Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7V07NI)

• DOT Name: Fetuin-B (FETUB)
• Synonyms: 16G2; Fetuin-like protein IRL685; Gugu
• Gene Name: FETUB
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Chronic kidney disease
  Fatty liver disease
  Hepatocellular carcinoma
  Intrahepatic cholestasis of pregnancy
  Metabolic disorder
  Neoplasm
  Non-insulin dependent diabetes
  Skin neoplasm
  Squamous cell carcinoma
  Type-1/2 diabetes
  Vitamin D deficiency
  Acute myelogenous leukaemia
  Acute coronary syndrome
  Coronary atherosclerosis
  Coronary heart disease
  Obesity
• UniProt ID: FETUB_HUMAN
• PDB ID: 6SAZ; 7UAI
• Pfam ID: PF00031
• Sequence:
  MGLLLPLALCILVLCCGAMSPPQLALNPSALLSRGCNDSDVLAVAGFALRDINKDRKDGY
  VLRLNRVNDAQEYRRGGLGSLFYLTLDVLETDCHVLRKKAWQDCGMRIFFESVYGQCKAI
  FYMNNPSRVLYLAAYNCTLRPVSKKKIYMTCPDCPSSIPTDSSNHQVLEAATESLAKYNN
  ENTSKQYSLFKVTRASSQWVVGPSYFVEYLIKESPCTKSQASSCSLQSSDSVPVGLCKGS
  LTRTHWEKFVSVTCDFFESQAPATGSENSAVNQKPTNLPKVEESQQKNTPPTDSPSKAGP
  RGSVQYLPDLDDKNSQEKGPQEAFPVHLDLTTNPQGETLDISFLFLEPMEEKLVVLPFPK
  EKARTAECPGPAQNASPLVLPP
• Function: Protease inhibitor required for egg fertilization. Required to prevent premature zona pellucida hardening before fertilization, probably by inhibiting the protease activity of ASTL, a protease that mediates the cleavage of ZP2 and triggers zona pellucida hardening.
• Tissue Specificity: Liver and testis.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[4]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Intrahepatic cholestasis of pregnancy	DISMHS5F	Strong	Biomarker	[7]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[10]
Skin neoplasm	DIS16DDV	Strong	Genetic Variation	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[11]
Vitamin D deficiency	DISAWKYI	Strong	Biomarker	[8]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[12]
Acute coronary syndrome	DIS7DYEW	Disputed	Biomarker	[13]
Coronary atherosclerosis	DISKNDYU	Disputed	Biomarker	[13]
Coronary heart disease	DIS5OIP1	Disputed	Biomarker	[13]
Obesity	DIS47Y1K	Limited	Biomarker	[14]

11 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 Fetuin-B (FETUB).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fetuin-B (FETUB).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fetuin-B (FETUB).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fetuin-B (FETUB).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fetuin-B (FETUB).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Fetuin-B (FETUB).	[19]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Fetuin-B (FETUB).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fetuin-B (FETUB).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fetuin-B (FETUB).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fetuin-B (FETUB).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Fetuin-B (FETUB).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fetuin-B (FETUB).	[22]

References

• [1] The serum protein fetuin-B is involved in the development of acute myocardial infarction.Clin Sci (Lond). 2015 Jul;129(1):27-38. doi: 10.1042/CS20140462.
• [2] Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases.Sci Rep. 2019 Jan 24;9(1):546. doi: 10.1038/s41598-018-37024-5.
• [3] Association of Fetuin-B with Subclinical Atherosclerosis in Obese Chinese Adults.J Atheroscler Thromb. 2020 May 1;27(5):418-428. doi: 10.5551/jat.49619. Epub 2019 Sep 13.
• [4] Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study.Ann Nutr Metab. 2019;74(4):287-295. doi: 10.1159/000499843. Epub 2019 Apr 9.
• [5] Fetuin B aggravates liver X receptor-mediated hepatic steatosis through AMPK in HepG2 cells and mice.Am J Transl Res. 2019 Mar 15;11(3):1498-1509. eCollection 2019.
• [6] The liver of woodchucks chronically infected with the woodchuck hepatitis virus contains foci of virus core antigen-negative hepatocytes with both altered and normal morphology.Virology. 2007 Mar 15;359(2):283-94. doi: 10.1016/j.virol.2006.09.034. Epub 2006 Oct 31.
• [7] Increased levels of the novel hepatokine fetuin B in patients with intrahepatic cholestasis of pregnancy.J Matern Fetal Neonatal Med. 2019 May;32(10):1620-1625. doi: 10.1080/14767058.2017.1413546. Epub 2017 Dec 12.
• [8] Fetuin B links vitamin D deficiency and pediatric obesity: Direct negative regulation by vitamin D.J Steroid Biochem Mol Biol. 2018 Sep;182:37-49. doi: 10.1016/j.jsbmb.2018.04.009. Epub 2018 Apr 21.
• [9] Identification of Fetuin-B as a member of a cystatin-like gene family on mouse chromosome 16 with tumor suppressor activity.Genome. 2004 Oct;47(5):931-46. doi: 10.1139/g04-043.
• [10] Effects of aerobic versus resistance training on serum fetuin-A, fetuin-B, and fibroblast growth factor-21 levels in male diabetic patients.Physiol Int. 2019 Mar 1;106(1):70-80. doi: 10.1556/2060.106.2019.01. Epub 2019 Mar 19.
• [11] Fetuin-B links nonalcoholic fatty liver disease to type 2 diabetes via inducing insulin resistance: Association and path analyses.Cytokine. 2018 Aug;108:145-150. doi: 10.1016/j.cyto.2018.03.023. Epub 2018 Mar 30.
• [12] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [13] Increased serum levels of fetuin B in patients with coronary artery disease.Endocrine. 2017 Oct;58(1):97-105. doi: 10.1007/s12020-017-1387-1. Epub 2017 Aug 19.
• [14] Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial.J Clin Endocrinol Metab. 2019 Jul 1;104(7):2719-2727. doi: 10.1210/jc.2018-02378.
• [15] 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.
• [16] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [17] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [20] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.