Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIX9V3E)

• DOT Name: Dynein regulatory complex protein 9 (IQCG)
• Synonyms: IQ domain-containing protein G
• Gene Name: IQCG
• Related Disease:
  Diamond-Blackfan anemia 5
  Myeloid leukaemia
• UniProt ID: DRC9_HUMAN
• PDB ID: 4LZX; 4M1L; 8J07
• Pfam ID: PF00612
• Sequence:
  MEEDSLEDSNLPPKVWHSEMTVSVTGEPPSTVEEEGIPKETDIEIIPEIPETLEPLSLPD
  VLRISAVLEDTTDQLSILNYIMPVQYEGRQSICVKSREMNLEGTNLDKLPMASTITKIPS
  PLITEEGPNLPEIRHRGRFAVEFNKMQDLVFKKPTRQTIMTTETLKKIQIDRQFFSDVIA
  DTIKELQDSATYNSLLQALSKERENKMHFYDIIAREEKGRKQIISLQKQLINVKKEWQFE
  VQSQNEYIANLKDQLQEMKAKSNLENRYMKTNTELQIAQTQKKCNRTEELLVEEIEKLRM
  KTEEEARTHTEIEMFLRKEQQKLEERLEFWMEKYDKDTEMKQNELNALKATKASDLAHLQ
  DLAKMIREYEQVIIEDRIEKERSKKKVKQDLLELKSVIKLQAWWRGTMIRREIGGFKMPK
  DKVDSKDSKGKGKGKDKRRGKKK
• Function: Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Binds calmodulin when cellular Ca(2+) levels are low and thereby contributes to the regulation of calcium and calmodulin-dependent protein kinase IV (CAMK4) activity; contributes to the regulation of CAMK4 signaling cascades. Required for normal axoneme assembly in sperm flagella, normal sperm tail formation and for male fertility.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diamond-Blackfan anemia 5	DIS0QY3J	Strong	CausalMutation	[1]
Myeloid leukaemia	DISMN944	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Dynein regulatory complex protein 9 (IQCG).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dynein regulatory complex protein 9 (IQCG).	[10]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dynein regulatory complex protein 9 (IQCG).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dynein regulatory complex protein 9 (IQCG).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dynein regulatory complex protein 9 (IQCG).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Dynein regulatory complex protein 9 (IQCG).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dynein regulatory complex protein 9 (IQCG).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dynein regulatory complex protein 9 (IQCG).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dynein regulatory complex protein 9 (IQCG).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Dynein regulatory complex protein 9 (IQCG).	[12]

References

• [1] Clinical and genomic heterogeneity of Diamond Blackfan anemia in the Russian Federation. Pediatr Blood Cancer. 2015 Sep;62(9):1597-600. doi: 10.1002/pbc.25534. Epub 2015 May 6.
• [2] A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation.Oncogene. 2008 May 29;27(24):3414-23. doi: 10.1038/sj.onc.1210999. Epub 2007 Dec 17.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.