Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7PZZ4K)

• DOT Name: 26S proteasome non-ATPase regulatory subunit 7 (PSMD7)
• Synonyms: 26S proteasome regulatory subunit RPN8; 26S proteasome regulatory subunit S12; Mov34 protein homolog; Proteasome subunit p40
• Gene Name: PSMD7
• Related Disease:
  Colorectal carcinoma
  Abdominal aortic aneurysm
  Adenoma
  Advanced cancer
  Alzheimer disease
  Autoimmune disease
  Breast cancer
  Carcinoma
  Dementia
  Esophageal squamous cell carcinoma
  Ewing sarcoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Immunodeficiency
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Mycobacterium infection
  Nervous system inflammation
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Osteoarthritis
  Psoriasis
  Pulmonary disease
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Tuberculosis
  Ulcerative colitis
  Ankylosing spondylitis
  Arteriosclerosis
  Atherosclerosis
  Breast carcinoma
  HIV infectious disease
  Prostate cancer
  Prostate carcinoma
  Small-cell lung cancer
  Type-1/2 diabetes
  Malaria
  Arthritis
  Asthma
  Atopic dermatitis
  Colitis
  Neoplasm
  Type-1 diabetes
• UniProt ID: PSMD7_HUMAN
• PDB ID: 2O95 ; 2O96 ; 5GJQ ; 5GJR ; 5L4K ; 5LN3 ; 5M32 ; 5T0C ; 5T0G ; 5T0H ; 5T0I ; 5T0J ; 5VFP ; 5VFQ ; 5VFR ; 5VFS ; 5VFT ; 5VFU ; 5VGZ ; 5VHF ; 5VHH ; 5VHI ; 5VHS ; 6MSB ; 6MSD ; 6MSG ; 6MSH ; 6MSJ ; 6MSK ; 6WJD ; 6WJN ; 7QXN ; 7QXP ; 7QXU ; 7QXW ; 7QXX ; 7QY7 ; 7QYA ; 7QYB ; 7W37 ; 7W38 ; 7W39 ; 7W3A ; 7W3B ; 7W3C ; 7W3F ; 7W3G ; 7W3H ; 7W3I ; 7W3J ; 7W3K ; 7W3M ; 8CVT
• Pfam ID: PF01398 ; PF13012
• Sequence:
  MPELAVQKVVVHPLVLLSVVDHFNRIGKVGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDE
  DDKDDSVWFLDHDYLENMYGMFKKVNARERIVGWYHTGPKLHKNDIAINELMKRYCPNSV
  LVIIDVKPKDLGLPTEAYISVEEVHDDGTPTSKTFEHVTSEIGAEEAEEVGVEHLLRDIK
  DTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVATGKLPINHQIIYQLQDVFNLLPDV
  SLQEFVKAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRDAEKKEGQEKEESKKDR
  KEDKEKDKDKEKSDVKKEEKKEKK
• 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 could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.
• KEGG Pathway:
  Proteasome (hsa03050)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  ER-Phagosome pathway (R-HSA-1236974)
  Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978)
  Autodegradation of Cdh1 by Cdh1 (R-HSA-174084)
  SCF-beta-TrCP mediated degradation of Emi1 (R-HSA-174113)
  APC/C (R-HSA-174154)
  APC/C (R-HSA-174178)
  Cdc20 (R-HSA-174184)
  Vpu mediated degradation of CD4 (R-HSA-180534)
  Vif-mediated degradation of APOBEC3G (R-HSA-180585)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)
  Downstream TCR signaling (R-HSA-202424)
  Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733)
  Separation of Sister Chromatids (R-HSA-2467813)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425)
  Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)
  ABC-family proteins mediated transport (R-HSA-382556)
  AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408)
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  Degradation of AXIN (R-HSA-4641257)
  Degradation of DVL (R-HSA-4641258)
  Hedgehog ligand biogenesis (R-HSA-5358346)
  Hh mutants are degraded by ERAD (R-HSA-5362768)
  Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Degradation of GLI1 by the proteasome (R-HSA-5610780)
  Degradation of GLI2 by the proteasome (R-HSA-5610783)
  GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785)
  Hedgehog 'on' state (R-HSA-5632684)
  Regulation of RAS by GAPs (R-HSA-5658442)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)
  NIK-->noncanonical NF-kB signaling (R-HSA-5676590)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  UCH proteinases (R-HSA-5689603)
  Ub-specific processing proteases (R-HSA-5689880)
  Neutrophil degranulation (R-HSA-6798695)
  Assembly of the pre-replicative complex (R-HSA-68867)
  Orc1 removal from chromatin (R-HSA-68949)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  G2/M Checkpoints (R-HSA-69481)
  Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601)
  Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  Neddylation (R-HSA-8951664)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Interleukin-1 signaling (R-HSA-9020702)
  Negative regulation of NOTCH4 signaling (R-HSA-9604323)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  GSK3B and BTRC (R-HSA-9762114)
  Somitogenesis (R-HSA-9824272)
  Antigen processing (R-HSA-983168)
  Activation of NF-kappaB in B cells (R-HSA-1169091)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Dementia	DISXL1WY	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[13]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[18]
Mycobacterium infection	DISNSMUD	Strong	Genetic Variation	[19]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[20]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Altered Expression	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Psoriasis	DIS59VMN	Strong	Biomarker	[24]
Pulmonary disease	DIS6060I	Strong	Altered Expression	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[6]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[26]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[27]
Ankylosing spondylitis	DISRC6IR	moderate	Biomarker	[23]
Arteriosclerosis	DISK5QGC	moderate	Genetic Variation	[28]
Atherosclerosis	DISMN9J3	moderate	Genetic Variation	[28]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[29]
HIV infectious disease	DISO97HC	moderate	Genetic Variation	[30]
Prostate cancer	DISF190Y	moderate	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[4]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[31]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[28]
Malaria	DISQ9Y50	Disputed	Biomarker	[32]
Arthritis	DIST1YEL	Limited	Biomarker	[33]
Asthma	DISW9QNS	Limited	Altered Expression	[34]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[35]
Colitis	DISAF7DD	Limited	Altered Expression	[36]
Neoplasm	DISZKGEW	Limited	Biomarker	[37]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[38]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[43]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[44]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[45]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[45]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[47]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[48]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 26S proteasome non-ATPase regulatory subunit 7 (PSMD7).	[49]

References

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