Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ5I6UM)

DOT Name Proteasome assembly chaperone 1 (PSMG1)
Synonyms PAC-1; Chromosome 21 leucine-rich protein; C21-LRP; Down syndrome critical region protein 2
Gene Name PSMG1
Related Disease
Cognitive impairment ( )
Crohn disease ( )
Huntington disease ( )
Rheumatoid arthritis ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Atrial fibrillation ( )
B-cell neoplasm ( )
Benign prostatic hyperplasia ( )
Bipolar disorder ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiac failure ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Congestive heart failure ( )
Glioblastoma multiforme ( )
Glioma ( )
Herpes simplex infection ( )
High blood pressure ( )
Lung cancer ( )
Lung carcinoma ( )
Meningioma ( )
Metabolic disorder ( )
Migraine disorder ( )
Neoplasm ( )
Nervous system inflammation ( )
Neuralgia ( )
Non-small-cell lung cancer ( )
Parkinson disease ( )
Post-traumatic stress disorder ( )
Retinoblastoma ( )
Schizophrenia ( )
Ulcerative colitis ( )
Advanced cancer ( )
Mental disorder ( )
Osteoarthritis ( )
Pancreatic ductal carcinoma ( )
Small lymphocytic lymphoma ( )
Ankylosing spondylitis ( )
Anxiety ( )
Anxiety disorder ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Thyroid gland papillary carcinoma ( )
UniProt ID
PSMG1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF16094
Sequence
MAATFFGEVVKAPCRAGTEDEEEEEEGRRETPEDREVRLQLARKREVRLLRRQTKTSLEV
SLLEKYPCSKFIIAIGNNAVAFLSSFVMNSGVWEEVGCAKLWNEWCRTTDTTHLSSTEAF
CVFYHLKSNPSVFLCQCSCYVAEDQQYQWLEKVFGSCPRKNMQITILTCRHVTDYKTSES
TGSLPSPFLRALKTQNFKDSACCPLLEQPNIVHDLPAAVLSYCQVWKIPAILYLCYTDVM
KLDLITVEAFKPILSTRSLKGLVKNIPQSTEILKKLMTTNEIQSNIYT
Function
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization.
Tissue Specificity In the adult, detected in brain, colon, leukocytes, breast and testis. Widely expressed in the fetus. Also expressed in a variety of proliferating cell lines.

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cognitive impairment DISH2ERD Definitive Biomarker [1]
Crohn disease DIS2C5Q8 Definitive Genetic Variation [2]
Huntington disease DISQPLA4 Definitive Biomarker [1]
Rheumatoid arthritis DISTSB4J Definitive Biomarker [3]
Adenocarcinoma DIS3IHTY Strong Biomarker [4]
Adult glioblastoma DISVP4LU Strong Altered Expression [5]
Atrial fibrillation DIS15W6U Strong Biomarker [6]
B-cell neoplasm DISVY326 Strong Biomarker [7]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [8]
Bipolar disorder DISAM7J2 Strong Biomarker [9]
Brain neoplasm DISY3EKS Strong Altered Expression [10]
Breast cancer DIS7DPX1 Strong Altered Expression [11]
Breast carcinoma DIS2UE88 Strong Altered Expression [11]
Breast neoplasm DISNGJLM Strong Altered Expression [12]
Cardiac failure DISDC067 Strong Biomarker [13]
Colon cancer DISVC52G Strong Biomarker [11]
Colon carcinoma DISJYKUO Strong Biomarker [11]
Colonic neoplasm DISSZ04P Strong Altered Expression [11]
Congestive heart failure DIS32MEA Strong Biomarker [13]
Glioblastoma multiforme DISK8246 Strong Altered Expression [5]
Glioma DIS5RPEH Strong Biomarker [10]
Herpes simplex infection DISL1SAV Strong Biomarker [14]
High blood pressure DISY2OHH Strong Biomarker [15]
Lung cancer DISCM4YA Strong Altered Expression [16]
Lung carcinoma DISTR26C Strong Altered Expression [16]
Meningioma DISPT4TG Strong Biomarker [10]
Metabolic disorder DIS71G5H Strong Biomarker [17]
Migraine disorder DISFCQTG Strong Biomarker [18]
Neoplasm DISZKGEW Strong Genetic Variation [4]
Nervous system inflammation DISB3X5A Strong Biomarker [19]
Neuralgia DISWO58J Strong Biomarker [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [21]
Parkinson disease DISQVHKL Strong Biomarker [22]
Post-traumatic stress disorder DISHL1EY Strong Biomarker [23]
Retinoblastoma DISVPNPB Strong Biomarker [24]
Schizophrenia DISSRV2N Strong Biomarker [25]
Ulcerative colitis DIS8K27O Strong Genetic Variation [26]
Advanced cancer DISAT1Z9 moderate Biomarker [27]
Mental disorder DIS3J5R8 moderate Biomarker [28]
Osteoarthritis DIS05URM moderate Altered Expression [29]
Pancreatic ductal carcinoma DIS26F9Q moderate Biomarker [30]
Small lymphocytic lymphoma DIS30POX moderate Biomarker [31]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [32]
Anxiety DISIJDBA Limited Biomarker [33]
Anxiety disorder DISBI2BT Limited Biomarker [33]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [34]
Prostate cancer DISF190Y Limited Altered Expression [35]
