PSMD2 (proteasome 26S subunit ubiquitin receptor, non-ATPase 2)

Gene

• Entrez ID: 5708
• Gene name: Proteasome 26S subunit ubiquitin receptor, non-ATPase 2
• Gene symbol: PSMD2
• Synonyms (NCBI Gene): P97, RPN1, S2, TRAP2
• Chromosome: 3
• Chromosome location: 3q27.1
• 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004400	hsa-miR-200a-3p	Microarray, Northern blot	16331254
MIRT051506	hsa-let-7e-5p	CLASH	23622248
MIRT050480	hsa-miR-20a-5p	CLASH	23622248
MIRT049452	hsa-miR-92a-3p	CLASH	23622248
MIRT045290	hsa-miR-186-5p	CLASH	23622248
MIRT044106	hsa-miR-361-5p	CLASH	23622248
MIRT043381	hsa-miR-331-3p	CLASH	23622248
MIRT043028	hsa-miR-324-5p	CLASH	23622248
MIRT042898	hsa-miR-324-3p	CLASH	23622248
MIRT039985	hsa-miR-615-3p	CLASH	23622248
MIRT039985	hsa-miR-615-3p	CLASH	23622248
MIRT1270502	hsa-miR-1264	CLIP-seq
MIRT1270503	hsa-miR-1273	CLIP-seq
MIRT1270504	hsa-miR-1273c	CLIP-seq
MIRT1270505	hsa-miR-1276	CLIP-seq
MIRT1270506	hsa-miR-2278	CLIP-seq
MIRT1270507	hsa-miR-4459	CLIP-seq
MIRT1270508	hsa-miR-4695-5p	CLIP-seq
MIRT1270509	hsa-miR-4722-5p	CLIP-seq
MIRT1270510	hsa-miR-4797-3p	CLIP-seq
MIRT1270511	hsa-miR-495	CLIP-seq
MIRT1270512	hsa-miR-548n	CLIP-seq
MIRT1270513	hsa-miR-548t	CLIP-seq
MIRT1270514	hsa-miR-802	CLIP-seq
MIRT2079493	hsa-miR-1207-3p	CLIP-seq
MIRT1270503	hsa-miR-1273	CLIP-seq
MIRT1270504	hsa-miR-1273c	CLIP-seq
MIRT2079494	hsa-miR-370	CLIP-seq
MIRT1270507	hsa-miR-4459	CLIP-seq
MIRT1270508	hsa-miR-4695-5p	CLIP-seq
MIRT1270509	hsa-miR-4722-5p	CLIP-seq
MIRT2305783	hsa-miR-1184	CLIP-seq
MIRT2305784	hsa-miR-1205	CLIP-seq
MIRT1270503	hsa-miR-1273	CLIP-seq
MIRT1270504	hsa-miR-1273c	CLIP-seq
MIRT1270505	hsa-miR-1276	CLIP-seq
MIRT1270506	hsa-miR-2278	CLIP-seq
MIRT2305785	hsa-miR-3158-5p	CLIP-seq
MIRT2305786	hsa-miR-361-3p	CLIP-seq
MIRT2305787	hsa-miR-3679-3p	CLIP-seq
MIRT1270507	hsa-miR-4459	CLIP-seq
MIRT1270508	hsa-miR-4695-5p	CLIP-seq
MIRT1270509	hsa-miR-4722-5p	CLIP-seq
MIRT1270510	hsa-miR-4797-3p	CLIP-seq
MIRT1270511	hsa-miR-495	CLIP-seq
MIRT1270514	hsa-miR-802	CLIP-seq
MIRT1270510	hsa-miR-4797-3p	CLIP-seq
MIRT1270514	hsa-miR-802	CLIP-seq
MIRT1270510	hsa-miR-4797-3p	CLIP-seq
MIRT1270514	hsa-miR-802	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000502	Component	Proteasome complex	IDA	17323924
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	11278995, 16189514, 16763564, 16990800, 18457437, 18922472, 19060904, 19490896, 19615732, 22901813, 25036637, 25416956, 26496610, 27880917, 28514442, 28539385, 32296183, 32814053, 33961781, 35271311
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IBA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	TAS
GO:0005838	Component	Proteasome regulatory particle	IEA
GO:0005838	Component	Proteasome regulatory particle	TAS	8774743
GO:0008540	Component	Proteasome regulatory particle, base subcomplex	IBA
GO:0016020	Component	Membrane	HDA	19946888
GO:0022624	Component	Proteasome accessory complex	IEA
GO:0022624	Component	Proteasome accessory complex	ISS
GO:0030234	Function	Enzyme regulator activity	IEA
GO:0034515	Component	Proteasome storage granule	IBA
GO:0034774	Component	Secretory granule lumen	TAS
GO:0042176	Process	Regulation of protein catabolic process	IEA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	NAS	19489727
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:1904813	Component	Ficolin-1-rich granule lumen	TAS

