Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCAX3AW)

DOT Name Prohibitin-2 (PHB2)
Synonyms B-cell receptor-associated protein BAP37; D-prohibitin; Repressor of estrogen receptor activity
Gene Name PHB2
Related Disease
B-cell neoplasm ( )
Bacteremia ( )
Adult lymphoma ( )
Alzheimer disease ( )
Arthritis ( )
Atrial fibrillation ( )
B-cell lymphoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Choriocarcinoma ( )
Colorectal carcinoma ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Estrogen-receptor positive breast cancer ( )
Head-neck squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Inflammation ( )
leukaemia ( )
Leukemia ( )
Lymphoma ( )
Medullary thyroid gland carcinoma ( )
Neoplasm ( )
Nephropathy ( )
Nephrotic syndrome ( )
Obstructive sleep apnea ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pediatric lymphoma ( )
Polycystic kidney disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rhabdomyosarcoma ( )
Severe combined immunodeficiency ( )
Skin disease ( )
Squamous cell carcinoma ( )
Subarachnoid hemorrhage ( )
Tuberculosis ( )
Uveal Melanoma ( )
Pancreatic cancer ( )
Type-1/2 diabetes ( )
Anxiety ( )
Anxiety disorder ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Small lymphocytic lymphoma ( )
UniProt ID
PHB2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6IQE
Pfam ID
PF01145
Sequence
MAQNLKDLAGRLPAGPRGMGTALKLLLGAGAVAYGVRESVFTVEGGHRAIFFNRIGGVQQ
DTILAEGLHFRIPWFQYPIIYDIRARPRKISSPTGSKDLQMVNISLRVLSRPNAQELPSM
YQRLGLDYEERVLPSIVNEVLKSVVAKFNASQLITQRAQVSLLIRRELTERAKDFSLILD
DVAITELSFSREYTAAVEAKQVAQQEAQRAQFLVEKAKQEQRQKIVQAEGEAEAAKMLGE
ALSKNPGYIKLRKIRAAQNISKTIATSQNRIYLTADNLVLNLQDESFTRGSDSLIKGKK
Function
Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus; In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity. Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 ; In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity; In the plasma membrane, is involved in IGFBP6-induced cell migration. Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation; (Microbial infection) Involved in human enterovirus 71/EV-71 infection by enhancing the autophagy mechanism during the infection.
KEGG Pathway
Mitophagy - animal (hsa04137 )
Reactome Pathway
Processing of SMDT1 (R-HSA-8949664 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell neoplasm DISVY326 Definitive Biomarker [1]
Bacteremia DIS6N9RZ Definitive Genetic Variation [2]
Adult lymphoma DISK8IZR Strong Altered Expression [3]
Alzheimer disease DISF8S70 Strong Altered Expression [4]
Arthritis DIST1YEL Strong Biomarker [5]
Atrial fibrillation DIS15W6U Strong Biomarker [6]
B-cell lymphoma DISIH1YQ Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Altered Expression [9]
Choriocarcinoma DISDBVNL Strong Altered Expression [10]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [11]
Endometriosis DISX1AG8 Strong Biomarker [12]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [13]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [14]
Estrogen-receptor positive breast cancer DIS1H502 Strong Biomarker [15]
Head-neck squamous cell carcinoma DISF7P24 Strong Genetic Variation [16]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [17]
Inflammation DISJUQ5T Strong Biomarker [18]
leukaemia DISS7D1V Strong Altered Expression [3]
Leukemia DISNAKFL Strong Altered Expression [3]
Lymphoma DISN6V4S Strong Altered Expression [3]
Medullary thyroid gland carcinoma DISHBL3K Strong Biomarker [19]
Neoplasm DISZKGEW Strong Biomarker [20]
Nephropathy DISXWP4P Strong Biomarker [21]
Nephrotic syndrome DISSPSC2 Strong Biomarker [22]
Obstructive sleep apnea DIS0SVD1 Strong Genetic Variation [23]
Ovarian cancer DISZJHAP Strong Altered Expression [13]
Ovarian neoplasm DISEAFTY Strong Altered Expression [13]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [3]
Polycystic kidney disease DISWS3UY Strong Genetic Variation [24]
Prostate cancer DISF190Y Strong Altered Expression [25]
Prostate carcinoma DISMJPLE Strong Altered Expression [25]
Rhabdomyosarcoma DISNR7MS Strong Biomarker [26]
Severe combined immunodeficiency DIS6MF4Q Strong Biomarker [27]
Skin disease DISDW8R6 Strong Genetic Variation [22]
Squamous cell carcinoma DISQVIFL Strong Biomarker [28]
