Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUDD0QT)

• DOT Name: Actin-like protein 8 (ACTL8)
• Synonyms: Cancer/testis antigen 57; CT57
• Gene Name: ACTL8
• Related Disease:
  Colorectal carcinoma
  Glioblastoma multiforme
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Head-neck squamous cell carcinoma
  Testicular cancer
  Advanced cancer
• UniProt ID: ACTL8_HUMAN
• Pfam ID: PF00022
• Sequence:
  MAARTVIIDHGSGFLKAGTAGWNEPQMVFPNIVNYLPCKENPGPSYARRRVSLGIDICHP
  DTFSYPIERGRILNWEGVQYLWSFVLENHRREQEVPPVIITETPLREPADRKKMLEILFE
  LLHVPSVLLADQLQMSLYASGLLTGVVVDSGYGLTRVQPFHQGRPLPASGKTLEFAGQDL
  SAYLLKSLFKEDCDRRCLFQLETVAVTQMNKCYVPQNLGEALDFRERQQSALDESNTYQL
  PDGSRVELTPMQRVAPEMFFSPQVFEQPGPSIPRAIVESVESCEISLRPLLVSHVMACGG
  NTLYPGFTKRLFRELMGDHVSSTKATVWEGSNRNFSVWLGASVVAHLSTYQSEWMSREEY
  GEHMRM
• Tissue Specificity: Strongly expressed in testis and pancreas. Weak expression in placenta.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[2]
Testicular cancer	DIS6HNYO	moderate	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]

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 Actin-like protein 8 (ACTL8).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Actin-like protein 8 (ACTL8).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Actin-like protein 8 (ACTL8).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Actin-like protein 8 (ACTL8).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Actin-like protein 8 (ACTL8).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Actin-like protein 8 (ACTL8).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Actin-like protein 8 (ACTL8).	[9]

References

• [1] Upregulated expression of ACTL8 contributes to invasion and metastasis and indicates poor prognosis in colorectal cancer.Onco Targets Ther. 2019 Mar 1;12:1749-1763. doi: 10.2147/OTT.S185858. eCollection 2019.
• [2] High expression of ACTL8 is poor prognosis and accelerates cell progression in head and neck squamous cell carcinoma.Mol Med Rep. 2019 Feb;19(2):877-884. doi: 10.3892/mmr.2018.9716. Epub 2018 Dec 3.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.