Details of Drug Off-Target (DOT)

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

• DOT Name: Coagulation factor XIII B chain (F13B)
• Synonyms: Fibrin-stabilizing factor B subunit; Protein-glutamine gamma-glutamyltransferase B chain; Transglutaminase B chain
• Gene Name: F13B
• Related Disease:
  Factor XIII, b subunit, deficiency of
  Congenital factor XIII deficiency
• UniProt ID: F13B_HUMAN
• Pfam ID: PF00084
• Sequence:
  MRLKNLTFIIILIISGELYAEEKPCGFPHVENGRIAQYYYTFKSFYFPMSIDKKLSFFCL
  AGYTTESGRQEEQTTCTTEGWSPEPRCFKKCTKPDLSNGYISDVKLLYKIQENMRYGCAS
  GYKTTGGKDEEVVQCLSDGWSSQPTCRKEHETCLAPELYNGNYSTTQKTFKVKDKVQYEC
  ATGYYTAGGKKTEEVECLTYGWSLTPKCTKLKCSSLRLIENGYFHPVKQTYEEGDVVQFF
  CHENYYLSGSDLIQCYNFGWYPESPVCEGRRNRCPPPPLPINSKIQTHSTTYRHGEIVHI
  ECELNFEIHGSAEIRCEDGKWTEPPKCIEGQEKVACEEPPFIENGAANLHSKIYYNGDKV
  TYACKSGYLLHGSNEITCNRGKWTLPPECVENNENCKHPPVVMNGAVADGILASYATGSS
  VEYRCNEYYLLRGSKISRCEQGKWSSPPVCLEPCTVNVDYMNRNNIEMKWKYEGKVLHGD
  LIDFVCKQGYDLSPLTPLSELSVQCNRGEVKYPLCTRKESKGMCTSPPLIKHGVIISSTV
  DTYENGSSVEYRCFDHHFLEGSREAYCLDGMWTTPPLCLEPCTLSFTEMEKNNLLLKWDF
  DNRPHILHGEYIEFICRGDTYPAELYITGSILRMQCDRGQLKYPRCIPRQSTLSYQEPLR
  T
• Function: The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway: Common Pathway of Fibrin Clot Formation (R-HSA-140875)
• BioCyc Pathway: MetaCyc:ENSG00000143278-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Factor XIII, b subunit, deficiency of	DISCXR1Y	Definitive	Autosomal recessive	[1]
Congenital factor XIII deficiency	DISZIQLL	Supportive	Autosomal recessive	[2]

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 Coagulation factor XIII B chain (F13B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coagulation factor XIII B chain (F13B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coagulation factor XIII B chain (F13B).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coagulation factor XIII B chain (F13B).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Coagulation factor XIII B chain (F13B).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Coagulation factor XIII B chain (F13B).	[7]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Coagulation factor XIII B chain (F13B).	[8]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Coagulation factor XIII B chain (F13B).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coagulation factor XIII B chain (F13B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Coagulation factor XIII B chain (F13B).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Coagulation factor XIII B chain (F13B).	[13]

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 Coagulation factor XIII B chain (F13B).	[12]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Novel aspects of factor XIII deficiency. Curr Opin Hematol. 2011 Sep;18(5):366-72. doi: 10.1097/MOH.0b013e3283497e3e.
• [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] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [9] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [12] 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.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.