Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT071TET)

DOT Name Marginal zone B- and B1-cell-specific protein (MZB1)
Synonyms Mesenteric estrogen-dependent adipose 7; MEDA-7; Plasma cell-induced resident endoplasmic reticulum protein; Plasma cell-induced resident ER protein; pERp1; Proapoptotic caspase adapter protein
Gene Name MZB1
Related Disease
OPTN-related open angle glaucoma ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Anxiety disorder ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease ( )
B-cell lymphoma ( )
Benign prostatic hyperplasia ( )
Bronchopulmonary dysplasia ( )
Depression ( )
Follicular lymphoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Kaposi sarcoma ( )
Kidney failure ( )
Knee osteoarthritis ( )
Lung cancer ( )
Lung carcinoma ( )
Matthew-Wood syndrome ( )
Mental disorder ( )
Migraine disorder ( )
Multiple sclerosis ( )
Neoplasm ( )
Nephrotic syndrome ( )
Nervous system inflammation ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Obesity ( )
Parkinson disease ( )
Pheochromocytoma ( )
Post-traumatic stress disorder ( )
Prostate cancer ( )
Prostate carcinoma ( )
Retinoblastoma ( )
Small lymphocytic lymphoma ( )
Small-cell lung cancer ( )
Stomach cancer ( )
Systemic lupus erythematosus ( )
Neuralgia ( )
Type-1/2 diabetes ( )
Gastric neoplasm ( )
Anxiety ( )
Plasma cell myeloma ( )
Stroke ( )
Thyroid gland papillary carcinoma ( )
UniProt ID
MZB1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
7AAH
Pfam ID
PF11938
Sequence
MRLSLPLLLLLLGAWAIPGGLGDRAPLTATAPQLDDEEMYSAHMPAHLRCDACRAVAYQM
WQNLAKAETKLHTSNSGGRRELSELVYTDVLDRSCSRNWQDYGVREVDQVKRLTGPGLSE
GPEPSISVMVTGGPWPTRLSRTCLHYLGEFGEDQIYEAHQQGRGALEALLCGGPQGACSE
KVSATREEL
Function
Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion. May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of oxidoreductase activity. Isoform 2 may be involved in regulation of apoptosis. Helps to diversify peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation; Acts as a hormone-regulated adipokine/pro-inflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the onset of insulin resistance.
Tissue Specificity
Widely expressed with highest levels in adult brain, small intestine and lymphoid tissues such as thymus and spleen. Expression is frequently lower in intestinal-type gastric cancer. In obese patients, more abundant in omental than in subcutaneous fat.

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
OPTN-related open angle glaucoma DISDR98A Definitive Altered Expression [1]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [2]
Adult glioblastoma DISVP4LU Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Altered Expression [5]
Anxiety disorder DISBI2BT Strong Biomarker [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
B-cell lymphoma DISIH1YQ Strong Altered Expression [2]
Benign prostatic hyperplasia DISI3CW2 Strong Altered Expression [9]
Bronchopulmonary dysplasia DISO0BY5 Strong Genetic Variation [10]
Depression DIS3XJ69 Strong Biomarker [11]
Follicular lymphoma DISVEUR6 Strong Altered Expression [2]
Gastric cancer DISXGOUK Strong Altered Expression [12]
Glioblastoma multiforme DISK8246 Strong Altered Expression [3]
Hepatocellular carcinoma DIS0J828 Strong Posttranslational Modification [13]
Kaposi sarcoma DISC1H1Z Strong Biomarker [4]
Kidney failure DISOVQ9P Strong Biomarker [14]
Knee osteoarthritis DISLSNBJ Strong Biomarker [15]
Lung cancer DISCM4YA Strong Biomarker [16]
Lung carcinoma DISTR26C Strong Biomarker [16]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [17]
Mental disorder DIS3J5R8 Strong Biomarker [18]
Migraine disorder DISFCQTG Strong Biomarker [19]
Multiple sclerosis DISB2WZI Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Nephrotic syndrome DISSPSC2 Strong Biomarker [22]
Nervous system inflammation DISB3X5A Strong Biomarker [20]
Neuroblastoma DISVZBI4 Strong Biomarker [23]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [24]
Obesity DIS47Y1K Strong Biomarker [25]
