26S proteasome non-ATPase regulatory subunit 4 (PSMD4)
The protein contains 377 amino acids for an estimated molecular weight of 40737 Da.
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
(right-click above to access to more options from the contextual menu)
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
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 G2/M transition of mitotic cell cycle
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
Post-translational protein modification
Pre-replicative complex assembly
Proteasome 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 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 601648
Proteasome 26s subunit, non-atpase, 4; psmd4
Protease 26s, subunit 5a; s5a
Rpn10
DESCRIPTION
Ubiquitination targets proteins for degradation by the 26S proteasome. The 26S proteasome contains a 20S catalytic core particle (see 602175) capped at either or both ends by 19S regulatory particles, which prepare substrates for hydrolysis in the core region. PSMD4 is a component of the regulatory particle that functions as a polyubiquitin receptor and captures substrates by recognizing their covalently attached ubiquitin chains (Zhang et al., 2009).CLONING
Deveraux et al. (1994) identified a 50-kD subunit of the regulatory complex of the 26S proteasome. They called this protein subunit-5 (S5) based upon its relative mobility on SDS-polyacrylamide gels. Deveraux et al. (1994) demonstrated that 2 distinct subunits of the 26S protease migrate as 50-kD proteins, and thus, S5 represents 2 proteins, which the authors termed S5A, also called PSMD4, and S5B (PSMD5; 604452). PSMD4 focuses at pH 4.6 on 2-dimensional gels. Ferrell et al. (1996) cloned a HeLa cell cDNA encoding S5A using cDNA probes based upon the sequence of Mbp1, an Arabidopsis protein physically, immunologically, and biochemically similar to S5A. The HeLa cell-derived cDNA sequence is highly similar to Mbp1 and encodes polypeptides obtained directly from human erythrocyte S5A. Expression of recombinant S5A in E. coli resulted in a protein with an apparent molecular mass matching that of the purified S5A subunit. The deduced 378-amino acid protein has a calculated molecular mass of 40.3 kD. S5A has several domains that are highly conserved between Arabidopsis, Drosophila, and Saccharomyces orthologs. A conserved 190-amino acid N-terminal domain is followed by a conserved glycine-rich region, a conserved C-terminal half containing repeated sequences, and a C terminus rich in lysine and glutamate residues (KEKE region). Using deletion analysis, Young et al. (1998) identified 2 conserved polyubiquitin-binding sites in the C-terminal half of human S5A. These sites, which the authors called PUbS1 and PUbS2, are about 30 amino acids long and are separated by a 50-amino acid linker. By PCR of an adult mouse testis cDNA library, Kawahara et al. (2000) cloned mouse Rpn10a, which encodes a protein 95% identical to human S5A. They cloned 4 other variants of mouse Rpn10, Rpn10b through Rpn10e, by PCR of embryos and embryonic stem cells. The 5 Rpn10 variants differ in the splicing of their last 4 exons, exons 7 through 10. The deduced proteins are identical in their N-terminal halves, including the PUbS1, but differ in their C-terminal halves by the presence or absence of a short insertion between PUbS1 and PUbS2 and by various C-terminal truncations. Only Rpn10a and Rpn10b contain the C-terminal KEKE region. The shortest mouse isoform, Rpn10e, is truncated following PUbS1. Kawahara et al. (2000) cloned human RPN10e by PCR of a human fetal brain cDNA library. RT-PCR detected ubiquitous expression of mouse Rpn10a, whereas Rpn10e was expressed exclusively in mouse embryos, with highest expression in embryonic brain.GENE FUNCTION
Deveraux et al. (1994) found that S5 bound ubiquitinated lysozyme as well as free polymers of ubiquitin. S5 efficiently bound to tetrameric ubiquitin and selected for longer ubiquitin polymers, a property consistent with characteristics expected of a component that selects ubiquitin conjugates for proteolysis. Deveraux et al. (1994) showed that S5A bound to ubiquitin polymers in vitro, whereas S5B did not. Ferrell et al. ... 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
Sept. 15, 2016: Protein entry updated
Automatic update: OMIM entry 601648 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed