Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT30GD05)

DOT Name Pyrin and HIN domain-containing protein 1 (PYHIN1)
Synonyms Interferon-inducible protein X
Gene Name PYHIN1
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Herpes simplex infection ( )
Prostate cancer ( )
Prostate neoplasm ( )
Tuberculosis ( )
Asthma ( )
UniProt ID
IFIX_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02760 ; PF02758
Sequence
MANNYKKIVLLKGLEVINDYHFRIVKSLLSNDLKLNPKMKEEYDKIQIADLMEEKFPGDA
GLGKLIEFFKEIPTLGDLAETLKREKLKVANKIESIPVKGIIPSKKTKQKEVYPATPACT
PSNRLTAKGAEETLGPQKRKKPSEEETGTKRSKMSKEQTRPSCSAGASTSTAMGRSPPPQ
TSSSAPPNTSSTESLKPLANRHATASKNIFREDPIIAMVLNATKVFKYESSENEQRRMFH
ATVATQTQFFHVKVLNINLKRKFIKKRIIIISNYSKRNSLLEVNEASSVSEAGPDQTFEV
PKDIIRRAKKIPKINILHKQTSGYIVYGLFMLHTKIVNRKTTIYEIQDKTGSMAVVGKGE
CHNIPCEKGDKLRLFCFRLRKRENMSKLMSEMHSFIQIQKNTNQRSHDSRSMALPQEQSQ
HPKPSEASTTLPESHLKTPQMPPTTPSSSSFTKKDETHPGAQSSPANFRITSPTVAPPLS
SDTSTNRHPAVP
Function
Major mediator of the tumor suppressor activity of IFN in breast cancer cells. Promotes ubiquitination and subsequent degradation of MDM2, which leads to p53/TP53 stabilization. Promotes ubiquitination and subsequent degradation of HDAC1, which in turn enhances maspin expression, and impairs invasive activity of cancer cells.
Tissue Specificity Expressed in spleen, lymph node and peripheral blood leukocytes, and at lower levels in thymus, bone marrow and fetal liver. Down-regulated in breast tumors.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Breast neoplasm DISNGJLM Strong Altered Expression [2]
Herpes simplex infection DISL1SAV Strong Biomarker [3]
Prostate cancer DISF190Y Strong Biomarker [4]
Prostate neoplasm DISHDKGQ Strong Biomarker [4]
Tuberculosis DIS2YIMD Strong Genetic Variation [5]
Asthma DISW9QNS moderate Biomarker [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Pyrin and HIN domain-containing protein 1 (PYHIN1). [7]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Pyrin and HIN domain-containing protein 1 (PYHIN1). [8]
DNCB DMDTVYC Phase 2 DNCB decreases the expression of Pyrin and HIN domain-containing protein 1 (PYHIN1). [9]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Pyrin and HIN domain-containing protein 1 (PYHIN1). [11]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Pyrin and HIN domain-containing protein 1 (PYHIN1). [12]
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1 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 increases the methylation of Pyrin and HIN domain-containing protein 1 (PYHIN1). [10]
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References

1 Antitumor activity of IFIX, a novel interferon-inducible HIN-200 gene, in breast cancer.Oncogene. 2004 Jun 3;23(26):4556-66. doi: 10.1038/sj.onc.1207592.
2 Interferon-inducible protein IFIXalpha inhibits cell invasion by upregulating the metastasis suppressor maspin.Mol Carcinog. 2008 Oct;47(10):739-43. doi: 10.1002/mc.20423.
3 Human Antiviral Protein IFIX Suppresses Viral Gene Expression during Herpes Simplex Virus 1 (HSV-1) Infection and Is Counteracted by Virus-induced Proteasomal Degradation.Mol Cell Proteomics. 2017 Apr;16(4 suppl 1):S200-S214. doi: 10.1074/mcp.M116.064741. Epub 2017 Jan 11.
4 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
5 Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil.Int J Infect Dis. 2020 Mar;92:21-28. doi: 10.1016/j.ijid.2019.12.013. Epub 2019 Dec 13.
6 Exome analysis of patients with concurrent pediatric inflammatory bowel disease and autoimmune disease.Inflamm Bowel Dis. 2015 Jun;21(6):1229-36. doi: 10.1097/MIB.0000000000000381.
7 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
8 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
9 Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
10 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.
11 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
12 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.