Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGEO1LP)

DOT Name Minor histocompatibility antigen H13 (HM13)
Synonyms EC 3.4.23.-; Intramembrane protease 1; IMP-1; IMPAS-1; hIMP1; Presenilin-like protein 3; Signal peptide peptidase
Gene Name HM13
Related Disease
Mycoses ( )
Advanced cancer ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Disorder of orbital region ( )
Epithelial neoplasm ( )
Epithelial ovarian cancer ( )
Fatty liver disease ( )
Hepatitis C virus infection ( )
Herpes simplex infection ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Urinary tract infection ( )
Choriocarcinoma ( )
Metastatic malignant neoplasm ( )
Adult glioblastoma ( )
Bacterial vaginosis ( )
Conjunctivitis ( )
Cystitis ( )
Ebola virus infection ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Leishmaniasis ( )
Malaria ( )
Melanoma ( )
Mycosis fungoides ( )
Primary cutaneous T-cell lymphoma ( )
Sezary syndrome ( )
Stomach cancer ( )
Toxoplasmosis ( )
UniProt ID
HM13_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.4.23.-
Pfam ID
PF04258
Sequence
MDSALSDPHNGSAEAGGPTNSTTRPPSTPEGIALAYGSLLLMALLPIFFGALRSVRCARG
KNASDMPETITSRDAARFPIIASCTLLGLYLFFKIFSQEYINLLLSMYFFVLGILALSHT
ISPFMNKFFPASFPNRQYQLLFTQGSGENKEEIINYEFDTKDLVCLGLSSIVGVWYLLRK
HWIANNLFGLAFSLNGVELLHLNNVSTGCILLGGLFIYDVFWVFGTNVMVTVAKSFEAPI
KLVFPQDLLEKGLEANNFAMLGLGDVVIPGIFIALLLRFDISLKKNTHTYFYTSFAAYIF
GLGLTIFIMHIFKHAQPALLYLVPACIGFPVLVALAKGEVTEMFSYEESNPKDPAAVTES
KEGTEASASKGLEKKEK
Function
Catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides. May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein. Involved in the intramembrane cleavage of the integral membrane protein PSEN1. Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner. May play a role in graft rejection.
Tissue Specificity
Widely expressed with highest levels in kidney, liver, placenta, lung, leukocytes and small intestine and reduced expression in heart and skeletal muscle. Expressed abundantly in the CNS with highest levels in thalamus and medulla.
Reactome Pathway
Regulation of HMOX1 expression and activity (R-HSA-9707587 )

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mycoses DIS9K7PB Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Autoimmune disease DISORMTM Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Altered Expression [4]
Breast carcinoma DIS2UE88 Strong Altered Expression [4]
Breast neoplasm DISNGJLM Strong Altered Expression [5]
Colon cancer DISVC52G Strong Biomarker [6]
Colon carcinoma DISJYKUO Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [7]
Disorder of orbital region DISH0ECJ Strong Biomarker [8]
Epithelial neoplasm DIS0T594 Strong Biomarker [9]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [10]
Fatty liver disease DIS485QZ Strong Altered Expression [11]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [12]
Herpes simplex infection DISL1SAV Strong Biomarker [8]
Lung cancer DISCM4YA Strong Altered Expression [13]
Lung carcinoma DISTR26C Strong Altered Expression [13]
Neoplasm DISZKGEW Strong Biomarker [9]
Ovarian cancer DISZJHAP Strong Biomarker [10]
Ovarian neoplasm DISEAFTY Strong Biomarker [10]
Urinary tract infection DISMT6UV Strong Biomarker [14]
Choriocarcinoma DISDBVNL moderate Altered Expression [15]
Metastatic malignant neoplasm DIS86UK6 Disputed Altered Expression [2]
Adult glioblastoma DISVP4LU Limited Biomarker [16]
Bacterial vaginosis DISK2MZ2 Limited Biomarker [17]
Conjunctivitis DISGOZ4P Limited Biomarker [18]
Cystitis DIS2D4B9 Limited Biomarker [18]
Ebola virus infection DISJAVM1 Limited Biomarker [19]
Gastric cancer DISXGOUK Limited Genetic Variation [20]
Glioblastoma multiforme DISK8246 Limited Altered Expression [16]