Subarachnoid hemorrhage DISI7I8Y Strong Biomarker [29]
Tuberculosis DIS2YIMD Strong Biomarker [30]
Uveal Melanoma DISA7ZGL Strong Biomarker [31]
Pancreatic cancer DISJC981 moderate Biomarker [32]
Type-1/2 diabetes DISIUHAP moderate Biomarker [33]
Anxiety DISIJDBA Limited Biomarker [34]
Anxiety disorder DISBI2BT Limited Biomarker [34]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [35]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [17]
Lung cancer DISCM4YA Limited Altered Expression [36]
Lung carcinoma DISTR26C Limited Altered Expression [36]
Small lymphocytic lymphoma DIS30POX Limited Genetic Variation [37]
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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
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Prohibitin-2 (PHB2). [38]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Prohibitin-2 (PHB2). [39]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Prohibitin-2 (PHB2). [40]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Prohibitin-2 (PHB2). [39]
Aspirin DM672AH Approved Aspirin decreases the expression of Prohibitin-2 (PHB2). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Prohibitin-2 (PHB2). [42]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Prohibitin-2 (PHB2). [43]
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⏷ Show the Full List of 7 Drug(s)

References

1 Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats.Stroke. 2019 Apr;50(4):978-988. doi: 10.1161/STROKEAHA.118.021590.
2 Number of positive blood cultures, biofilm formation, and adhesin genes in differentiating true coagulase-negative staphylococci bacteremia from contamination.Eur J Clin Microbiol Infect Dis. 2016 Jan;35(1):57-66. doi: 10.1007/s10096-015-2506-7.
3 The prohibitin protein complex promotes mitochondrial stabilization and cell survival in hematologic malignancies.Oncotarget. 2017 Jul 1;8(39):65445-65456. doi: 10.18632/oncotarget.18920. eCollection 2017 Sep 12.
4 Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer's disease progression.Sci Rep. 2017 Aug 22;7(1):9115. doi: 10.1038/s41598-017-09481-x.
5 A chromosomal Borrelia burgdorferi gene encodes a 22-kilodalton lipoprotein, P22, that is serologically recognized in Lyme disease.J Clin Microbiol. 1994 Apr;32(4):876-83. doi: 10.1128/jcm.32.4.876-883.1994.
6 Comparing severity scores in exacerbations of chronic obstructive pulmonary disease.Clin Respir J. 2018 Dec;12(12):2668-2675. doi: 10.1111/crj.12973.
7 Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects.J Exp Clin Cancer Res. 2019 Nov 4;38(1):450. doi: 10.1186/s13046-019-1440-4.
8 Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway.J Cell Physiol. 2019 Feb;234(2):1904-1912. doi: 10.1002/jcp.27066. Epub 2018 Aug 26.
9 Expression of a repressor of estrogen receptor activity in human breast tumors: relationship to some known prognostic markers.Cancer Res. 2000 Jun 1;60(11):2796-9.
10 Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors.Cancer Res. 2006 Jan 15;66(2):820-7. doi: 10.1158/0008-5472.CAN-05-2445.
11 Low expression of B-Cell-Associated protein 31 is associated with unfavorable prognosis in human colorectal cancer.Pathol Res Pract. 2018 May;214(5):661-666. doi: 10.1016/j.prp.2018.03.023. Epub 2018 Mar 31.
12 Multiple Beneficial Roles of Repressor of Estrogen Receptor Activity (REA) in Suppressing the Progression of Endometriosis.Endocrinology. 2016 Feb;157(2):900-12. doi: 10.1210/en.2015-1324. Epub 2015 Dec 14.
13 Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling.Cancers (Basel). 2019 Sep 12;11(9):1350. doi: 10.3390/cancers11091350.
14 Tissue-based quantitative proteomics to screen and identify the potential biomarkers for early recurrence/metastasis of esophageal squamous cell carcinoma.Cancer Med. 2018 Jun;7(6):2504-2517. doi: 10.1002/cam4.1463. Epub 2018 Apr 23.
15 Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer.J Nanobiotechnology. 2018 Feb 20;16(1):17. doi: 10.1186/s12951-018-0345-2.
16 Genomic assessments of the frequent loss of heterozygosity region on 8p21.3-p22 in head and neck squamous cell carcinoma.Cancer Genet Cytogenet. 2007 Jul 15;176(2):100-6. doi: 10.1016/j.cancergencyto.2007.04.003.