Prostate carcinoma DISMJPLE Limited Altered Expression [35]
Thyroid gland papillary carcinoma DIS48YMM Limited Altered Expression [36]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 Proteasome assembly chaperone 1 (PSMG1). [37]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Proteasome assembly chaperone 1 (PSMG1). [38]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [39]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [40]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [42]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [43]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Proteasome assembly chaperone 1 (PSMG1). [44]
Menadione DMSJDTY Approved Menadione affects the expression of Proteasome assembly chaperone 1 (PSMG1). [44]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [45]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [48]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Proteasome assembly chaperone 1 (PSMG1). [49]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Proteasome assembly chaperone 1 (PSMG1). [50]
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⏷ Show the Full List of 13 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Proteasome assembly chaperone 1 (PSMG1). [46]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Proteasome assembly chaperone 1 (PSMG1). [47]
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References

1 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Enhances Hippocampal Synaptic Plasticity and Improves Memory Performance in Huntington's Disease.Mol Neurobiol. 2018 Nov;55(11):8263-8277. doi: 10.1007/s12035-018-0972-5. Epub 2018 Mar 10.
2 Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis.Inflamm Bowel Dis. 2011 Sep;17(9):1936-42. doi: 10.1002/ibd.21579. Epub 2010 Dec 10.
3 Potential role of platelets for atherosclerotic events in rheumatoid arthritis.FEBS Open Bio. 2018 Nov 6;8(12):1888-1896. doi: 10.1002/2211-5463.12531. eCollection 2018 Dec.
4 PACAP and PAC1 receptor expression in pancreatic ductal carcinoma.Oncol Lett. 2019 Dec;18(6):5725-5730. doi: 10.3892/ol.2019.10971. Epub 2019 Oct 8.
5 Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors. Neurochem Res. 2017 Apr;42(4):943-952. doi: 10.1007/s11064-016-2127-2. Epub 2016 Nov 30.
6 Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study.J Am Heart Assoc. 2018 Nov 20;7(22):e009509. doi: 10.1161/JAHA.118.009509.
7 Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.Oncotarget. 2016 Jan 19;7(3):3461-76. doi: 10.18632/oncotarget.6505.
8 PACAP and type I PACAP receptors in human prostate cancer tissue.Ann N Y Acad Sci. 2006 Jul;1070:440-9. doi: 10.1196/annals.1317.059.
9 Role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin1 systems in schizophrenia and bipolar disorder: novel treatment mechanisms?.Pharmacogenomics. 2009 Dec;10(12):1967-78. doi: 10.2217/pgs.09.147.
10 Immunohistochemical Characterization of Procaspase-3 Overexpression as a Druggable Target With PAC-1, a Procaspase-3 Activator, in Canine and Human Brain Cancers.Front Oncol. 2019 Feb 25;9:96. doi: 10.3389/fonc.2019.00096. eCollection 2019.
11 Differential coupling of the PAC1 SV1 splice variant on human colonic tumors to the activation of intracellular cAMP but not intracellular Ca2+ does not activate tumor proliferation.J Mol Neurosci. 2004;22(1-2):83-92. doi: 10.1385/JMN:22:1-2:83.
12 Pituitary adenylate cyclase-activating peptide/vasoactive intestinal peptide receptors in human normal mammary gland and breast cancer tissue.Gynecol Endocrinol. 2005 Jun;20(6):327-33. doi: 10.1080/09513590500098240.
13 Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the human infant brain and changes in the Sudden Infant Death Syndrome (SIDS).Neurobiol Dis. 2017 Jul;103:70-77. doi: 10.1016/j.nbd.2017.04.002. Epub 2017 Apr 6.
14 A host cell protein binds to a highly conserved sequence element (pac-2) within the cytomegalovirus a sequence.J Virol. 1989 Nov;63(11):4715-28. doi: 10.1128/JVI.63.11.4715-4728.1989.
15 Expression of vasoactive intestinal peptide and related receptors in overcirculation-induced pulmonary hypertension in piglets.Pediatr Res. 2009 Oct;66(4):395-9. doi: 10.1203/PDR.0b013e3181b33804.
16 PACAP-27 tyrosine phosphorylates mitogen activated protein kinase and increases VEGF mRNAs in human lung cancer cells.Regul Pept. 2002 Nov 15;109(1-3):135-40. doi: 10.1016/s0167-0115(02)00196-9.