Leishmaniasis DISABTW7 Limited Biomarker [21]
Malaria DISQ9Y50 Limited Biomarker [22]
Melanoma DIS1RRCY Limited Altered Expression [23]
Mycosis fungoides DIS62RB8 Limited Biomarker [24]
Primary cutaneous T-cell lymphoma DIS35WVW Limited Biomarker [24]
Sezary syndrome DISFMTC7 Limited Biomarker [24]
Stomach cancer DISKIJSX Limited Genetic Variation [20]
Toxoplasmosis DISYP8FH Limited Biomarker [25]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Minor histocompatibility antigen H13 (HM13). [26]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Minor histocompatibility antigen H13 (HM13). [27]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Minor histocompatibility antigen H13 (HM13). [28]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Minor histocompatibility antigen H13 (HM13). [29]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Minor histocompatibility antigen H13 (HM13). [30]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Minor histocompatibility antigen H13 (HM13). [31]
Fluorouracil DMUM7HZ Approved Fluorouracil affects the expression of Minor histocompatibility antigen H13 (HM13). [32]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Minor histocompatibility antigen H13 (HM13). [33]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Minor histocompatibility antigen H13 (HM13). [29]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Minor histocompatibility antigen H13 (HM13). [36]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Minor histocompatibility antigen H13 (HM13). [37]
CH-223191 DMMJZYC Investigative CH-223191 increases the expression of Minor histocompatibility antigen H13 (HM13). [39]
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⏷ Show the Full List of 12 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Minor histocompatibility antigen H13 (HM13). [34]
Glyphosate DM0AFY7 Investigative Glyphosate affects the methylation of Minor histocompatibility antigen H13 (HM13). [38]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 affects the binding of Minor histocompatibility antigen H13 (HM13). [35]
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References

1 Molecular and epidemiological analysis of IMP-1 metallo--lactamase-producing Klebsiella pneumoniae in a tertiary care hospital in Japan.J Infect Chemother. 2019 Apr;25(4):240-246. doi: 10.1016/j.jiac.2018.11.012. Epub 2019 Jan 2.
2 IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.Nucleic Acids Res. 2019 May 7;47(8):4334-4348. doi: 10.1093/nar/gkz136.
3 Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?.Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2169-2182. doi: 10.1016/j.bbamcr.2017.06.007. Epub 2017 Jun 15.
4 Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation.Oncogene. 2019 Mar;38(10):1688-1701. doi: 10.1038/s41388-018-0539-y. Epub 2018 Oct 22.
5 IMP3 promotes TNBC stem cell property through miRNA-34a regulation.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2688-2696. doi: 10.26355/eurrev_201805_14965.
6 IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2.Cancer Res. 2011 Mar 15;71(6):2172-82. doi: 10.1158/0008-5472.CAN-10-3295. Epub 2011 Jan 20.
7 IMP1 3' UTR shortening enhances metastatic burden in colorectal cancer.Carcinogenesis. 2019 Jun 10;40(4):569-579. doi: 10.1093/carcin/bgy153.
8 Absence of Signal Peptide Peptidase, an Essential Herpes Simplex Virus 1 Glycoprotein K Binding Partner, Reduces Virus Infectivity In Vivo.J Virol. 2019 Nov 13;93(23):e01309-19. doi: 10.1128/JVI.01309-19. Print 2019 Dec 1.
9 Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon.Mol Cancer Res. 2015 Nov;13(11):1478-86. doi: 10.1158/1541-7786.MCR-15-0224. Epub 2015 Jul 20.