Parkinson disease DISQVHKL Strong Altered Expression [26]
Pheochromocytoma DIS56IFV Strong Altered Expression [27]
Post-traumatic stress disorder DISHL1EY Strong Biomarker [28]
Prostate cancer DISF190Y Strong Altered Expression [9]
Prostate carcinoma DISMJPLE Strong Altered Expression [9]
Retinoblastoma DISVPNPB Strong Biomarker [29]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [2]
Small-cell lung cancer DISK3LZD Strong Altered Expression [30]
Stomach cancer DISKIJSX Strong Altered Expression [12]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [31]
Neuralgia DISWO58J moderate Altered Expression [32]
Type-1/2 diabetes DISIUHAP moderate Genetic Variation [33]
Gastric neoplasm DISOKN4Y Disputed Altered Expression [34]
Anxiety DISIJDBA Limited Biomarker [6]
Plasma cell myeloma DIS0DFZ0 Limited Altered Expression [2]
Stroke DISX6UHX Limited Genetic Variation [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
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Marginal zone B- and B1-cell-specific protein (MZB1). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Marginal zone B- and B1-cell-specific protein (MZB1). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Marginal zone B- and B1-cell-specific protein (MZB1). [43]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Marginal zone B- and B1-cell-specific protein (MZB1). [38]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Marginal zone B- and B1-cell-specific protein (MZB1). [39]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Marginal zone B- and B1-cell-specific protein (MZB1). [40]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Marginal zone B- and B1-cell-specific protein (MZB1). [42]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Marginal zone B- and B1-cell-specific protein (MZB1). [40]
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References

1 Transcriptomic and proteomic analysis of iris tissue and aqueous humor in juvenile idiopathic arthritis-associated uveitis.J Autoimmun. 2019 Jun;100:75-83. doi: 10.1016/j.jaut.2019.03.004. Epub 2019 Mar 15.
2 High expression of MZB1 predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature.Leuk Lymphoma. 2013 Aug;54(8):1652-7. doi: 10.3109/10428194.2012.753445. Epub 2012 Dec 27.
3 The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line. Acta Neurobiol Exp (Wars). 2017;77(3):205-213.
4 The product of Kaposi's sarcoma-associated herpesvirus immediate early gene K4.2 regulates immunoglobulin secretion and calcium homeostasis by interacting with and inhibiting pERP1.J Virol. 2013 Nov;87(22):12069-79. doi: 10.1128/JVI.01900-13. Epub 2013 Aug 28.
5 Pituitary adenylate cyclase-activating polypeptide protects against -amyloid toxicity.Neurobiol Aging. 2014 Sep;35(9):2064-71. doi: 10.1016/j.neurobiolaging.2014.03.022. Epub 2014 Mar 22.
6 PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse.Elife. 2018 Jun 15;7:e35960. doi: 10.7554/eLife.35960.
7 PACAP deficiency aggravates atherosclerosis in ApoE deficient mice.Immunobiology. 2019 Jan;224(1):124-132. doi: 10.1016/j.imbio.2018.09.008. Epub 2018 Oct 26.
8 Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis.Am J Respir Crit Care Med. 2017 Nov 15;196(10):1298-1310. doi: 10.1164/rccm.201611-2263OC.
9 PAC1-R null isoform expression in human prostate cancer tissue.Prostate. 2006 Apr 1;66(5):514-21. doi: 10.1002/pros.20356.
10 Association analysis of the pituitary adenylate cyclase-activating polypeptide (PACAP/ADCYAP1) gene in bipolar disorder.Psychiatr Genet. 2008 Apr;18(2):53-8. doi: 10.1097/YPG.0b013e3282f60320.
11 Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background.Neuroscience. 2017 Jun 23;354:11-29. doi: 10.1016/j.neuroscience.2017.04.019. Epub 2017 Apr 25.
12 Epigenetic suppression of the immunoregulator MZB1 is associated with the malignant phenotype of gastric cancer.Int J Cancer. 2016 Nov 15;139(10):2290-8. doi: 10.1002/ijc.30286. Epub 2016 Aug 6.
