Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM8DNQU)

• DOT Name: Calmodulin-like protein 3 (CALML3)
• Synonyms: CaM-like protein; CLP; Calmodulin-related protein NB-1
• Gene Name: CALML3
• Related Disease:
  Isolated Pierre-Robin syndrome
  Acute myocardial infarction
  Autoimmune disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cleft soft palate
  Colitis
  Colon cancer
  Colon carcinoma
  Glioma
  Lung cancer
  Lung neoplasm
  Obstructive lung disease
  Oral lichen planus
  Osteosarcoma
  Triple negative breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Dental caries
  Hepatocellular carcinoma
  Liver cancer
• UniProt ID: CALL3_HUMAN
• PDB ID: 1GGZ
• Pfam ID: PF13499
• Sequence:
  MADQLTEEQVTEFKEAFSLFDKDGDGCITTRELGTVMRSLGQNPTEAELRDMMSEIDRDG
  NGTVDFPEFLGMMARKMKDTDNEEEIREAFRVFDKDGNGFVSAAELRHVMTRLGEKLSDE
  EVDEMIRAADTDGDGQVNYEEFVRVLVSK
• Function: May function as a specific light chain of unconventional myosin-10 (MYO10), also enhances MYO10 translation, possibly by acting as a chaperone for the emerging MYO10 heavy chain protein. May compete with calmodulin by binding, with different affinities, to cellular substrates.
• Tissue Specificity: Expressed in normal mammary, prostate, cervical, and epidermal tissues. It is greatly reduced or undetectable in transformed cells.
• 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

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated Pierre-Robin syndrome	DISVEHG7	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cleft soft palate	DISCN11I	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung neoplasm	DISVARNB	Strong	Biomarker	[10]
Obstructive lung disease	DIS4IIDZ	Strong	Biomarker	[11]
Oral lichen planus	DISVEAJA	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[12]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[13]
Dental caries	DISRBCMD	Limited	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[13]
Liver cancer	DISDE4BI	Limited	Biomarker	[13]

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 3 (CALML3).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calmodulin-like protein 3 (CALML3).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Calmodulin-like protein 3 (CALML3).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Calmodulin-like protein 3 (CALML3).	[17]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Calmodulin-like protein 3 (CALML3).	[18]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Calmodulin-like protein 3 (CALML3).	[19]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Calmodulin-like protein 3 (CALML3).	[20]

References

• [1] Pathogenesis of Cleft Palate in Robin Sequence: Observations From Prenatal Magnetic Resonance Imaging.J Oral Maxillofac Surg. 2018 May;76(5):1058-1064. doi: 10.1016/j.joms.2017.10.006. Epub 2017 Oct 16.
• [2] Identification of Transcription Factor-Gene Regulatory Network in Acute Myocardial Infarction.Heart Lung Circ. 2017 Apr;26(4):343-353. doi: 10.1016/j.hlc.2016.06.1209. Epub 2016 Jul 26.
• [3] Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral lichen planus.J Eur Acad Dermatol Venereol. 2017 May;31(5):880-886. doi: 10.1111/jdv.13989. Epub 2016 Oct 21.
• [4] The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line.Int J Oncol. 2007 Oct;31(4):915-22.
• [5] Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGF signaling.Oncogene. 2018 Jan 18;37(3):323-331. doi: 10.1038/onc.2017.342. Epub 2017 Sep 18.
• [6] A Comparative Study of Oral Microbiota in Infants with Complete Cleft Lip and Palate or Cleft Soft Palate.Biomed Res Int. 2017;2017:1460243. doi: 10.1155/2017/1460243. Epub 2017 Mar 14.
• [7] Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis.PLoS One. 2017 Apr 24;12(4):e0175935. doi: 10.1371/journal.pone.0175935. eCollection 2017.
• [8] Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma.Drug Deliv. 2018 Nov;25(1):1718-1727. doi: 10.1080/10717544.2018.1494225.
• [9] Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents.Oncotarget. 2017 Mar 21;8(12):18885-18900. doi: 10.18632/oncotarget.13806.
• [10] Selective Cell Penetrating Peptide-Functionalized Envelope-Type Chimeric Lipopepsomes Boost Systemic RNAi Therapy for Lung Tumors.Adv Healthc Mater. 2019 Aug;8(16):e1900500. doi: 10.1002/adhm.201900500. Epub 2019 Jun 24.
• [11] An algorithm for predicting Robin sequence from fetal MRI.Prenat Diagn. 2018 Apr;38(5):357-364. doi: 10.1002/pd.5239. Epub 2018 Mar 13.
• [12] Marine natural compound cyclo(L-leucyl-L-prolyl) peptide inhibits migration of triple negative breast cancer cells by disrupting interaction of CD151 and EGFR signaling.Chem Biol Interact. 2020 Jan 5;315:108872. doi: 10.1016/j.cbi.2019.108872. Epub 2019 Oct 24.
• [13] Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma.Nat Commun. 2018 Feb 14;9(1):678. doi: 10.1038/s41467-018-03024-2.
• [14] Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159.Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00776-17. doi: 10.1128/AAC.00776-17. Print 2017 Aug.
• [15] 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.
• [16] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [19] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [20] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [21] 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.