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The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 a member of the peptidase T1A family, that is a 20S core alpha subunit. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]
PSMA1 (Proteasome 20S Subunit Alpha 1) is a Protein Coding gene. Diseases associated with PSMA1 include Cystic Fibrosis and Alzheimer Disease. Among its related pathways are Regulation of activated PAK-2p34 by proteasome mediated degradation and Antigen processing-Cross presentation. Gene Ontology (GO) annotations related to this gene include RNA binding and threonine-type endopeptidase activity. An important paralog of this gene is ENSG00000256206.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001530 | lipopolysaccharide binding | IEA | -- |
GO:0003723 | RNA binding | TAS | 7681138 |
GO:0004175 | endopeptidase activity | IBA | 21873635 |
GO:0004298 | threonine-type endopeptidase activity | IEA | -- |
GO:0005515 | protein binding | IPI | 12376572 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000502 | proteasome complex | TAS,IDA | 17323924 |
GO:0005634 | nucleus | TAS,IBA | 21873635 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005813 | centrosome | IDA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Regulation of activated PAK-2p34 by proteasome mediated degradation |
.93
.93
|
.80
.79
.78
.69
.47
|
2 | RET signaling |
.92
|
.92
|
3 | Chks in Checkpoint Regulation |
Chks in Checkpoint Regulation
.58
G2-M Phase Transition
.58
Estrogen-mediated S-Phase Entry
.54
|
SREBP Proteolysis
.42
DNA Repair Mechanisms
.31
Parkinson's Disease Pathway
.30
|
4 | HIV Life Cycle |
.65
|
.45
|
5 | Parkinson disease |
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:0002376 | immune system process | IEA | -- |
GO:0002479 | antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent | 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 | 910 | |
carfilzomib | Approved, Investigational | Pharma | other, Inhibitor | Other, 20S Proteasome Inhibitor | 0 | |
(3AR,6R,6AS)-6-((S)-((S)-CYCLOHEX-2-ENYL)(HYDROXY)METHYL)-6A-METHYL-4-OXO-HEXAHYDRO-2H-FURO[3,2-C]PYRROLE-6-CARBALDEHYDE | Experimental | Pharma | Target | 0 | ||
AM 114 | Pharma | 20S proteasome inhibitor | 0 | |||
Bortezomib (PS-341) | Pharma | Proteasome Inhibitor | 0 |
Compound | Action | Cas Number |
---|---|---|
AM 114 | 20S proteasome inhibitor | 856849-35-9 |
Bortezomib (PS-341) | Proteasome Inhibitor | 179324-69-7 |
Carfilzomib (PR-171) | Proteasome inhibitor,epoxomicin analog | 868540-17-4 |
Celastrol | Antioxidant, anti-inflammatory and immunosuppressive agent | 34157-83-0 |
CEP-18770 | Proteasome inhibitor | 847499-27-8 |
Dihydroeponemycin | Proteasome inhibitor,antitumor reagent,eponemycin ddrivative | 126463-64-7 |
Epoxomicin | Proteasome inhibitor | 134381-21-8 |
MG-132 | Proteasome inhibitor, Cell permeable, reversible | 133407-82-6 |
MLN2238 | β5 site of the 20S proteasome inhibitor | 1072833-77-2 |
MLN9708 | Proteasome inhibitor | 1201902-80-8 |
ONX-0914 (PR-957) | Immunoproteasome inhibitor,potent and selective | 960374-59-8 |
Oprozomib (ONX-0912) | Proteasome inhibitor | 935888-69-0 |
PI-1840 | Chymotrypsin-like (CT-L) inhibitor | 1401223-22-0 |
PSI | Proteasome inhibitor | 158442-41-2 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2a | · | 2b | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6a | · | 6b | · | 6c | ^ | 7a | · | 7b | ^ | 8a | · | 8b | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12a | · | 12b | · | 12c |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||
SP4: | |||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP6: | |||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PSMA1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
PSMA1 30 |
|
||||
-- 31 |
|
ManyToMany | |||
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
Cow (Bos Taurus) |
Mammalia | PSMA1 30 31 |
|
OneToMany | |
Mouse (Mus musculus) |
Mammalia | Psma1 30 17 31 |
|
OneToMany | |
Rat (Rattus norvegicus) |
Mammalia | Psma1 30 |
|
||
Chicken (Gallus gallus) |
Aves | PSMA1 30 31 |
|
OneToMany | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
OneToMany | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | Str.5957 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | psma1 30 31 |
|
OneToMany | |
wufc17c09 30 |
|
||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.8498 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Prosalpha6T 30 31 32 |
|
ManyToMany | |
Pros35 31 32 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | pas-6 30 31 |
|
OneToMany | |
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | PRE5 30 31 |
|
OneToMany | |
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0A10153g 30 |
|
||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AGL336W 30 |
|
||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | PAF2 30 |
|
||
Alicante grape (Vitis vinifera) |
eudicotyledons | Vvi.6955 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os02g0133800 30 |
|
||
Barley (Hordeum vulgare) |
Liliopsida | Hv.2240 30 |
|
||
Wheat (Triticum aestivum) |
Liliopsida | Ta.18932 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.5765 31 |
|
OneToMany | |
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | SPAC6G10.04c 30 |
|
||
Bread mold (Neurospora crassa) |
Ascomycetes | NCU06712 30 |
|
||
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.4798 30 |
|
SNP ID | Clinical significance and condition | Chr 11 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
716419 | Benign: not provided | 14,507,704(-) | C/T | SYNONYMOUS_VARIANT | |
784186 | Likely Benign: not provided | 14,519,042(-) | CTAAAAG/C | SPLICE_ACCEPTOR_VARIANT | |
rs17850016 | - | p.Gly37Val |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3305305 | CNV | mobile element insertion | 20981092 |
esv3324169 | CNV | insertion | 20981092 |
esv3578250 | CNV | gain | 25503493 |
esv3625423 | CNV | loss | 21293372 |
esv3625424 | CNV | loss | 21293372 |
nsv1048243 | CNV | gain | 25217958 |
nsv517985 | CNV | loss | 19592680 |
nsv518508 | CNV | loss | 19592680 |
nsv7685 | CNV | insertion | 18451855 |
nsv951312 | CNV | deletion | 24416366 |
Disorder | Aliases | PubMed IDs |
---|---|---|
cystic fibrosis |
|
|
alzheimer disease |
|
|
lung cancer |
|
|
breast cancer |
|
|