17 Hepatitis B Virus Precore Protein p22 Inhibits Alpha Interferon Signaling by Blocking STAT Nuclear Translocation.J Virol. 2019 Jun 14;93(13):e00196-19. doi: 10.1128/JVI.00196-19. Print 2019 Jul 1.
18 Dynamic Contrast-Enhanced MR with Quantitative Perfusion Analysis of Small Bowel in Vascular Assessment between Inflammatory and Fibrotic Lesions in Crohn's Disease: A Feasibility Study.Contrast Media Mol Imaging. 2019 Feb 4;2019:1767620. doi: 10.1155/2019/1767620. eCollection 2019.
19 Site-directed chromosome rearrangements in skin fibroblasts from persons carrying genes for hereditary neoplasms.Cancer Res. 1980 Dec;40(12):4796-803.
20 Targeted OMA1 therapies for cancer.Int J Cancer. 2019 Nov 1;145(9):2330-2341. doi: 10.1002/ijc.32177. Epub 2019 Feb 21.
21 Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation.Am J Physiol Renal Physiol. 2019 Feb 1;316(2):F396-F407. doi: 10.1152/ajprenal.00420.2018. Epub 2018 Dec 12.
22 Minimal change nephrotic syndrome and prohibitin-2 gene polymorphism.Clin Exp Nephrol. 2017 Aug;21(4):665-670. doi: 10.1007/s10157-016-1325-1. Epub 2016 Nov 4.
23 Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?.Antioxid Redox Signal. 2012 Jan 15;16(2):171-7. doi: 10.1089/ars.2011.4189. Epub 2011 Oct 12.
24 Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient Mice.J Am Soc Nephrol. 2018 Sep;29(9):2310-2325. doi: 10.1681/ASN.2018010074. Epub 2018 Jul 24.
25 Prohibitin-2 negatively regulates AKT2 expression to promote prostate cancer cell migration.Int J Mol Med. 2018 Feb;41(2):1147-1155. doi: 10.3892/ijmm.2017.3307. Epub 2017 Dec 4.
26 Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA transcription and facilitate cell proliferation in RD cells.Sci Rep. 2018 Jan 24;8(1):1479. doi: 10.1038/s41598-018-19917-7.
27 Evaluation of the relationship between [18F]FDG and P-glycoprotein expression: an experimental study.Nucl Med Biol. 2012 Jul;39(5):671-8. doi: 10.1016/j.nucmedbio.2011.12.007. Epub 2012 Jan 20.
28 Apoptotic cell death induced by baccatin III, a precursor of paclitaxel, may occur without G(2)/M arrest.Cancer Chemother Pharmacol. 1999;44(6):444-52. doi: 10.1007/s002800051117.
29 Mitoquinone attenuates blood-brain barrier disruption through Nrf2/PHB2/OPA1 pathway after subarachnoid hemorrhage in rats.Exp Neurol. 2019 Jul;317:1-9. doi: 10.1016/j.expneurol.2019.02.009. Epub 2019 Feb 16.
30 Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis.Clin Proteomics. 2017 Nov 2;14:36. doi: 10.1186/s12014-017-9171-z. eCollection 2017.
31 PARP Inhibition Increases the Response to Chemotherapy in Uveal Melanoma.Cancers (Basel). 2019 May 29;11(6):751. doi: 10.3390/cancers11060751.
32 Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone.J Biol Chem. 2018 May 25;293(21):8285-8294. doi: 10.1074/jbc.RA118.002316. Epub 2018 Mar 9.
33 Loss of prohibitin induces mitochondrial damages altering -cell function and survival and is responsible for gradual diabetes development.Diabetes. 2013 Oct;62(10):3488-99. doi: 10.2337/db13-0152. Epub 2013 Jul 17.
34 Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.Autism Res. 2017 Mar;10(3):546-557. doi: 10.1002/aur.1733. Epub 2016 Nov 29.
35 Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus.Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4641-5. doi: 10.1073/pnas.88.11.4641.
36 A novel serine protease SNC19 associated with human colorectal cancer.Chin Med J (Engl). 2001 Jul;114(7):726-30.
37 Prognostic relevance of oxidative stress measurement in chronic lymphocytic leukaemia.Eur J Haematol. 2017 Oct;99(4):306-314. doi: 10.1111/ejh.12918. Epub 2017 Aug 3.
38 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
39 Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
40 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.
41 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
42 Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
43 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.