Other IDs

• MIM: 606223
• HGNC: 9559
• e!Ensembl: ENSG00000175166

Protein

• UniProt ID: Q13200
• Protein name: 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2)
• 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, 5L4K, 5LN3, 5T0C, 5T0G, 5T0H, 5T0I, 5T0J, 5VFP, 5VFQ, 5VFR, 5VFS, 5VFT, 5VFU, 5VHF, 5VHH, 5VHI, 5VHJ, 5VHM, 5VHN, 5VHO, 5VHP, 5VHQ, 5VHR, 5VHS, 6MSB, 6MSD, 6MSG, 6MSH, 6MSJ, 6MSK, 6WJD, 6WJN, 7QXN, 7QXP, 7QXU, 7QXW, 7QXX, 7QY7, 7QYA, 7QYB, 7UIH, 7UJD, 7W37, 7W38, 7W39, 7W3A, 7W3B, 7W3C, 7W3F
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17781	RPN1_RPN2_N	56 → 354	RPN1/RPN2 N-terminal domain	Domain
  PF01851	PC_rep	443 → 479	Proteasome/cyclosome repeat	Repeat
  PF01851	PC_rep	480 → 514	Proteasome/cyclosome repeat	Repeat
  PF18051	RPN1_C	853 → 906	26S proteasome non-ATPase regulatory subunit RPN1 C-terminal	Domain

• Tissue specificity: TISSUE SPECIFICITY: Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta.
• Sequence:

  MEEGGRDKAPVQPQQSPAAAPGGTDEKPSGKERRDAGDKDKEQELSEEDKQLQDELEMLV
  ERLGEKDTSLYRPALEELRRQIRSSTTSMTSVPKPLKFLRPHYGKLKEIYENMAPGENKR
  FAADIISVLAMTMSGERECLKYRLVGSQEELASWGHEYVRHLAGEVAKEWQELDDAEKVQ
  REPLLTLVKEIVPYNMAHNAEHEACDLLMEIEQVDMLEKDIDENAYAKVCLYLTSCVNYV
  PEPENSALLRCALGVFRKFSRFPEALRLALMLNDMELVEDIFTSCKDVVVQKQMAFMLGR
  HGVFLELSEDVEEYEDLTEIMSNVQLNSNFLALARELDIMEPKVPDDIYKTHLENNRFGG
  SGSQVDSARMNLASSFVNGFVNAAFGQDKLLTDDGNKWLYKNKDHGMLSAAASLGMILLW
  DVDGGLTQIDKYLYSSEDYIKSGALLACGIVNSGVRNECDPALALLSDYVLHNSNTMRLG
  SIFGLGLAYAGSNREDVLTLLLPVMGDSKSSMEVAGVTALACGMIAVGSCNGDVTSTILQ
  TIMEKSETELKDTYARWLPLGLGLNHLGKGEAIEAILAALEVVSEPFRSFANTLVDVCAY
  AGSGNVLKVQQLLHICSEHFDSKEKEEDKDKKEKKDKDKKEAPADMGAHQGVAVLGIALI
  AMGEEIGAEMALRTFGHLLRYGEPTLRRAVPLALALISVSNPRLNILDTLSKFSHDADPE
  VSYNSIFAMGMVGSGTNNARLAAMLRQLAQYHAKDPNNLFMVRLAQGLTHLGKGTLTLCP
  YHSDRQLMSQVAVAGLLTVLVSFLDVRNIILGKSHYVLYGLVAAMQPRMLVTFDEELRPL
  PVSVRVGQAVDVVGQAGKPKTITGFQTHTTPVLLAHGERAELATEEFLPVTPILEGFVIL
  RKNPNYDL

• Sequence length: 908

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Adenocarcinoma of Lung	Associate	23874428	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	29328377	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Stimulate	34839279	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Associate	31703613, 36292719	★☆☆☆☆ Found in Text Mining only
Carcinoma Non Small Cell Lung	Associate	37864031	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	35173535	★☆☆☆☆ Found in Text Mining only
Depressive Disorder Major	Associate	31305436	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Associate	28253288	★☆☆☆☆ Found in Text Mining only
Heat Stress Disorders	Associate	25280538	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Associate	25734857	★☆☆☆☆ Found in Text Mining only
Liver Failure	Associate	25280538	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Associate	37875476	★☆☆☆☆ Found in Text Mining only
Neoplasm Metastasis	Associate	23874428	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	31703613, 34398824, 36123629	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Associate	37349676	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Associate	34398824	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Associate	31136974	★☆☆☆☆ Found in Text Mining only
Thyroiditis	Associate	28390009	★☆☆☆☆ Found in Text Mining only