Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLRN4L1)

• DOT Name: CYFIP-related Rac1 interactor B (CYRIB)
• Synonyms: L1
• Gene Name: CYRIB
• Related Disease:
  Advanced cancer
  Aerodigestive tract cancer
  Bacterial infection
  Colorectal carcinoma
  Gastric cancer
  Neoplasm
  Non-insulin dependent diabetes
  Rheumatoid arthritis
  Salmonella infection
  Stomach cancer
  Tuberculosis
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Post-traumatic stress disorder
• UniProt ID: CYRIB_HUMAN
• PDB ID: 7AJK
• Pfam ID: PF07159
• Sequence:
  MGNLLKVLTCTDLEQGPNFFLDFENAQPTESEKEIYNQVNVVLKDAEGILEDLQSYRGAG
  HEIREAIQHPADEKLQEKAWGAVVPLVGKLKKFYEFSQRLEAALRGLLGALTSTPYSPTQ
  HLEREQALAKQFAEILHFTLRFDELKMTNPAIQNDFSYYRRTLSRMRINNVPAEGENEVN
  NELANRMSLFYAEATPMLKTLSDATTKFVSENKNLPIENTTDCLSTMASVCRVMLETPEY
  RSRFTNEETVSFCLRVMVGVIILYDHVHPVGAFAKTSKIDMKGCIKVLKDQPPNSVEGLL
  NALRYTTKHLNDETTSKQIKSMLQ
• Function: Negatively regulates RAC1 signaling and RAC1-driven cytoskeletal remodeling. Regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions. Limits Rac1 mediated activation of the Scar/WAVE complex, focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. Protects against Salmonella bacterial infection. Attenuates processes such as macropinocytosis, phagocytosis and cell migration and restrict sopE-mediated bacterial entry. Restricts also infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes. Involved in the regulation of mitochondrial dynamics and oxidative stress.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

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	Genetic Variation	[1]
Aerodigestive tract cancer	DIS3AOQ7	Strong	Biomarker	[2]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]
Salmonella infection	DISTJ434	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[4]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[3]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[6]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[7]

2 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 CYFIP-related Rac1 interactor B (CYRIB).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CYFIP-related Rac1 interactor B (CYRIB).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CYFIP-related Rac1 interactor B (CYRIB).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CYFIP-related Rac1 interactor B (CYRIB).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CYFIP-related Rac1 interactor B (CYRIB).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CYFIP-related Rac1 interactor B (CYRIB).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CYFIP-related Rac1 interactor B (CYRIB).	[10]

References

• [1] Hepatic transcriptome and proteome analyses provide new insights into the regulator mechanism of dietary avicularin in diabetic mice.Food Res Int. 2019 Nov;125:108570. doi: 10.1016/j.foodres.2019.108570. Epub 2019 Jul 19.
• [2] ZFR promotes cell proliferation and tumor development in colorectal and liver cancers.Biochem Biophys Res Commun. 2019 Jun 11;513(4):1027-1034. doi: 10.1016/j.bbrc.2019.04.103. Epub 2019 Apr 19.
• [3] CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection.Nat Microbiol. 2019 Sep;4(9):1516-1531. doi: 10.1038/s41564-019-0484-8. Epub 2019 Jul 8.
• [4] Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis.Gastric Cancer. 2019 Jul;22(4):731-741. doi: 10.1007/s10120-018-00915-7. Epub 2019 Jan 2.
• [5] Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset.J Adv Res. 2019 Jan 18;18:113-126. doi: 10.1016/j.jare.2019.01.006. eCollection 2019 Jul.
• [6] FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis.Oncogene. 2018 Feb 8;37(6):697-709. doi: 10.1038/onc.2017.358. Epub 2017 Oct 23.
• [7] Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder.Biol Psychiatry. 2013 Nov 1;74(9):656-63. doi: 10.1016/j.biopsych.2013.04.013. Epub 2013 May 28.
• [8] 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.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] 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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.