Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOGL58Z)

• DOT Name: Armadillo repeat-containing X-linked protein 1 (ARMCX1)
• Synonyms: ARM protein lost in epithelial cancers on chromosome X 1; Protein ALEX1
• Gene Name: ARMCX1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Carcinoma
  Ovarian cancer
  Neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: ARMX1_HUMAN
• Pfam ID: PF04826
• Sequence:
  MGRTREAGCVAAGVVIGAGACYCVYRLAWGRDENEKIWDEDEESTDTSEIGVETVKGAKT
  NAGAGSGAKLQGDSEVKPEVSLGLEDCPGVKEKAHSGSHSGGGLEAKAKALFNTLKEQAS
  AKAGKGARVGTISGNRTLAPSLPCPGGRGGGCHPTRSGSRAGGRASGKSKGKARSKSTRA
  PATTWPVRRGKFNFPYKIDDILSAPDLQKVLNILERTNDPFIQEVALVTLGNNAAYSFNQ
  NAIRELGGVPIIAKLIKTKDPIIREKTYNALNNLSVNAENQGKIKTYISQVCDDTMVCRL
  DSAVQMAGLRLLTNMTVTNHYQHLLSYSFPDFFALLFLGNHFTKIQIMKLIINFTENPAM
  TRELVSCKVPSELISLFNKEWDREILLNILTLFENINDNIKNEGLASSRKEFSRSSLFFL
  FKESGVCVKKIKALANHNDLVVKVKVLKVLTKL
• Function: Regulates mitochondrial transport during axon regeneration. Increases the proportion of motile mitochondria by recruiting stationary mitochondria into the motile pool. Enhances mitochondria movement and neurite growth in both adult axons and embryonic neurons. Promotes neuronal survival and axon regeneration after nerve injury. May link mitochondria to the Trak1-kinesin motor complex via its interaction with MIRO1.
• Tissue Specificity: Expressed at high levels ovary, heart, testis, prostate, brain, spleen and colon. Expressed at very low levels in liver and thymus. Not expressed in peripheral blood leukocytes. Not or reduced expressed in lung, prostate, colon, pancreas and ovarian carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[2]
Colorectal neoplasm	DISR1UCN	Definitive	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[4]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[11]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Armadillo repeat-containing X-linked protein 1 (ARMCX1).	[14]

References

• [1] ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells.Asian Pac J Cancer Prev. 2015;16(8):3293-9. doi: 10.7314/apjcp.2015.16.8.3293.
• [2] ALEX1 suppresses colony formation ability of human colorectal carcinoma cell lines.Cancer Sci. 2012 Jul;103(7):1267-71. doi: 10.1111/j.1349-7006.2012.02300.x. Epub 2012 May 17.
• [3] ALEX1, a novel human armadillo repeat protein that is expressed differentially in normal tissues and carcinomas.Biochem Biophys Res Commun. 2001 Jan 12;280(1):340-7. doi: 10.1006/bbrc.2000.4125.
• [4] ALEX1, a novel tumor suppressor gene, inhibits gastric cancer metastasis via the PAR-1/Rho GTPase signaling pathway.J Gastroenterol. 2018 Jan;53(1):71-83. doi: 10.1007/s00535-017-1329-y. Epub 2017 Mar 17.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [13] 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.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] 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.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.