Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0MK3L1)

• DOT Name: Acrosin-binding protein (ACRBP)
• Synonyms: Acrosin-binding protein, 60 kDa form; Cancer/testis antigen 23; CT23; Cancer/testis antigen OY-TES-1; Proacrosin-binding protein sp32
• Gene Name: ACRBP
• Related Disease:
  Advanced cancer
  Colon cancer
  Colorectal adenoma
  Colorectal carcinoma
  Glioma
  Hepatocellular carcinoma
  Juvenile idiopathic arthritis
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Testicular cancer
  Epithelial ovarian cancer
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: ACRBP_HUMAN
• Pfam ID: PF07222
• Sequence:
  MRKPAAGFLPSLLKVLLLPLAPAAAQDSTQASTPGSPLSPTEYERFFALLTPTWKAETTC
  RLRATHGCRNPTLVQLDQYENHGLVPDGAVCSNLPYASWFESFCQFTHYRCSNHVYYAKR
  VLCSQPVSILSPNTLKEIEASAEVSPTTMTSPISPHFTVTERQTFQPWPERLSNNVEELL
  QSSLSLGGQEQAPEHKQEQGVEHRQEPTQEHKQEEGQKQEEQEEEQEEEGKQEEGQGTKE
  GREAVSQLQTDSEPKFHSESLSSNPSSFAPRVREVESTPMIMENIQELIRSAQEIDEMNE
  IYDENSYWRNQNPGSLLQLPHTEALLVLCYSIVENTCIITPTAKAWKYMEEEILGFGKSV
  CDSLGRRHMSTCALCDFCSLKLEQCHSEASLQRQQCDTSHKTPFVSPLLASQSLSIGNQV
  GSPESGRFYGLDLYGGLHMDFWCARLATKGCEDVRVSGWLQTEFLSFQDGDFPTKICDTD
  YIQYPNYCSFKSQQCLMRNRNRKVSRMRCLQNETYSALSPGKSEDVVLRWSQEFSTLTLG
  QFG
• Function: [Acrosin-binding protein, mature form]: Acrosomal protein that maintains proacrosin (pro-ACR) as an enzymatically inactive zymogen in the acrosome. Involved also in the acrosome formation.
• Tissue Specificity: Expression restricted to testis in normal tissue. Expressed in a wide spectrum of cancers, including bladder, breast, liver, lung and colon cancers.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[7]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[9]
Liver cancer	DISDE4BI	Limited	Biomarker	[9]

5 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 Acrosin-binding protein (ACRBP).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acrosin-binding protein (ACRBP).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acrosin-binding protein (ACRBP).	[12]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Acrosin-binding protein (ACRBP).	[14]
Piperazinyl methyl quinazolinone derivative 2	DM913KS	Patented	Piperazinyl methyl quinazolinone derivative 2 increases the expression of Acrosin-binding protein (ACRBP).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Acrosin-binding protein (ACRBP).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acrosin-binding protein (ACRBP).	[15]

References

• [1] Tumor antigen acrosin binding protein normalizes mitotic spindle function to promote cancer cell proliferation.Cancer Res. 2010 Oct 1;70(19):7652-61. doi: 10.1158/0008-5472.CAN-10-0840. Epub 2010 Sep 28.
• [2] Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3282-7. doi: 10.1073/pnas.041625098.
• [3] Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters.Int J Clin Exp Pathol. 2013 Nov 15;6(12):2835-45. eCollection 2013.
• [4] Serum immunoreactivity of cancer/testis antigen OY-TES-1 and its tissues expression in glioma.Oncol Lett. 2017 May;13(5):3080-3086. doi: 10.3892/ol.2017.5799. Epub 2017 Mar 3.
• [5] Down-regulation of cancer/testis antigen OY-TES-1 attenuates malignant behaviors of hepatocellular carcinoma cells in vitro.Int J Clin Exp Pathol. 2015 Jul 1;8(7):7786-97. eCollection 2015.
• [6] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [7] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [8] OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer.Int J Oncol. 2006 Oct;29(4):903-10.
• [9] OY-TES-1 may regulate the malignant behavior of liver cancer via NANOG, CD9, CCND2 and CDCA3: a bioinformatic analysis combine with RNAi and oligonucleotide microarray.Oncol Rep. 2015 Apr;33(4):1965-75. doi: 10.3892/or.2015.3792. Epub 2015 Feb 10.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [15] 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.
• [16] A novel circular RNA confers trastuzumab resistance in human epidermal growth factor receptor 2-positive breast cancer through regulating ferroptosis. Environ Toxicol. 2022 Jul;37(7):1597-1607. doi: 10.1002/tox.23509. Epub 2022 Mar 2.