PSMA3 (proteasome 20S subunit alpha 3)

Gene

• Entrez ID: 5684
• Gene name: Proteasome 20S subunit alpha 3
• Gene symbol: PSMA3
• Synonyms (NCBI Gene): HC8, PSC3
• Chromosome: 14
• Chromosome location: 14q23.1
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1555352516	T>C	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050117	hsa-miR-26a-5p	CLASH	23622248
MIRT044295	hsa-miR-106b-5p	CLASH	23622248
MIRT043928	hsa-miR-378a-3p	CLASH	23622248
MIRT042723	hsa-miR-346	CLASH	23622248
MIRT054213	hsa-miR-147a	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23028679
MIRT1269983	hsa-miR-1269	CLIP-seq
MIRT1269984	hsa-miR-1269b	CLIP-seq
MIRT1269985	hsa-miR-1287	CLIP-seq
MIRT1269986	hsa-miR-1288	CLIP-seq
MIRT1269987	hsa-miR-144	CLIP-seq
MIRT1269988	hsa-miR-3121-3p	CLIP-seq
MIRT1269989	hsa-miR-3135b	CLIP-seq
MIRT1269990	hsa-miR-338-5p	CLIP-seq
MIRT1269991	hsa-miR-3647-3p	CLIP-seq
MIRT1269992	hsa-miR-3924	CLIP-seq
MIRT1269993	hsa-miR-4515	CLIP-seq
MIRT1269994	hsa-miR-4520a-3p	CLIP-seq
MIRT1269995	hsa-miR-4520b-3p	CLIP-seq
MIRT1269996	hsa-miR-4529-3p	CLIP-seq
MIRT1269997	hsa-miR-4645-3p	CLIP-seq
MIRT1269998	hsa-miR-4666-3p	CLIP-seq
MIRT1269999	hsa-miR-4685-5p	CLIP-seq
MIRT1270000	hsa-miR-4740-5p	CLIP-seq
MIRT1270001	hsa-miR-568	CLIP-seq
MIRT1269987	hsa-miR-144	CLIP-seq
MIRT1269988	hsa-miR-3121-3p	CLIP-seq
MIRT1269992	hsa-miR-3924	CLIP-seq
MIRT1269994	hsa-miR-4520a-3p	CLIP-seq
MIRT1269995	hsa-miR-4520b-3p	CLIP-seq
MIRT1269997	hsa-miR-4645-3p	CLIP-seq
MIRT1269999	hsa-miR-4685-5p	CLIP-seq
MIRT1270001	hsa-miR-568	CLIP-seq
MIRT1269983	hsa-miR-1269	CLIP-seq
MIRT1269984	hsa-miR-1269b	CLIP-seq
MIRT1269985	hsa-miR-1287	CLIP-seq
MIRT1269986	hsa-miR-1288	CLIP-seq
MIRT1269987	hsa-miR-144	CLIP-seq
MIRT1269988	hsa-miR-3121-3p	CLIP-seq
MIRT1269989	hsa-miR-3135b	CLIP-seq
MIRT1269990	hsa-miR-338-5p	CLIP-seq
MIRT1269992	hsa-miR-3924	CLIP-seq
MIRT1269993	hsa-miR-4515	CLIP-seq
MIRT1269994	hsa-miR-4520a-3p	CLIP-seq
MIRT1269995	hsa-miR-4520b-3p	CLIP-seq
MIRT1269996	hsa-miR-4529-3p	CLIP-seq
MIRT1269997	hsa-miR-4645-3p	CLIP-seq
MIRT1269998	hsa-miR-4666-3p	CLIP-seq
MIRT1269999	hsa-miR-4685-5p	CLIP-seq
MIRT1270000	hsa-miR-4740-5p	CLIP-seq
MIRT1270001	hsa-miR-568	CLIP-seq
MIRT1269983	hsa-miR-1269	CLIP-seq
MIRT1269984	hsa-miR-1269b	CLIP-seq
MIRT1269986	hsa-miR-1288	CLIP-seq
MIRT1269987	hsa-miR-144	CLIP-seq
MIRT1269988	hsa-miR-3121-3p	CLIP-seq
MIRT1269992	hsa-miR-3924	CLIP-seq
MIRT1269993	hsa-miR-4515	CLIP-seq
MIRT1269994	hsa-miR-4520a-3p	CLIP-seq
MIRT1269995	hsa-miR-4520b-3p	CLIP-seq
MIRT1269996	hsa-miR-4529-3p	CLIP-seq
MIRT1269997	hsa-miR-4645-3p	CLIP-seq
MIRT1269999	hsa-miR-4685-5p	CLIP-seq
MIRT1270000	hsa-miR-4740-5p	CLIP-seq
MIRT1270001	hsa-miR-568	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000502	Component	Proteasome complex	IDA	17323924, 26524591
GO:0000502	Component	Proteasome complex	IEA
GO:0000502	Component	Proteasome complex	NAS	29636472
GO:0000502	Component	Proteasome complex	TAS	8811196
GO:0005515	Function	Protein binding	IPI	11146632, 12376572, 12826010, 14733938, 15225636, 16169070, 17948026, 19208651, 21516116, 21900206, 21988832, 22659184, 24722188, 25416956, 25599644, 25910212, 26871637, 29568061, 29636472, 29892012, 31473102, 31515488, 32296183, 32814053, 33961781, 34702852, 35271311, 35858375
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	34711951
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	16130169
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	34711951
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	16130169
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005839	Component	Proteasome core complex	IDA	19208651, 34711951
GO:0005839	Component	Proteasome core complex	IEA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IEA
GO:0019773	Component	Proteasome core complex, alpha-subunit complex	IBA
GO:0019773	Component	Proteasome core complex, alpha-subunit complex	IEA
GO:0019773	Component	Proteasome core complex, alpha-subunit complex	ISS
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	16207813
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IMP	26524591
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	NAS	19489727
GO:0051603	Process	Proteolysis involved in protein catabolic process	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337

