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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. Two alternative transcripts encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PSMA3 (Proteasome 20S Subunit Alpha 3) is a Protein Coding gene. Diseases associated with PSMA3 include Proteasome-Associated Autoinflammatory Syndrome 1 and Cystic Fibrosis. 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 endopeptidase activity and threonine-type endopeptidase activity. An important paralog of this gene is PSMA8.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004175 | endopeptidase activity | IBA | 21873635 |
GO:0005515 | protein binding | IPI | 11146632 |
GO:0031625 | ubiquitin protein ligase binding | IPI | 16207813 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000502 | proteasome complex | IEA,IDA | 17323924 |
GO:0005634 | nucleus | IEA,TAS | 16130169 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA,TAS | 16130169 |
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:0006511 | ubiquitin-dependent protein catabolic process | IEA | -- |
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 | |
(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 | ||
Phenethyl isothiocyanate | Investigational | Pharma | Target | 12 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2 | ^ | 3a | · | 3b | ^ | 4 | ^ | 5a | · | 5b | ^ | 6a | · | 6b | · | 6c | ^ | 7 | ^ | 8 | ^ | 9a | · | 9b | ^ | 10 | ^ | 11 | ^ | 12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||||||||||||
SP3: | - | - | |||||||||||||||||||||||||||||||||||||
SP4: | - | ||||||||||||||||||||||||||||||||||||||
SP5: | |||||||||||||||||||||||||||||||||||||||
SP6: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PSMA3 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | PSMA3 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PSMA3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PSMA3 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Psma3 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Psma3 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | PSMA3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | PSMA3 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PSMA3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | psma3 30 |
|
||
Str.10919 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | psma3-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | psma3 30 31 |
|
OneToOne | |
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.6363 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Prosalpha7 30 31 32 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP001973 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | pas-7 30 31 |
|
OneToOne | |
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0A03487g 30 |
|
||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_ADR401C 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | PRE10 30 31 33 |
|
OneToOne | |
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | PAG1 30 |
|
||
Alicante grape (Vitis vinifera) |
eudicotyledons | Vvi.1689 30 |
|
||
Soybean (Glycine max) |
eudicotyledons | Gma.11323 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os01g0811100 30 |
|
||
Os.3706 30 |
|
||||
Barley (Hordeum vulgare) |
Liliopsida | Hv.2915 30 |
|
||
Wheat (Triticum aestivum) |
Liliopsida | Ta.14393 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.4861 31 |
|
OneToOne | |
Bread mold (Neurospora crassa) |
Ascomycetes | NCU02493 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | pre10 30 |
|
||
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.14529 30 |
|
SNP ID | Clinical significance and condition | Chr 14 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs1555352516 | Pathogenic: PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 1, DIGENIC | 58,258,000(+) |
T/C NM_002788.4(PSMA3):c.404+2T>C |
SPLICE_DONOR | |
rs1555353410 | Pathogenic: PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 1, DIGENIC | 58,270,970(+) |
TAAG/T NM_002788.4(PSMA3):c.697_699del (p.Arg233del) |
NON_CODING_TRANSCRIPT_VARIANT,INFRAME_DELETION |
Disorder | Aliases | PubMed IDs |
---|---|---|
proteasome-associated autoinflammatory syndrome 1 |
|
|
cystic fibrosis |
|
|
nodular episcleritis |
|
|