Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6M9MM)

• DOT Name: Armadillo repeat-containing protein 3 (ARMC3)
• Synonyms: Beta-catenin-like protein; Cancer/testis antigen 81; CT81; KU-CT-1
• Gene Name: ARMC3
• Related Disease:
  Systemic lupus erythematosus
  Endometrial carcinoma
  Endometrium neoplasm
  Lung cancer
  Lung carcinoma
• UniProt ID: ARMC3_HUMAN
• Pfam ID: PF00514 ; PF14381
• Sequence:
  MGKKIKKEVEPPPKDVFDPLMIESKKAATVVLMLNSPEEEILAKACEAIYKFALKGEENK
  TTLLELGAVEPLTKLLTHEDKIVRRNATMIFGILASNNDVKKLLRELDVMNSVIAQLAPE
  EEVVIHEFASLCLANMSAEYTSKVQIFEHGGLEPLIRLLSSPDPDVKKNSMECIYNLVQD
  FQCRAKLQELNAIPPILDLLKSEYPVIQLLALKTLGVIANDKESRTMLRDNQGLDHLIKI
  LETKELNDLHIEALAVIANCLEDMDTMVQIQQTGGLKKLLSFAENSTIPDIQKNAAKAIT
  KAAYDPENRKLFHEQEVEKCLVALLGSENDGTKIAASQAISAMCENSGSKDFFNNQGIPQ
  LIQLLKSDNEEVREAAALALANLTTCNPANANAAAEADGIDPLINLLSSKRDGAIANAAT
  VLTNMAMQEPLRLNIQNHDIMHAIISPLRSANTVVQSKAALAVTATACDVEARTELRNSG
  GLEPLVELLRSKNDEVRKHASWAVMVCAGDELTANELCRLGALDILEEVNVSGTRKNKFS
  EAAYNKLLNNNLSLKYSQTGYLSSSNIINDGFYDYGRINPGTKLLPLKELCLQEPSDLRA
  VLLINSKSYVSPPSSMEDKSDVGYGRSISSSSSLRRSSKEKNKKNSYHFSAGFGSPIEDK
  SEPASGRNTVLSKSATKEKGWRKSKGKKEEEKVKEEEEVMVVPKFVGEGSSDKEWCPPSD
  PDFSMYVYEVTKSILPITNIKEQIEDLAKYVAEKMGGKIPKEKLPDFSWELHISELKFQL
  KSNVIPIGHVKKGIFYHRALLFKALADRIGIGCSLVRGEYGRAWNEVMLQNDSRKGVIGG
  LPAPEMYVIDLMFHPGGLMKLRSREADLYRFI
• Function: Essential for male fertility and sperm motility. During spermatogenesis, promotes the autophagic degradation of excessive ribosomes, providing energy resources for mitochondria and thus ensuring sperm flagellar motility.
• Tissue Specificity: .Expressed in skeletal muscle, brain, lung, kidney, prostate and testis.; [Isoform 3]: Mainly expressed in skeletal muscle, liver, spleen and thymus.; [Isoform 5]: Expressed only in the testis among normal tissues but is expressed frequently in various cancer tissues and, particularly, in pancreatic, lung and endometrial cancers.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[1]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[2]
Endometrium neoplasm	DIS6OS2L	Limited	Altered Expression	[2]
Lung cancer	DISCM4YA	Limited	Altered Expression	[2]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[2]

3 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 Armadillo repeat-containing protein 3 (ARMC3).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Armadillo repeat-containing protein 3 (ARMC3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Armadillo repeat-containing protein 3 (ARMC3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Armadillo repeat-containing protein 3 (ARMC3).	[4]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Armadillo repeat-containing protein 3 (ARMC3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Armadillo repeat-containing protein 3 (ARMC3).	[8]

References

• [1] A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.Nat Genet. 2009 Nov;41(11):1228-33. doi: 10.1038/ng.468. Epub 2009 Oct 18.
• [2] A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.Clin Cancer Res. 2006 Jan 1;12(1):191-7. doi: 10.1158/1078-0432.CCR-05-1206.
• [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] 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.
• [5] 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.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.