Details of Drug Off-Target (DOT)

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

• DOT Name: Clustered mitochondria protein homolog (CLUH)
• Gene Name: CLUH
• Related Disease:
  Alzheimer disease
  Head-neck squamous cell carcinoma
• UniProt ID: CLU_HUMAN
• Pfam ID: PF13236 ; PF15044 ; PF12807 ; PF13424
• Sequence:
  MLLNGDCPESLKKEAAAAEPPRENGLDEAGPGDETTGQEVIVIQDTGFSVKILAPGIEPF
  SLQVSPQEMVQEIHQVLMDREDTCHRTCFSLHLDGNVLDHFSELRSVEGLQEGSVLRVVE
  EPYTVREARIHVRHVRDLLKSLDPSDAFNGVDCNSLSFLSVFTDGDLGDSGKRKKGLEMD
  PIDCTPPEYILPGSRERPLCPLQPQNRDWKPLQCLKVLTMSGWNPPPGNRKMHGDLMYLF
  VITAEDRQVSITASTRGFYLNQSTAYHFNPKPASPRFLSHSLVELLNQISPTFKKNFAVL
  QKKRVQRHPFERIATPFQVYSWTAPQAEHAMDCVRAEDAYTSRLGYEEHIPGQTRDWNEE
  LQTTRELPRKNLPERLLRERAIFKVHSDFTAAATRGAMAVIDGNVMAINPSEETKMQMFI
  WNNIFFSLGFDVRDHYKDFGGDVAAYVAPTNDLNGVRTYNAVDVEGLYTLGTVVVDYRGY
  RVTAQSIIPGILERDQEQSVIYGSIDFGKTVVSHPRYLELLERTSRPLKILRHQVLNDRD
  EEVELCSSVECKGIIGNDGRHYILDLLRTFPPDLNFLPVPGEELPEECARAGFPRAHRHK
  LCCLRQELVDAFVEHRYLLFMKLAALQLMQQNASQLETPSSLENGGPSSLESKSEDPPGQ
  EAGSEEEGSSASGLAKVKELAETIAADDGTDPRSREVIRNACKAVGSISSTAFDIRFNPD
  IFSPGVRFPESCQDEVRDQKQLLKDAAAFLLSCQIPGLVKDCMEHAVLPVDGATLAEVMR
  QRGINMRYLGKVLELVLRSPARHQLDHVFKIGIGELITRSAKHIFKTYLQGVELSGLSAA
  ISHFLNCFLSSYPNPVAHLPADELVSKKRNKRRKNRPPGAADNTAWAVMTPQELWKNICQ
  EAKNYFDFDLECETVDQAVETYGLQKITLLREISLKTGIQVLLKEYSFDSRHKPAFTEED
  VLNIFPVVKHVNPKASDAFHFFQSGQAKVQQGFLKEGCELINEALNLFNNVYGAMHVETC
  ACLRLLARLHYIMGDYAEALSNQQKAVLMSERVMGTEHPNTIQEYMHLALYCFASSQLST
  ALSLLYRARYLMLLVFGEDHPEMALLDNNIGLVLHGVMEYDLSLRFLENALAVSTKYHGP
  KALKVALSHHLVARVYESKAEFRSALQHEKEGYTIYKTQLGEDHEKTKESSEYLKCLTQQ
  AVALQRTMNEIYRNGSSANIPPLKFTAPSMASVLEQLNVINGILFIPLSQKDLENLKAEV
  ARRHQLQEASRNRDRAEEPMATEPAPAGAPGDLGSQPPAAKDPSPSVQG
• Function: mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria. Specifically binds mRNAs of nuclear-encoded mitochondrial proteins in the cytoplasm and regulates transport or translation of these transcripts close to mitochondria, playing a role in mitochondrial biogenesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[2]

10 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 Clustered mitochondria protein homolog (CLUH).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Clustered mitochondria protein homolog (CLUH).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Clustered mitochondria protein homolog (CLUH).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Clustered mitochondria protein homolog (CLUH).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Clustered mitochondria protein homolog (CLUH).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Clustered mitochondria protein homolog (CLUH).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Clustered mitochondria protein homolog (CLUH).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Clustered mitochondria protein homolog (CLUH).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Clustered mitochondria protein homolog (CLUH).	[9]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Clustered mitochondria protein homolog (CLUH).	[14]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Clustered mitochondria protein homolog (CLUH).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Clustered mitochondria protein homolog (CLUH).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Clustered mitochondria protein homolog (CLUH).	[13]

References

• [1] Genetics of clusterin isoform expression and Alzheimer's disease risk.PLoS One. 2012;7(4):e33923. doi: 10.1371/journal.pone.0033923. Epub 2012 Apr 10.
• [2] Clusterin is a gene-specific target of microRNA-21 in head and neck squamous cell carcinoma. Clin Cancer Res. 2014 Feb 15;20(4):868-77.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] 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.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] 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.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells. Arch Toxicol. 2023 Jan;97(1):217-233. doi: 10.1007/s00204-022-03375-2. Epub 2022 Oct 10.