Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKSACR4)

DOT Name B-cell receptor-associated protein 31 (BCAP31)
Synonyms BCR-associated protein 31; Bap31; 6C6-AG tumor-associated antigen; Protein CDM; p28
Gene Name BCAP31
Related Disease
B-cell neoplasm ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome ( )
Adrenoleukodystrophy ( )
Adult T-cell leukemia/lymphoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Autoimmune disease ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of esophagus ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cystic fibrosis ( )
Depression ( )
Dystonia ( )
Encephalitis ( )
Familial dilated cardiomyopathy ( )
Fatty liver disease ( )
Gastric cancer ( )
Glioma ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Intellectual disability ( )
Limb-girdle muscular dystrophy ( )
Multiple sclerosis ( )
Myocardial infarction ( )
Myopathy ( )
Myopia ( )
Neoplasm ( )
Obesity ( )
Psoriasis ( )
Schizophrenia ( )
Stomach cancer ( )
Triple negative breast cancer ( )
Zellweger spectrum disorders ( )
Influenza ( )
Melanoma ( )
Movement disorder ( )
Cardiomyopathy ( )
Cholestasis ( )
Colorectal carcinoma ( )
Nervous system inflammation ( )
Sensorineural hearing loss disorder ( )
UniProt ID
BAP31_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4JZL; 4JZP
Pfam ID
PF05529 ; PF18035
Sequence
MSLQWTAVATFLYAEVFVVLLLCIPFISPKRWQKIFKSRLVELLVSYGNTFFVVLIVILV
LLVIDAVREIRKYDDVTEKVNLQNNPGAMEHFHMKLFRAQRNLYIAGFSLLLSFLLRRLV
TLISQQATLLASNEAFKKQAESASEAAKKYMEENDQLKKGAAVDGGKLDVGNAEVKLEEE
NRSLKADLQKLKDELASTKQKLEKAENQVLAMRKQSEGLTKEYDRLLEEHAKLQAAVDGP
MDKKEE
Function
Functions as a chaperone protein. Is one of the most abundant endoplasmic reticulum (ER) proteins. Plays a role in the export of secreted proteins in the ER, the recognition of abnormally folded protein and their targeting to the ER associated-degradation (ERAD). Also serves as a cargo receptor for the export of transmembrane proteins. Plays a role in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by stimulating the translocation of NDUFS4 and NDUFB11 from the cytosol to the mitochondria via interaction with TOMM40. In response to ER stress, delocalizes from the ER-mitochondria contact sites and binds BCL2. May be involved in CASP8-mediated apoptosis.
Tissue Specificity Ubiquitous. Highly expressed in neurons and discrete endocrine cells.
KEGG Pathway
Protein processing in endoplasmic reticulum (hsa04141 )
Human papillomavirus infection (hsa05165 )
Reactome Pathway
Apoptotic execution phase (R-HSA-75153 )
RHOA GTPase cycle (R-HSA-8980692 )
Antigen Presentation (R-HSA-983170 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell neoplasm DISVY326 Definitive Altered Expression [1]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Definitive Biomarker [2]
Liver cancer DISDE4BI Definitive Biomarker [2]
Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome DISL0P18 Definitive X-linked [3]
Adrenoleukodystrophy DISTUD1F Strong Biomarker [4]
Adult T-cell leukemia/lymphoma DIS882XU Strong Altered Expression [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Alzheimer disease DISF8S70 Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
Brain neoplasm DISY3EKS Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Carcinoma of esophagus DISS6G4D Strong Biomarker [11]
Cervical cancer DISFSHPF Strong Biomarker [6]
Cervical carcinoma DIST4S00 Strong Biomarker [6]
Cystic fibrosis DIS2OK1Q Strong Genetic Variation [12]
Depression DIS3XJ69 Strong Genetic Variation [13]
Dystonia DISJLFGW Strong Genetic Variation [4]
Encephalitis DISLD1RL Strong Biomarker [14]
Familial dilated cardiomyopathy DISBHDU9 Strong Biomarker [15]
Fatty liver disease DIS485QZ Strong Biomarker [16]
Gastric cancer DISXGOUK Strong Biomarker [17]
Glioma DIS5RPEH Strong Biomarker [9]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [18]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [19]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [20]
High blood pressure DISY2OHH Strong Genetic Variation [13]
Intellectual disability DISMBNXP Strong Genetic Variation [12]