10 Humoral autoimmune responses to insulin-like growth factor II mRNA-binding proteins IMP1 and p62/IMP2 in ovarian cancer.J Immunol Res. 2014;2014:326593. doi: 10.1155/2014/326593. Epub 2014 Apr 27.
11 TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis.Nat Commun. 2016 May 4;7:11379. doi: 10.1038/ncomms11379.
12 The potential of signal peptide peptidase as a therapeutic target for hepatitis C.Expert Opin Ther Targets. 2017 Sep;21(9):827-836. doi: 10.1080/14728222.2017.1369959. Epub 2017 Aug 22.
13 A Novel IMP1 Inhibitor, BTYNB, Targets c-Myc and Inhibits Melanoma and Ovarian Cancer Cell Proliferation.Transl Oncol. 2017 Oct;10(5):818-827. doi: 10.1016/j.tranon.2017.07.008. Epub 2017 Aug 29.
14 Detection of VIM-1 and IMP-1 genes in Klebsiella pneumoniae and relationship with biofilm formation.Microb Pathog. 2018 Feb;115:25-30. doi: 10.1016/j.micpath.2017.12.036. Epub 2017 Dec 14.
15 IMP1 promotes choriocarcinoma cell migration and invasion through the novel effectors RSK2 and PPME1.Gynecol Oncol. 2013 Oct;131(1):182-90. doi: 10.1016/j.ygyno.2013.07.106. Epub 2013 Aug 1.
16 Signal Peptide Peptidase, Encoded by HM13, Contributes to Tumor Progression by Affecting EGFRvIII Secretion Profiles in Glioblastoma.CNS Neurosci Ther. 2017 Mar;23(3):257-265. doi: 10.1111/cns.12672.
17 Prospective Evaluation of Molecular Assays for Diagnosis of Vaginitis.J Clin Microbiol. 2019 Dec 23;58(1):e01264-19. doi: 10.1128/JCM.01264-19. Print 2019 Dec 23.
18 Analysis of IMP-1 type metallo--lactamase-producing Acinetobacter radioresistens isolated from companion animals.J Infect Chemother. 2017 Sep;23(9):655-657. doi: 10.1016/j.jiac.2017.03.011. Epub 2017 Apr 10.
19 Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins.PLoS One. 2019 Apr 11;14(4):e0214968. doi: 10.1371/journal.pone.0214968. eCollection 2019.
20 SPP1 rs4754 and its epistatic interactions with SPARC polymorphisms in gastric cancer susceptibility.Gene. 2018 Jan 15;640:43-50. doi: 10.1016/j.gene.2017.09.053. Epub 2017 Sep 28.
21 Understanding serine proteases implications on Leishmania spp lifecycle.Exp Parasitol. 2018 Jan;184:67-81. doi: 10.1016/j.exppara.2017.11.008. Epub 2017 Nov 22.
22 Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria.Biochem Biophys Res Commun. 2009 Mar 13;380(3):454-9. doi: 10.1016/j.bbrc.2009.01.083. Epub 2009 Jan 25.
23 Protein kinase C- is upregulated by IMP1 in melanoma and is linked to poor survival.Melanoma Res. 2019 Oct;29(5):539-543. doi: 10.1097/CMR.0000000000000558.
24 Expression of cancer/testis antigens in cutaneous T cell lymphomas.Int J Cancer. 2002 Feb 10;97(5):668-70. doi: 10.1002/ijc.1643.
25 Toxoplasma gondii immune mapped protein-1 (TgIMP1) is a novel vaccine candidate against toxoplasmosis.Vaccine. 2012 Mar 16;30(13):2282-7. doi: 10.1016/j.vaccine.2012.01.073. Epub 2012 Feb 3.
26 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
27 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.
28 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
29 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
30 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.
31 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
32 Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
33 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
34 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.
35 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
36 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
37 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
38 Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.
39 Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.