) protein levels correlated with AKT activation. Beta-catenin (see 116806) and MYC (190080) also activated p28(GANK) expression, and p28(GANK) increased beta-catenin signaling in a positive-feedback loop. p28(GNAK) appeared to increase beta-catenin signaling by releasing it from cytoskeletal sequestration in complex with E-cadherin (CDH1; 192090). Zhen et al. (2013) found that gankyrin was highly overexpressed in human breast cancers and that gankyrin expression correlated strongly with lymph node metastasis. In cultured human breast cancer cells, knockdown of gankyrin reduced cell migration and increased cell adhesion, with formation of large focal adhesions. Expression of constitutively active RAC1 (602048) reversed the effects of gankyrin knockdown. Overexpression of gankyrin accelerated focal adhesion turnover and increased cell migration.MAPPING
Hartz (2012) mapped the PSMD10 gene to chromosome Xq22.32 based on an alignment of the PSMD10 sequence (GenBank GENBANK AB009619) with the genomic sequence (GRCh37). ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 300880 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed