Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI4AFZL)

• DOT Name: Ankyrin repeat and SOCS box protein 4 (ASB4)
• Synonyms: ASB-4
• Gene Name: ASB4
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Neoplasm
  Pre-eclampsia
• UniProt ID: ASB4_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF13637 ; PF07525
• Sequence:
  MDGTTAPVTKSGAAKLVKRNFLEALKSNDFGKLKAILIQRQIDVDTVFEVEDENMVLASY
  KQGYWLPSYKLKSSWATGLHLSVLFGHVECLLVLLDHNATINCRPNGKTPLHVACEMANV
  DCVKILCDRGAKLNCYSLSGHTALHFCTTPSSILCAKQLVWRGANVNMKTNNQDEETPLH
  TAAHFGLSELVAFYVEHGAIVDSVNAHMETPLAIAAYWALRFKEQEYSTEHHLVCRMLLD
  YKAEVNARDDDFKSPLHKAAWNCDHVLMHMMLEAGAEANLMDINGCAAIQYVLKVTSVRP
  AAQPEICYQLLLNHGAARIYPPQFHKVIQACHSCPKAIEVVVNAYEHIRWNTKWRRAIPD
  DDLEKYWDFYHSLFTVCCNSPRTLMHLSRCAIRRTLHNRCHRAIPLLSLPLSLKKYLLLE
  PEGIIY
• Function: Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes differentiation and maturation of the vascular lineage by an oxygen-dependent mechanism.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pre-eclampsia	DISY7Q29	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[8]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin repeat and SOCS box protein 4 (ASB4).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Ankyrin repeat and SOCS box protein 4 (ASB4).	[5]

References

• [1] The Antigen ASB4 on Cancer Stem Cells Serves as a Target for CTL Immunotherapy of Colorectal Cancer.Cancer Immunol Res. 2018 Mar;6(3):358-369. doi: 10.1158/2326-6066.CIR-17-0518. Epub 2018 Jan 25.
• [2] Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia.Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13450-13455. doi: 10.1073/pnas.1614947113. Epub 2016 Nov 7.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.