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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. This gene encodes the largest non-ATPase subunit of the 19S regulator lid, which is responsible for substrate recognition and binding. There is evidence that this proteasome and its subunits interact with viral proteins, including those of coronaviruses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Aug 2020]
PSMD1 (Proteasome 26S Subunit, Non-ATPase 1) is a Protein Coding gene. Diseases associated with PSMD1 include Cystic Fibrosis and Bardet-Biedl Syndrome. 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 binding and enzyme regulator activity. An important paralog of this gene is PSMD2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004175 | contributes_to endopeptidase activity | IBA | 21873635 |
GO:0005515 | protein binding | IPI | 16990800 |
GO:0030234 | enzyme regulator activity | IEA | -- |
GO:0031625 | ubiquitin protein ligase binding | IPI | 16207813 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000502 | proteasome complex | IEA,IDA | 17323924 |
GO:0005576 | extracellular region | TAS | -- |
GO:0005634 | nucleus | IBA | 21873635 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005829 | cytosol | 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 | Chks in Checkpoint Regulation |
Chks in Checkpoint Regulation
.59
G2-M Phase Transition
.59
Estrogen-mediated S-Phase Entry
.55
|
SREBP Proteolysis
.43
DNA Repair Mechanisms
.32
Parkinson's Disease Pathway
.31
|
4 | HIV Life Cycle |
.64
|
.45
|
5 | Pathways of neurodegeneration - multiple diseases |
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 | |
Oprozomib | Investigational | Pharma | 0 | |||
MLN-9708 | Pharma | 0 |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PSMD1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Gm21972 31 |
|
OneToMany | |
Psmd1 30 17 31 |
|
OneToMany | |||
Oppossum (Monodelphis domestica) |
Mammalia | PSMD1 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PSMD1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PSMD1 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | PSMD1 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Psmd1 30 |
|
||
Chicken (Gallus gallus) |
Aves | PSMD1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PSMD1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | psmd1 30 |
|
||
Str.6698 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | psmd1 30 31 |
|
OneToOne | |
zgc55818 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Rpn2 30 31 32 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP001745 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | rpn-2 31 |
|
OneToOne | |
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_ACL033C 30 |
|
||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0C09284g 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | RPN2 30 31 33 |
|
OneToOne | |
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | AT1G04810 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os08g0224700 30 |
|
||
Os.15239 30 |
|
||||
Corn (Zea mays) |
Liliopsida | Zm.4098 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.3236 31 |
|
OneToOne | |
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | rpn2 30 |
|
||
Bread mold (Neurospora crassa) |
Ascomycetes | NCU09450 30 |
|
||
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.12342 30 |
|
SNP ID | Clinical significance and condition | Chr 02 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs115328679 | Benign: not provided | 231,109,129(+) |
C/T NM_000867.5(HTR2B):c.834G>A (p.Pro278=) |
SYNONYMOUS_VARIANT,INTRON | |
rs141191699 | Benign: not provided | 231,078,656(+) |
C/T NM_002807.4(PSMD1):c.1072-3C>T |
INTRON | |
rs1559236184 | Uncertain Significance: not provided | 231,113,819(+) |
T/C NM_000867.5(HTR2B):c.463A>G (p.Ile155Val) |
MISSENSE_VARIANT,INTRON | |
rs35852025 | Benign: not provided | 231,163,682(+) |
A/G NM_002807.4(PSMD1):c.2436A>G (p.Ala812=) |
NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT,INTRON | |
rs564438017 | Uncertain Significance: Bardet-Biedl syndrome | 231,109,227(+) |
T/A NM_000867.5(HTR2B):c.736A>T (p.Lys246Ter) |
NONSENSE,INTRON |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv2169n106 | CNV | deletion | 24896259 |
dgv4181n100 | CNV | loss | 25217958 |
esv1919954 | CNV | deletion | 18987734 |
esv2245776 | CNV | deletion | 18987734 |
esv2630508 | CNV | deletion | 19546169 |
esv2721610 | CNV | deletion | 23290073 |
esv3307622 | CNV | mobile element insertion | 20981092 |
esv3339619 | CNV | insertion | 20981092 |
esv3561143 | CNV | deletion | 23714750 |
esv3561144 | CNV | deletion | 23714750 |
esv4723 | CNV | loss | 18987735 |
nsv1109336 | CNV | deletion | 24896259 |
nsv1114177 | CNV | deletion | 24896259 |
nsv1148926 | CNV | deletion | 26484159 |
nsv214090 | CNV | deletion | 16902084 |
nsv511843 | CNV | loss | 21212237 |
nsv524208 | CNV | gain | 19592680 |
nsv525474 | CNV | loss | 19592680 |
Disorder | Aliases | PubMed IDs |
---|---|---|
cystic fibrosis |
|
|
bardet-biedl syndrome |
|
|