Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT1VKEF)

• DOT Name: IQ motif and ubiquitin-like domain-containing protein (IQUB)
• Gene Name: IQUB
• Related Disease:
  Breast cancer
  Breast carcinoma
  Acute myelogenous leukaemia
• UniProt ID: IQUB_HUMAN
• PDB ID: 2DAF; 8J07
• Pfam ID: PF00240
• Sequence:
  MSNQQEKYEAQNIVNSTEESDDAFDTVTIPVPSEEPQESDQTEEHESGIEQFSESHAIHV
  EEQSDQSFSSLEPDNEQLMEEVISPRQVSYTPQHHEKQYAMQRPNDDSLAFLDKIKSVKE
  SLQESVEDSLATVKVVLIPVGQEIVIPFKVDTILKYLKDHFSHLLGIPHSVLQIRYSGKI
  LKNNETLVQHGVKPQEIVQVEIFSTNPDLYPVRRIDGLTDVSQIITVTVQTGLDQYQQVP
  VEIVKSDFHKPFLGGFRHKVTGVEYHNAGTQTVPKRIPERLSIFCRDTQTVFQKKNLQQT
  TNTTSTQMTNIGVYVSNMTDKLVTPGKYFSAAEYHAQRLKAVIVIQTYYRQWHAKIFVEN
  LRRQKSLRLEWETQQELRKIREKEEWIKLDYHRRHNPKTNEDFEFLYNALEFWRQEELTR
  INQSFTGAERKAALCELLEKETQIIASIGRHRYIAYMANQEAAIQAFLDKCSAPKIWRTP
  NGKTIEMDTQFTIRARELQNIYKCIMLKNISQDERLDVLLTLKHTVKEHECKLTQEILEL
  IDREVDLMMRGVKHHNLEGLRKRIATLFFHYIKTPLFNPEVAKYLKVPQDPLKFYKKIYF
  CHSCQLYLPSTEFSVSSTSRRIYRCRNCINLQNEAQKRESFLKYKCLLQQLYYTEADYED
  DSKIAFLMQLQDIQYLTENIWASQSVLSACDNLSDLVMVRWNKSLEWSPWNCILLTKDEA
  AAHLKLTSIEEGYERSFIHKIKHKHILAKNYFSQVPVLASFILDDGEIDEIRWKYHSDTT
  PKIIESQRPPH
• Function: Adapter protein that anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes. The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum. May play a role in inhibiting signaling via MAPK1/ERK2 and MAPK3/ERK1. Additionally, may play a role in the functioning of cilia. Not required for the functioning of tracheal or ependymal cilia.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

1 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 IQ motif and ubiquitin-like domain-containing protein (IQUB).	[3]

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 IQ motif and ubiquitin-like domain-containing protein (IQUB).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of IQ motif and ubiquitin-like domain-containing protein (IQUB).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of IQ motif and ubiquitin-like domain-containing protein (IQUB).	[6]

References

• [1] Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3/-catenin signaling pathway in breast cancer.Cancer Med. 2018 Aug;7(8):3875-3888. doi: 10.1002/cam4.1568. Epub 2018 Jul 2.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] 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.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.