Other IDs

• MIM: 176843
• HGNC: 9532
• e!Ensembl: ENSG00000100567

Protein

• UniProt ID: P25788
• Protein name: Proteasome subunit alpha type-3 (Macropain subunit C8) (Multicatalytic endopeptidase complex subunit C8) (Proteasome component C8) (Proteasome subunit alpha-7) (alpha-7)
• Protein function: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with
• PDB: 4R3O, 4R67, 5A0Q, 5DSV, 5GJQ, 5GJR, 5L4G, 5LE5, 5LEX, 5LEY, 5LEZ, 5LF0, 5LF1, 5LF3, 5LF4, 5LF6, 5LF7, 5LN3, 5M32, 5T0C, 5T0G, 5T0H, 5T0I, 5T0J, 5VFO, 5VFP, 5VFQ, 5VFR, 5VFS, 5VFT, 5VFU, 6AVO, 6E5B, 6KWY, 6MSB, 6MSD, 6MSE, 6MSG, 6MSH, 6MSJ, 6MSK, 6R70, 6REY, 6RGQ, 6WJD, 6WJN, 6XMJ, 7AWE, 7B12, 7E55, 7LXV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10584	Proteasome_A_N	8 → 30	Proteasome subunit A N-terminal signature	Family
  PF00227	Proteasome	31 → 217	Proteasome subunit	Domain

• Sequence:

  MSSIGTGYDLSASTFSPDGRVFQVEYAMKAVENSSTAIGIRCKDGVVFGVEKLVLSKLYE
  EGSNKRLFNVDRHVGMAVAGLLADARSLADIAREEASNFRSNFGYNIPLKHLADRVAMYV
  HAYTLYSAVRPFGCSFMLGSYSVNDGAQLYMIDPSGVSYGYWGCAIGKARQAAKTEIEKL
  QMKEMTCRDIVKEVAKIIYIVHDEVKDKAFELELSWVGELTNGRHEIVPKDIREEAEKYA
  KESLKEEDESDDDNM

• Sequence length: 255

Pathways

KEGG:

Proteasome
Alzheimer disease
Parkinson disease
Amyotrophic lateral sclerosis
Huntington disease
Spinocerebellar ataxia
Prion disease
Pathways of neurodegeneration - multiple diseases