Limb-girdle muscular dystrophy DISI9Y1Z Strong Genetic Variation [15]
Multiple sclerosis DISB2WZI Strong Biomarker [8]
Myocardial infarction DIS655KI Strong Altered Expression [21]
Myopathy DISOWG27 Strong Biomarker [15]
Myopia DISK5S60 Strong Biomarker [22]
Neoplasm DISZKGEW Strong Biomarker [23]
Obesity DIS47Y1K Strong Biomarker [16]
Psoriasis DIS59VMN Strong Altered Expression [24]
Schizophrenia DISSRV2N Strong Genetic Variation [25]
Stomach cancer DISKIJSX Strong Biomarker [17]
Triple negative breast cancer DISAMG6N Strong Biomarker [26]
Zellweger spectrum disorders DISW52CE Strong Biomarker [27]
Influenza DIS3PNU3 moderate Altered Expression [28]
Melanoma DIS1RRCY moderate Biomarker [29]
Movement disorder DISOJJ2D moderate Biomarker [30]
Cardiomyopathy DISUPZRG Limited Biomarker [31]
Cholestasis DISDJJWE Limited Biomarker [4]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [23]
Nervous system inflammation DISB3X5A Limited Altered Expression [32]
Sensorineural hearing loss disorder DISJV45Z Limited Genetic Variation [30]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Etoposide DMNH3PG Approved B-cell receptor-associated protein 31 (BCAP31) increases the Cell death ADR of Etoposide. [46]
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2 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 B-cell receptor-associated protein 31 (BCAP31). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of B-cell receptor-associated protein 31 (BCAP31). [43]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of B-cell receptor-associated protein 31 (BCAP31). [34]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of B-cell receptor-associated protein 31 (BCAP31). [35]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of B-cell receptor-associated protein 31 (BCAP31). [36]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of B-cell receptor-associated protein 31 (BCAP31). [37]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of B-cell receptor-associated protein 31 (BCAP31). [38]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of B-cell receptor-associated protein 31 (BCAP31). [39]
Aminoglutethimide DMWFHMZ Approved Aminoglutethimide decreases the expression of B-cell receptor-associated protein 31 (BCAP31). [40]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of B-cell receptor-associated protein 31 (BCAP31). [41]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of B-cell receptor-associated protein 31 (BCAP31). [42]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of B-cell receptor-associated protein 31 (BCAP31). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of B-cell receptor-associated protein 31 (BCAP31). [45]
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⏷ Show the Full List of 11 Drug(s)

References

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4 Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1.Clin Genet. 2015 Feb;87(2):141-7. doi: 10.1111/cge.12355. Epub 2014 Mar 6.
5 Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo.Retrovirology. 2008 May 12;5:38. doi: 10.1186/1742-4690-5-38.
6 Inhibition of BAP31 expression inhibits cervical cancer progression by suppressing metastasis and inducing intrinsic and extrinsic apoptosis.Biochem Biophys Res Commun. 2019 Jan 8;508(2):499-506. doi: 10.1016/j.bbrc.2018.11.017. Epub 2018 Nov 30.
7 BAP31 deficiency contributes to the formation of amyloid- plaques in Alzheimer's disease by reducing the stability of RTN3.FASEB J. 2019 Apr;33(4):4936-4946. doi: 10.1096/fj.201801702R. Epub 2018 Dec 31.
8 Interleukin-27 Gene Therapy Prevents the Development of Autoimmune Encephalomyelitis but Fails to Attenuate Established Inflammation due to the Expansion of CD11b(+)Gr-1(+) Myeloid Cells.Front Immunol. 2018 Apr 24;9:873. doi: 10.3389/fimmu.2018.00873. eCollection 2018.
9 Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies.Int Microbiol. 2019 Dec;22(4):437-449. doi: 10.1007/s10123-019-00070-8. Epub 2019 Mar 20.
10 Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy.Theranostics. 2018 Feb 7;8(6):1558-1574. doi: 10.7150/thno.22989. eCollection 2018.