13 Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor suppressor in hepatocellular carcinoma.Clin Cancer Res. 2012 Jul 1;18(13):3541-51. doi: 10.1158/1078-0432.CCR-11-1007. Epub 2012 May 9.
14 Treatment of renal failure associated with multiple myeloma and other diseases by PACAP-38.Ann N Y Acad Sci. 2006 Jul;1070:1-4. doi: 10.1196/annals.1317.093.
15 The synovial fluid neuropeptide PACAP may act as a protective factor during disease progression of primary knee osteoarthritis and is increased following hyaluronic acid injection.Innate Immun. 2019 May;25(4):255-264. doi: 10.1177/1753425919839125. Epub 2019 Apr 1.
16 VIP and PACAP receptors coupled to adenylyl cyclase in human lung cancer: a study in biopsy specimens.Peptides. 2003 Mar;24(3):429-36. doi: 10.1016/s0196-9781(03)00058-5.
17 MZB1 in borderline resectable pancreatic cancer resected after neoadjuvant chemoradiotherapy.J Surg Res. 2017 Dec;220:391-401. doi: 10.1016/j.jss.2017.07.003. Epub 2017 Sep 3.
18 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.
19 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.
20 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.
21 Signaling pathways activated by PACAP in MCF-7 breast cancer cells.Cell Signal. 2018 Oct;50:37-47. doi: 10.1016/j.cellsig.2018.06.009. Epub 2018 Jun 20.
22 Pituitary adenylate cyclase-activating polypeptide (PACAP) in zebrafish models of nephrotic syndrome.PLoS One. 2017 Jul 31;12(7):e0182100. doi: 10.1371/journal.pone.0182100. eCollection 2017.
23 PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia.Neuropeptides. 2018 Jun;69:84-91. doi: 10.1016/j.npep.2018.04.009. Epub 2018 Apr 17.
24 PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner.Peptides. 2019 Oct;120:170017. doi: 10.1016/j.peptides.2018.09.005. Epub 2018 Sep 28.
25 Novel hormone-regulated genes in visceral adipose tissue: cloning and identification of proinflammatory cytokine-like mouse and human MEDA-7: implications for obesity, insulin resistance and the metabolic syndrome.Diabetologia. 2011 Sep;54(9):2368-80. doi: 10.1007/s00125-011-2212-7. Epub 2011 Jun 19.
26 Alteration of the PAC1 Receptor Expression in the Basal Ganglia of MPTP-Induced Parkinsonian Macaque Monkeys.Neurotox Res. 2018 May;33(4):702-715. doi: 10.1007/s12640-017-9841-7. Epub 2017 Dec 11.
27 Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis.Regul Pept. 2003 Feb 28;110(3):213-7. doi: 10.1016/s0167-0115(02)00209-4.
28 Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling in the prefrontal cortex modulates cued fear learning, but not spatial working memory, in female rats.Neuropharmacology. 2018 May 1;133:145-154. doi: 10.1016/j.neuropharm.2018.01.010. Epub 2018 Jan 17.
29 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.
30 PACAP stimulates c-fos mRNAs in small cell lung cancer cells.Life Sci. 1996;59(4):307-13. doi: 10.1016/0024-3205(96)00299-8.
31 Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes.Arthritis Res Ther. 2018 Jan 30;20(1):13. doi: 10.1186/s13075-018-1511-5.
32 Parabrachial Pituitary Adenylate Cyclase-Activating Polypeptide Activation of Amygdala Endosomal Extracellular Signal-Regulated Kinase Signaling Regulates the Emotional Component of Pain.Biol Psychiatry. 2017 Apr 15;81(8):671-682. doi: 10.1016/j.biopsych.2016.08.025. Epub 2016 Aug 29.
33 Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: potential role of C-peptide.Diabetes Res Clin Pract. 2007 Dec;78(3):e1-6. doi: 10.1016/j.diabres.2007.04.010. Epub 2007 Jun 4.
34 MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, encodes secreted-type protein with conserved cysteine residues.Int J Oncol. 2003 Jul;23(1):235-41.
35 Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors.Cell Physiol Biochem. 2018;51(4):1982-1995. doi: 10.1159/000495722. Epub 2018 Dec 4.
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 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
38 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
39 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
40 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
41 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
42 BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
43 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.