26S proteasome non-ATPase regulatory subunit 11 (PSMD11)

The protein contains 422 amino acids for an estimated molecular weight of 47464 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. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity. (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 71

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Biological Process

Anaphase-promoting complex-dependent catabolic process GO Logo
Antigen processing and presentation of exogenous peptide antigen via MHC class I GO Logo
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent GO Logo
Antigen processing and presentation of peptide antigen via MHC class I GO Logo
Apoptotic process GO Logo
Cellular nitrogen compound metabolic process GO Logo
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO Logo
Fc-epsilon receptor signaling pathway GO Logo
G1/S transition of mitotic cell cycle GO Logo
Gene expression GO Logo
Interleukin-1-mediated signaling pathway GO Logo
MAPK cascade GO Logo
Mitotic cell cycle GO Logo
Negative regulation of apoptotic process GO Logo
Negative regulation of canonical Wnt signaling pathway GO Logo
Negative regulation of G2/M transition of mitotic cell cycle GO Logo
Neutrophil degranulation GO Logo
NIK/NF-kappaB signaling GO Logo
Obsolete negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle GO Logo
Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition GO Logo
Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle GO Logo
Positive regulation of canonical Wnt signaling pathway GO Logo
Post-translational protein modification GO Logo
Pre-replicative complex assembly GO Logo
Proteasome assembly GO Logo
Proteasome-mediated ubiquitin-dependent protein catabolic process GO Logo
Protein deubiquitination GO Logo
Protein polyubiquitination GO Logo
Regulation of apoptotic process GO Logo
Regulation of cellular amino acid metabolic process GO Logo
Regulation of hematopoietic stem cell differentiation GO Logo
Regulation of mitotic cell cycle phase transition GO Logo
Regulation of mRNA stability GO Logo
Regulation of transcription from RNA polymerase II promoter in response to hypoxia GO Logo
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO Logo
Small molecule metabolic process GO Logo
Stem cell differentiation GO Logo
Stimulatory C-type lectin receptor signaling pathway GO Logo
T cell receptor signaling pathway GO Logo
Transmembrane transport GO Logo
Tumor necrosis factor-mediated signaling pathway GO Logo
Ubiquitin-dependent protein catabolic process GO Logo
Viral process GO Logo
Wnt signaling pathway, planar cell polarity pathway GO Logo

Molecular Function

Structural molecule activity GO Logo

The reference OMIM entry for this protein is 604449

Proteasome 26s subunit, non-atpase, 11; psmd11
Protease 26s, subunit 9; s9
P44.5

DESCRIPTION

The PSMD11 gene encodes a non-ATPase subunit of the PA700 regulatory subcomplex of the 26S proteasome. The 26S proteasome is responsible for the ATP-dependent degradation of a variety of cellular proteins. Selective breakdown of these proteins is mediated by the ubiquitin pathway. The 26S proteasome is a 2,000-kD protein complex composed of the 20S proteasome, which is the catalytic subcomplex, and PA700, which is the regulatory subcomplex. The approximately 700-kD PA700 complex consists of approximately 20 heterogeneous proteins ranging from 25 to 112 kD. These subunits can be divided into 2 classes, those that are members of the AAA (ATPases associated with various cellular activities) family and those that are not (summary by Hoffman and Rechsteiner, 1997, Saito et al., 1997).

CLONING

Hoffman and Rechsteiner (1997) sequenced peptides from subunit 9 of the human 26S proteasome. Using the amino acid sequences, they cloned HeLa cell cDNAs encoding subunit 9, also called PSMD11. The predicted 422-amino acid protein has 9 dileucine repeats, possible coiled-coil domains, and potential myristylation and phosphorylation sites. PSMD11 is not a member of the ATPase family. Whereas the calculated molecular mass of PSMD11 is 47,469 Da, it migrates as an approximately 46-kD protein on SDS-polyacrylamide gels. Saito et al. (1997) sequenced peptides from the p44.5 subunit of the bovine PA700 complex. They identified human ESTs encoding homologous proteins and used these ESTs to isolate hepatoblastoma HepG2 cell cDNAs encoding human p44.5. The authors stated that the p44.5 subunit is equivalent to subunit 9 (Hoffman and Rechsteiner, 1997), or PSMD11. Saito et al. (1997) identified a putative S. cerevisiae homolog, which they named NAS4, that shares 45.4% amino acid sequence identity with PSMD11. Disruption of the NAS4 gene resulted in lethality.

GENE FUNCTION

Vilchez et al. (2012) demonstrated that human embryonic stem cells exhibit high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11 and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. FOXO4 (300033), an insulin/insulin-like growth factor-I (IGF1; 147440)-responsive transcription factor associated with long life span in invertebrates, regulates proteasome activity by modulating the expression of PSMD11 in human embryonic stem cells. Proteasome inhibition in human embryonic stem cells affects the expression of pluripotency markers and the levels of specific markers of the distinct germ layers. Vilchez et al. (2012) concluded that their results suggested a new regulation of proteostasis in human embryonic stem cells that links longevity and stress resistance in invertebrates to human embryonic stem cell function and identity.

MAPPING

Gross (2014) mapped the PSMD11 gene to chromosome 17q11.2 based on an alignment of the PSMD11 sequence (GenBank GENBANK AB003102) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 604449 was added.