11 Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer.Cancer Biol Ther. 2010 Jan;9(2):88-95. doi: 10.4161/cbt.9.2.10283. Epub 2010 Jan 9.
12 B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2.Cell Physiol Biochem. 2018;51(4):1799-1814. doi: 10.1159/000495682. Epub 2018 Nov 30.
13 Analysis of treatment pathways for three chronic diseases using OMOP CDM.J Med Syst. 2018 Nov 13;42(12):260. doi: 10.1007/s10916-018-1076-5.
14 Dysregulation of sonic hedgehog pathway and pericytes in the brain after lentiviral infection.J Neuroinflammation. 2019 Apr 13;16(1):86. doi: 10.1186/s12974-019-1463-y.
15 Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23.Am J Hum Genet. 1997 Oct;61(4):909-17. doi: 10.1086/514896.
16 Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice.J Lipid Res. 2018 Jan;59(1):35-47. doi: 10.1194/jlr.M077016. Epub 2017 Nov 7.
17 A BAP31 intrabody induces gastric cancer cell death by inhibiting p27(kip1) proteasome degradation.Int J Cancer. 2019 Apr 15;144(8):2051-2062. doi: 10.1002/ijc.31930. Epub 2019 Jan 17.
18 Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma.Science. 1985 Jan 25;227(4685):429-33. doi: 10.1126/science.2981434.
19 Interleukin 27 polymorphisms in HCV RNA positive patients: is there an impact on response to interferon therapy?.BMC Infect Dis. 2014;14 Suppl 5(Suppl 5):S5. doi: 10.1186/1471-2334-14-S5-S5. Epub 2014 Sep 5.
20 Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism.Mol Biosyst. 2016 Apr 26;12(5):1496-506. doi: 10.1039/c5mb00827a.
21 Profiling analysis of long non-coding RNAs in early postnatal mouse hearts.Sci Rep. 2017 Mar 7;7:43485. doi: 10.1038/srep43485.
22 Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4362-70. doi: 10.1167/iovs.09-3998. Epub 2010 May 19.
23 MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer.Cell Death Dis. 2019 Feb 15;10(3):152. doi: 10.1038/s41419-019-1403-x.
24 BCAP 31 expression and promoter demethylation in psoriasis.Asian Pac J Allergy Immunol. 2017 Jun;35(2):86-90. doi: 10.12932/AP0818.
25 Early Development of Parvalbumin-, Somatostatin-, and Cholecystokinin-Expressing Neurons in Rat Brain following Prenatal Immune Activation and Maternal Iron Deficiency.Dev Neurosci. 2016;38(5):342-353. doi: 10.1159/000454677. Epub 2017 Feb 18.
26 BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation.Theranostics. 2019 Aug 21;9(22):6468-6484. doi: 10.7150/thno.35383. eCollection 2019.
27 Contiguous ABCD1 DXS1357E deletion syndrome: report of an autopsy case.Neuropathology. 2013 Jun;33(3):292-8. doi: 10.1111/j.1440-1789.2012.01348.x. Epub 2012 Sep 21.
28 Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity.Front Microbiol. 2019 Mar 6;10:432. doi: 10.3389/fmicb.2019.00432. eCollection 2019.
29 BAP31, a promising target for the immunotherapy of malignant melanomas.J Exp Clin Cancer Res. 2015 Apr 18;34(1):36. doi: 10.1186/s13046-015-0153-6.
30 BCAP31-associated encephalopathy and complex movement disorder mimicking mitochondrial encephalopathy.Am J Med Genet A. 2017 Jun;173(6):1640-1643. doi: 10.1002/ajmg.a.38127. Epub 2017 Mar 23.
31 Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: A new mechanism involving BAP31 upregulation and MAPK-ERK pathway.J Cell Physiol. 2020 Mar;235(3):2847-2856. doi: 10.1002/jcp.29190. Epub 2019 Sep 18.
32 IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells.J Immunol. 2009 May 1;182(9):5748-56. doi: 10.4049/jimmunol.0801162.
33 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.
34 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.
35 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
36 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
37 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.
38 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
39 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
40 Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
41 Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
42 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
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45 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
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