Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTECWJ0Y)

• DOT Name: Endogenous retroviral envelope protein HEMO (ERVMER34-1)
• Synonyms: Endogenous retrovirus group MER34 member 1 Env polyprotein; HERV-MER_4q12 provirus ancestral Env polyprotein; Human endogenous MER34 (medium-reiteration-frequency-family-34) open reading frame; Human endogenous MER34 ORF; HEMO
• Gene Name: ERVMER34-1
• Related Disease: Autism spectrum disorder
• UniProt ID: MER34_HUMAN
• Sequence:
  MGSLSNYALLQLTLTAFLTILVQPQHLLAPVFRTLSILTNQSNCWLCEHLDNAEQPELVF
  VPASASTWWTYSGQWMYERVWYPQAEVQNHSTSSYRKVTWHWEASMEAQGLSFAQVRLLE
  GNFSLCVENKNGSGPFLGNIPKQYCNQILWFDSTDGTFMPSIDVTNESRNDDDDTSVCLG
  TRQCSWFAGCTNRTWNSSAVPLIGLPNTQDYKWVDRNSGLTWSGNDTCLYSCQNQTKGLL
  YQLFRNLFCSYGLTEAHGKWRCADASITNDKGHDGHRTPTWWLTGSNLTLSVNNSGLFFL
  CGNGVYKGFPPKWSGRCGLGYLVPSLTRYLTLNASQITNLRSFIHKVTPHRCTQGDTDNP
  PLYCNPKDNSTIRALFPSLGTYDLEKAILNISKAMEQEFSATKQTLEAHQSKVSSLASAS
  RKDHVLDIPTTQRQTACGTVGKQCCLYINYSEEIKSNIQRLHEASENLKNVPLLDWQGIF
  AKVGDWFRSWGYVLLIVLFCLFIFVLIYVRVFRKSRRSLNSQPLNLALSPQQSAQLLVSE
  TSCQVSNRAMKGLTTHQYDTSLL
• Function: Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution.
• Tissue Specificity: Expressed at high level in the placenta and stem cells (at protein level) . Also expressed in the kidney but at a lower level . Endogenous retroviral envelope protein HEMO, secreted form: Present in the blood of pregnant women (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[1]

9 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 Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[7]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Endogenous retroviral envelope protein HEMO (ERVMER34-1).	[10]

References

• [1] Children With Autism Spectrum Disorder and Their Mothers Share Abnormal Expression of Selected Endogenous Retroviruses Families and Cytokines.Front Immunol. 2019 Sep 26;10:2244. doi: 10.3389/fimmu.2019.02244. eCollection 2019.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.