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The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the gamma subunit of the 11S regulator. Six gamma subunits combine to form a homohexameric ring. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
PSME3 (Proteasome Activator Subunit 3) is a Protein Coding gene. Diseases associated with PSME3 include Systemic Lupus Erythematosus. Among its related pathways are Downstream signaling events of B Cell Receptor (BCR) and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include identical protein binding and MDM2/MDM4 family protein binding. An important paralog of this gene is PSME1.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002039 | p53 binding | IDA | 18309296 |
GO:0005515 | protein binding | IPI | 12970408 |
GO:0042802 | identical protein binding | IPI | 16169070 |
GO:0061133 | endopeptidase activator activity | IBA,IDA | 18309296 |
GO:0097371 | MDM2/MDM4 family protein binding | IDA | 18309296 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000502 | proteasome complex | IEA,TAS | 8811196 |
GO:0005634 | nucleus | IEA,HDA | 21630459 |
GO:0005654 | nucleoplasm | IDA,TAS | -- |
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005829 | cytosol | IDA,TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | CDK-mediated phosphorylation and removal of Cdc6 |
.93
.93
|
.80
.80
.78
.70
.47
.31
|
2 | RET signaling |
.92
|
.92
|
3 | HIV Life Cycle |
.64
|
.45
|
4 | Class I MHC mediated antigen processing and presentation | ||
5 | Antigen processing-Cross presentation |
Immune response Antigen presentation by MHC class I
.51
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000209 | protein polyubiquitination | TAS | -- |
GO:0002223 | stimulatory C-type lectin receptor signaling pathway | TAS | -- |
GO:0002479 | antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent | TAS | -- |
GO:0006521 | regulation of cellular amino acid metabolic process | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Bortezomib | Approved, Investigational | Pharma | inhibitor, other | Proteosome and NF-kappaB inhibitor, Other, Proteasome inhibitors | 926 | |
carfilzomib | Approved, Investigational | Pharma | other, Inhibitor | Other, 20S Proteasome Inhibitor | 0 | |
AM 114 | Pharma | 20S proteasome inhibitor | 0 | |||
CEP-18770 | Pharma | Proteasome inhibitor | 0 | |||
MLN9708 | Pharma | Proteasome inhibitor, 20S Proteasome Inhibitor | 0 |