Reactome:

Activation of NF-kappaB in B cells
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
Cross-presentation of soluble exogenous antigens (endosomes)
Autodegradation of Cdh1 by Cdh1:APC/C
SCF-beta-TrCP mediated degradation of Emi1
APC/C:Cdc20 mediated degradation of Securin
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
Cdc20:Phospho-APC/C mediated degradation of Cyclin A
Vpu mediated degradation of CD4
Vif-mediated degradation of APOBEC3G
SCF(Skp2)-mediated degradation of p27/p21
Degradation of beta-catenin by the destruction complex
Downstream TCR signaling
Separation of Sister Chromatids
FCERI mediated NF-kB activation
Autodegradation of the E3 ubiquitin ligase COP1
Regulation of ornithine decarboxylase (ODC)
ABC-family proteins mediated transport
AUF1 (hnRNP D0) binds and destabilizes mRNA
Asymmetric localization of PCP proteins
Degradation of AXIN
Degradation of DVL
Hedgehog ligand biogenesis
Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
Dectin-1 mediated noncanonical NF-kB signaling
CLEC7A (Dectin-1) signaling
Degradation of GLI1 by the proteasome
GLI3 is processed to GLI3R by the proteasome
Hedgehog 'on' state
Regulation of RAS by GAPs
TNFR2 non-canonical NF-kB pathway
NIK-->noncanonical NF-kB signaling
Defective CFTR causes cystic fibrosis
MAPK6/MAPK4 signaling
UCH proteinases
Ub-specific processing proteases
CDT1 association with the CDC6:ORC:origin complex
Orc1 removal from chromatin
CDK-mediated phosphorylation and removal of Cdc6
G2/M Checkpoints
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
Ubiquitin-dependent degradation of Cyclin D
The role of GTSE1 in G2/M progression after G2 checkpoint
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
RUNX1 regulates transcription of genes involved in differentiation of HSCs
Regulation of RUNX2 expression and activity
Regulation of RUNX3 expression and activity
Regulation of PTEN stability and activity
Neddylation
Interleukin-1 signaling
Antigen processing: Ubiquitination & Proteasome degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 1, DIGENIC	Pathogenic	rs1555353410, rs1555352516	RCV000663431 RCV000663432	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSMA3-related disorder	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Adenocarcinoma	Associate	38203269	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Associate	36405716	★☆☆☆☆ Found in Text Mining only
Arthritis	Associate	24875235	★☆☆☆☆ Found in Text Mining only
Arthritis Juvenile	Associate	24875235, 30940621	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	28990063	★☆☆☆☆ Found in Text Mining only
Carcinoma Non Small Cell Lung	Associate	34610219	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Stimulate	35022330, 36144640	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	33275226	★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Associate	32005028	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Associate	32005028, 34755333	★☆☆☆☆ Found in Text Mining only
Glioma	Stimulate	34294084	★☆☆☆☆ Found in Text Mining only
Inflammation	Stimulate	34516337	★☆☆☆☆ Found in Text Mining only
Inflammation	Associate	34755333	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Associate	37088992	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Associate	34610219	★☆☆☆☆ Found in Text Mining only
Myopathy with Lactic Acidosis Hereditary	Associate	35178454	★☆☆☆☆ Found in Text Mining only
Neoplasm Metastasis	Associate	34720049	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	34294084, 35022330, 35178454, 37088992	★☆☆☆☆ Found in Text Mining only
Neoplasms Squamous Cell	Associate	34755333	★☆☆☆☆ Found in Text Mining only
Obesity	Associate	24455213	★☆☆☆☆ Found in Text Mining only
Ossification Heterotopic	Associate	33391181	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Inhibit	34755333	★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Stimulate	34284720	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Associate	34457087	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stimulate	27966459	★☆☆☆☆ Found in Text Mining only
Tertiary Lymphoid Structures	Stimulate	35022330	★☆☆☆☆ Found in Text Mining only
Thyroiditis	Associate	28390009	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Associate	34720049, 35669725	★☆☆☆☆ Found in Text Mining only