Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9Q95J5)

• DOT Name: Armadillo repeat-containing X-linked protein 2 (ARMCX2)
• Synonyms: ARM protein lost in epithelial cancers on chromosome X 2; Protein ALEX2
• Gene Name: ARMCX2
• Related Disease:
  Carcinoma
  Ovarian cancer
• UniProt ID: ARMX2_HUMAN
• Pfam ID: PF04826
• Sequence:
  MSRVRDAGCVAAGIVIGAGAWYCVYKYTRGRDQTKKRMAKPKNRAVAGTGARARAGLRAG
  FTIDLGSGFSPPTPVRAEAEDRAQDEASALDTVGAEAVAPAASSAEAQSGAGSQAQEADG
  AGVGPKAESVVGAAMASAIAPPPGVTEALGAAEAPAMAGAPKVAEAPREAETSRAAVPPG
  TVVPTEAAAPTEVTEGPGVAAPTKVAEAPGVASPTEAAEAPVPATPTGAAAPTGAAESPG
  TSGSPRTAVVPGTSAAKKATPGAHTGAIPKATSATGAVPKGGGKGVTRSRNGGKGKGKKS
  KVEVDELGMGFRPGDGAAAAAAASANGGQAFLAEVPDSEEGESGWTDTESDSDSEPETQR
  RGRGRRPVAMQKRPFPYEIDEILGVRDLRKVLALLQKSDDPFIQQVALLTLSNNANYSCN
  QETIRKLGGLPIIANMINKTDPHIKEKALMAMNNLSENYENQGRLQVYMNKVMDDIMASN
  LNSAVQVVGLKFLTNMTITNDYQHLLVNSIANFFRLLSQGGGKIKVEILKILSNFAENPD
  MLKKLLSTQVPASFSSLYNSYVESEILINALTLFEIIYDNLRAEVFNYREFNKGSLFYLC
  TTSGVCVKKIRALANHHDLLVKVKVIKLVNKF
• Function: May regulate the dynamics and distribution of mitochondria in neural cells.
• 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 expressed in pancreas and ovarian carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Armadillo repeat-containing X-linked protein 2 (ARMCX2) affects the response to substance of Cisplatin.	[9]

3 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 Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Armadillo repeat-containing X-linked protein 2 (ARMCX2).	[7]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.