Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DD5EW)

• DOT Name: Calmodulin-like protein 4 (CALML4)
• Synonyms: Serologically defined breast cancer antigen NY-BR-20
• Gene Name: CALML4
• UniProt ID: CALL4_HUMAN
• Pfam ID: PF13499
• Sequence:
  MAAEHLLPGPPPSLADFRLEAGGKGTERGSGSSKPTGSSRGPRMAKFLSQDQINEYKECF
  SLYDKQQRGKIKATDLMVAMRCLGASPTPGEVQRHLQTHGIDGNGELDFSTFLTIMHMQI
  KQEDPKKEILLAMLMVDKEKKGYVMASDLRSKLTSLGEKLTHKEVDDLFREADIEPNGKV
  KYDEFIHKITLPGRDY
• Function: As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. Acts as a light chain for MYO7B and is required for efficient targeting of the IMAC to the tips of border brush microvilli.
• Tissue Specificity: .Expressed in the intestinal tract.; [Isoform 6]: Dominant transcript in the intestinal tract.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Phosphatidylinositol sig.ling system (hsa04070)
  Oocyte meiosis (hsa04114)
  Cellular senescence (hsa04218)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Apelin sig.ling pathway (hsa04371)
  C-type lectin receptor sig.ling pathway (hsa04625)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Neurotrophin sig.ling pathway (hsa04722)
  Dopaminergic sy.pse (hsa04728)
  Olfactory transduction (hsa04740)
  Phototransduction (hsa04744)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Insulin sig.ling pathway (hsa04910)
  GnRH sig.ling pathway (hsa04912)
  Estrogen sig.ling pathway (hsa04915)
  Melanogenesis (hsa04916)
  Oxytocin sig.ling pathway (hsa04921)
  Glucagon sig.ling pathway (hsa04922)
  Renin secretion (hsa04924)
  Aldosterone synthesis and secretion (hsa04925)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
  Pertussis (hsa05133)
  Tuberculosis (hsa05152)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Glioma (hsa05214)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calmodulin-like protein 4 (CALML4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calmodulin-like protein 4 (CALML4).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Calmodulin-like protein 4 (CALML4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calmodulin-like protein 4 (CALML4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Calmodulin-like protein 4 (CALML4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calmodulin-like protein 4 (CALML4).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calmodulin-like protein 4 (CALML4).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Calmodulin-like protein 4 (CALML4).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Calmodulin-like protein 4 (CALML4).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Calmodulin-like protein 4 (CALML4).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Calmodulin-like protein 4 (CALML4).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Calmodulin-like protein 4 (CALML4).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Calmodulin-like protein 4 (CALML4).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Calmodulin-like protein 4 (CALML4).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Calmodulin-like protein 4 (CALML4).	[11]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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.