PSMC3 (proteasome 26S subunit, ATPase 3)

Gene

• Entrez ID: 5702
• Gene name: Proteasome 26S subunit, ATPase 3
• Gene symbol: PSMC3
• Synonyms (NCBI Gene): DCIDP, RPT5, TBP1
• Chromosome: 11
• Chromosome location: 11p11.2
• Summary: 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 a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1177898071	T>C,G	Pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050417	hsa-miR-23a-3p	CLASH	23622248
MIRT049107	hsa-miR-92a-3p	CLASH	23622248
MIRT049107	hsa-miR-92a-3p	CLASH	23622248
MIRT048151	hsa-miR-196a-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000502	Component	Proteasome complex	IDA	9464850, 17323924
GO:0000502	Component	Proteasome complex	IEA
GO:0000502	Component	Proteasome complex	NAS	29636472
GO:0000502	Component	Proteasome complex	TAS	8811196
GO:0000932	Component	P-body	IEA
GO:0000932	Component	P-body	ISS
GO:0001824	Process	Blastocyst development	IEA
GO:0005515	Function	Protein binding	IPI	16713569, 16763564, 16990800, 19490896, 24255178, 25416956, 27342858, 28514442, 29636472, 31515488, 32296183, 32814053, 33961781, 35271311
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IDA	2194290
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0008540	Component	Proteasome regulatory particle, base subcomplex	IBA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0022624	Component	Proteasome accessory complex	IEA
GO:0022624	Component	Proteasome accessory complex	ISS
GO:0034774	Component	Secretory granule lumen	TAS
GO:0036402	Function	Proteasome-activating activity	IBA
GO:0036402	Function	Proteasome-activating activity	ISS	1429620
GO:0036402	Function	Proteasome-activating activity	TAS	9464850
GO:0042802	Function	Identical protein binding	IPI	25416956, 32296183
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	NAS	19489727
GO:0043921	Process	Host-mediated perturbation of viral transcription	IDA	2194290, 8419915
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	19853614
GO:1901800	Process	Positive regulation of proteasomal protein catabolic process	IC	9464850
GO:1904813	Component	Ficolin-1-rich granule lumen	TAS

Other IDs

• MIM: 186852
• HGNC: 9549
• e!Ensembl: ENSG00000165916

Protein

• UniProt ID: P17980
• Protein name: 26S proteasome regulatory subunit 6A (26S proteasome AAA-ATPase subunit RPT5) (Proteasome 26S subunit ATPase 3) (Proteasome subunit P50) (Tat-binding protein 1) (TBP-1)
• Protein function: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which
• PDB: 5GJQ, 5GJR, 5L4G, 5LN3, 5M32, 5T0C, 5T0G, 5T0H, 5T0I, 5T0J, 5VFP, 5VFQ, 5VFR, 5VFS, 5VFT, 5VFU, 5VGZ, 5VHF, 5VHH, 5VHI, 5VHJ, 5VHM, 5VHN, 5VHO, 5VHP, 5VHQ, 5VHR, 5VHS, 6MSB, 6MSD, 6MSE, 6MSG, 6MSH, 6MSJ, 6MSK, 6WJD, 6WJN, 7QXN, 7QXP, 7QXU, 7QXW, 7QXX, 7QY7, 7QYA, 7QYB, 7W37, 7W38, 7W39, 7W3A, 7W3B, 7W3C
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16450	Prot_ATP_ID_OB	90 → 165	Proteasomal ATPase OB C-terminal domain	Domain
  PF00004	AAA	223 → 356	ATPase family associated with various cellular activities (AAA)	Domain
  PF17862	AAA_lid_3	378 → 422	AAA+ lid domain	Domain

• Sequence:

  MNLLPNIESPVTRQEKMATVWDEAEQDGIGEEVLKMSTEEIIQRTRLLDSEIKIMKSEVL
  RVTHELQAMKDKIKENSEKIKVNKTLPYLVSNVIELLDVDPNDQEEDGANIDLDSQRKGK
  CAVIKTSTRQTYFLPVIGLVDAEKLKPGDLVGVNKDSYLILETLPTEYDSRVKAMEVDER
  PTEQYSDIGGLDKQIQELVEAIVLPMNHKEKFENLGIQPPKGVLMYGPPGTGKTLLARAC
  AAQTKATFLKLAGPQLVQMFIGDGAKLVRDAFALAKEKAPSIIFIDELDAIGTKRFDSEK
  AGDREVQRTMLELLNQLDGFQPNTQVKVIAATNRVDILDPALLRSGRLDRKIEFPMPNEE
  ARARIMQIHSRKMNVSPDVNYEELARCTDDFNGAQCKAVCVEAGMIALRRGATELTHEDY
  MEGILEVQAKKKANLQYYA

• Sequence length: 439

Pathways

KEGG:

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

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
Neutrophil degranulation
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
Deafness, cataract, impaired intellectual development, and polyneuropathy	Pathogenic	rs1177898071	RCV001450093	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Developmental cataract	Pathogenic	rs1177898071	RCV000768461	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental delay	Pathogenic	rs1177898071	RCV000768461	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe sensorineural hearing impairment	Pathogenic	rs1177898071	RCV000768461	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOMALOUS PULMONARY VEIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CATARACT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HIV INFECTIONS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PATENT DUCTUS ARTERIOSUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYMICROGYRIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Breast Neoplasms	Associate	34329194	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Associate	12733146	★☆☆☆☆ Found in Text Mining only
Carcinoma Non Small Cell Lung	Inhibit	32386284	★☆☆☆☆ Found in Text Mining only
Hepatitis B	Associate	35695579	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Inhibit	32386284	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	12733146, 32386284	★☆☆☆☆ Found in Text Mining only