26S proteasome regulatory subunit 6A (PSMC3)
The protein contains 439 amino acids for an estimated molecular weight of 49204 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. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. (updated: Dec. 20, 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.
- 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
Blastocyst development
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
Modulation by host of viral transcription
Negative regulation of apoptotic process
Negative regulation of canonical Wnt signaling pathway
Negative regulation of G2/M transition of mitotic cell cycle
Negative regulation of nucleic acid-templated transcription
Neutrophil degranulation
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 RNA polymerase II transcription preinitiation complex assembly
Positive regulation of transcription by RNA polymerase II
Post-translational protein modification
Pre-replicative complex 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 nucleic acid-templated transcription
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
Ubiquitin-dependent ERAD pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
Cellular Component
Cytosol
Cytosolic proteasome complex
Extracellular region
Ficolin-1-rich granule lumen
Membrane
Nuclear proteasome complex
Nucleoplasm
Nucleus
P-body
Perinuclear region of cytoplasm
Proteasome accessory complex
Proteasome complex
Proteasome regulatory particle, base subcomplex
Secretory granule lumen
The reference OMIM entry for this protein is 186852
Proteasome 26s subunit, atpase, 3; psmc3
Tat-binding protein 1; tbp1
CLONING
The human immunodeficiency virus-1 (HIV-1) protein Tat is a potent activator of virus gene expression and replication. Nelbock et al. (1990) used biotinylated Tat as a probe to screen a lambda-gt11 fusion protein library, thereby cloning a cDNA encoding a protein that interacts with Tat. Expression of this protein, designated Tat-binding protein-1, was observed in a variety of cell lines, with expression being highest in human cells. TBP1 was localized predominantly in the nucleus, which is consistent with the nuclear localization of Tat. In cotransfection experiments, expression of TBP1 was able to suppress Tat-mediated transactivation specifically. Nelbock et al. (1990) recommended their strategy for direct identification and cloning of genes encoding proteins that associate with other proteins to modulate their activity in a positive or negative fashion. Ohana et al. (1993) suggested that TBP1 is involved in Tat-mediated transcriptional activation.GENE FUNCTION
Ubiquitinated proteins are degraded by a 26S ATP-dependent protease. The protease is composed of a 20S catalytic proteasome and 2 PA700 regulatory modules (see PSMC1; 602706). DeMartino et al. (1996) identified a protein complex that enhances PA700 activation of the proteasome. They found that 2 proteins, p42 (PSMC6; 602708) and p50 (PSMC3), are components of both this complex and PA700. By protein sequence analysis, DeMartino et al. (1996) determined that p50 and TBP1 are identical. Hoyle et al. (1997) stated that the PSMC3 gene encodes a protein with 1 AAA (ATPases associated with diverse cellular activities) domain (see PSMC5; 601681) toward the C terminus. Corn et al. (2003) established that pVHL (608537), the protein that is mutant in von Hippel-Lindau syndrome (193300), binds to TBP1. TBP1 associates with the beta-domain of pVHL and complexes with pVHL and hypoxia-inducible transcription factor HIF1A (603348) in vivo. Overexpression of TBP1 promotes degradation of HIF1A in a pVHL-dependent manner that requires the ATPase domain of TBP1. Several distinct mutations in exon 2 of the VHL gene disrupt binding of pVHL to TBP1. A pVHL mutant containing an exon 2 missense substitution coimmunoprecipitated with HIF1A, but not TBP1, and did not promote degradation of HIF1A. Thus, the ability of pVHL to degrade HIF1A depends in part on its interaction with TBP1 and suggests a new mechanism for HIF1A stabilization in some pVHL-deficient tumors.MAPPING
By PCR amplification of a partial PSMC3 sequence, Hoyle et al. (1997) demonstrated that the PSMC3 gene is located on chromosome 11. By fluorescence in situ hybridization (FISH), the assignment was regionalized to 11p13-p12. Tanahashi et al. (1998) mapped the PSMC3 gene to 11p11.2 by FISH. By interspecific backcross analysis, Sakao et al. (2000) mapped the mouse Psmc3 gene to chromosome 2. ... 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 186852 was added.