17 Targeting the PAC1 Receptor for Neurological and Metabolic Disorders.Curr Top Med Chem. 2019;19(16):1399-1417. doi: 10.2174/1568026619666190709092647.
18 Dynamic changes in CGRP, PACAP, and PACAP receptors in the trigeminovascular system of a novel repetitive electrical stimulation rat model: Relevant to migraine.Mol Pain. 2019 Jan-Dec;15:1744806918820452. doi: 10.1177/1744806918820452.
19 PACAP/PAC1 Regulation of Inflammation via Catecholaminergic Neurons in a Model of Multiple Sclerosis.J Mol Neurosci. 2019 Jul;68(3):439-451. doi: 10.1007/s12031-018-1137-8. Epub 2018 Jul 30.
20 Synthesis of a novel and potent small-molecule antagonist of PAC1 receptor for the treatment of neuropathic pain.Eur J Med Chem. 2020 Jan 15;186:111902. doi: 10.1016/j.ejmech.2019.111902. Epub 2019 Nov 19.
21 MiR-34c-3p suppresses the proliferation and invasion of non-small cell lung cancer (NSCLC) by inhibiting PAC1/MAPK pathway.Int J Clin Exp Pathol. 2015 Jun 1;8(6):6312-22. eCollection 2015.
22 New insights about the peculiar role of the 28-38 C-terminal segment and some selected residues in PACAP for signaling and neuroprotection.Biochem Pharmacol. 2018 Aug;154:193-202. doi: 10.1016/j.bcp.2018.04.024. Epub 2018 Apr 25.
23 Neural Mechanism of a Sex-Specific Risk Variant for Posttraumatic Stress Disorder in the Type I Receptor of the Pituitary Adenylate Cyclase Activating Polypeptide.Biol Psychiatry. 2015 Dec 15;78(12):840-7. doi: 10.1016/j.biopsych.2014.12.018. Epub 2015 Jan 9.
24 G-protein-coupled receptor kinase 3- and protein kinase C-mediated desensitization of the PACAP receptor type 1 in human Y-79 retinoblastoma cells.Neuropharmacology. 2001 Mar;40(3):394-407. doi: 10.1016/s0028-3908(00)00167-2.
25 PACAP Protects Adult Neural Stem Cells from the Neurotoxic Effect of Ketamine Associated with Decreased Apoptosis, ER Stress and mTOR Pathway Activation.PLoS One. 2017 Jan 26;12(1):e0170496. doi: 10.1371/journal.pone.0170496. eCollection 2017.
26 Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients.PLoS One. 2011;6(7):e22688. doi: 10.1371/journal.pone.0022688. Epub 2011 Jul 27.
27 Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells.Oncogene. 2020 Jan;39(4):801-813. doi: 10.1038/s41388-019-1010-4. Epub 2019 Sep 25.
28 PACAP and PAC1 receptor in brain development and behavior.Neuropeptides. 2013 Dec;47(6):421-30. doi: 10.1016/j.npep.2013.10.005. Epub 2013 Oct 23.
29 Impaired Proteasomal Function in Human Osteoarthritic Chondrocytes Can Contribute to Decreased Levels of SOX9 and Aggrecan.Arthritis Rheumatol. 2018 Jul;70(7):1030-1041. doi: 10.1002/art.40456. Epub 2018 May 27.
30 Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2'-deoxyzebularine.J Med Chem. 2008 Dec 11;51(23):7593-601. doi: 10.1021/jm8005965.
31 Expression of executioner procaspases and their activation by a procaspase-activating compound in chronic lymphocytic leukemia cells.Blood. 2015 Feb 12;125(7):1126-36. doi: 10.1182/blood-2014-01-546796. Epub 2014 Dec 23.
32 Association of variants in 21q22 with ankylosing spondylitis in the Chinese Guangxi Zhuang population.Rheumatol Int. 2014 Sep;34(9):1251-5. doi: 10.1007/s00296-014-2973-7. Epub 2014 Mar 19.
33 Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder.Psychiatry Res. 2013 Dec 30;210(3):1299-300. doi: 10.1016/j.psychres.2013.07.038. Epub 2013 Aug 22.
34 Targeting executioner procaspase-3 with the procaspase-activating compound B-PAC-1 induces apoptosis in multiple myeloma cells.Exp Hematol. 2015 Nov;43(11):951-962.e3. doi: 10.1016/j.exphem.2015.07.005. Epub 2015 Aug 6.
35 PAC1-R null isoform expression in human prostate cancer tissue.Prostate. 2006 Apr 1;66(5):514-21. doi: 10.1002/pros.20356.
36 Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.J Mol Neurosci. 2016 Oct;60(2):171-8. doi: 10.1007/s12031-016-0823-7. Epub 2016 Aug 26.
37 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
38 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
39 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
40 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
41 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
42 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
43 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
44 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
45 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
46 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
47 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
48 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
49 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
50 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.