Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8O184)

• DOT Name: Coagulation factor XIII A chain (F13A1)
• Synonyms: Coagulation factor XIIIa; EC 2.3.2.13; Protein-glutamine gamma-glutamyltransferase A chain; Transglutaminase A chain
• Gene Name: F13A1
• Related Disease:
  Factor XIII, A subunit, deficiency of
  Congenital factor XIII deficiency
• UniProt ID: F13A_HUMAN
• PDB ID: 1EVU; 1EX0; 1F13; 1FIE; 1GGT; 1GGU; 1GGY; 1QRK; 4KTY; 5MHL; 5MHM; 5MHN; 5MHO
• EC Number: 2.3.2.13
• Pfam ID: PF00927 ; PF01841 ; PF00868
• Sequence:
  MSETSRTAFGGRRAVPPNNSNAAEDDLPTVELQGVVPRGVNLQEFLNVTSVHLFKERWDT
  NKVDHHTDKYENNKLIVRRGQSFYVQIDFSRPYDPRRDLFRVEYVIGRYPQENKGTYIPV
  PIVSELQSGKWGAKIVMREDRSVRLSIQSSPKCIVGKFRMYVAVWTPYGVLRTSRNPETD
  TYILFNPWCEDDAVYLDNEKEREEYVLNDIGVIFYGEVNDIKTRSWSYGQFEDGILDTCL
  YVMDRAQMDLSGRGNPIKVSRVGSAMVNAKDDEGVLVGSWDNIYAYGVPPSAWTGSVDIL
  LEYRSSENPVRYGQCWVFAGVFNTFLRCLGIPARIVTNYFSAHDNDANLQMDIFLEEDGN
  VNSKLTKDSVWNYHCWNEAWMTRPDLPVGFGGWQAVDSTPQENSDGMYRCGPASVQAIKH
  GHVCFQFDAPFVFAEVNSDLIYITAKKDGTHVVENVDATHIGKLIVTKQIGGDGMMDITD
  TYKFQEGQEEERLALETALMYGAKKPLNTEGVMKSRSNVDMDFEVENAVLGKDFKLSITF
  RNNSHNRYTITAYLSANITFYTGVPKAEFKKETFDVTLEPLSFKKEAVLIQAGEYMGQLL
  EQASLHFFVTARINETRDVLAKQKSTVLTIPEIIIKVRGTQVVGSDMTVTVEFTNPLKET
  LRNVWVHLDGPGVTRPMKKMFREIRPNSTVQWEEVCRPWVSGHRKLIASMSSDSLRHVYG
  ELDVQIQRRPSM
• Function: Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Platelet degranulation (R-HSA-114608)
• BioCyc Pathway: MetaCyc:ENSG00000124491-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, A subunit, deficiency of	DISKEGBP	Definitive	Autosomal recessive	[1]
Congenital factor XIII deficiency	DISZIQLL	Supportive	Autosomal recessive	[2]

18 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 Coagulation factor XIII A chain (F13A1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coagulation factor XIII A chain (F13A1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coagulation factor XIII A chain (F13A1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Coagulation factor XIII A chain (F13A1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coagulation factor XIII A chain (F13A1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Coagulation factor XIII A chain (F13A1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Coagulation factor XIII A chain (F13A1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coagulation factor XIII A chain (F13A1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Coagulation factor XIII A chain (F13A1).	[11]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Coagulation factor XIII A chain (F13A1).	[12]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Coagulation factor XIII A chain (F13A1).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Coagulation factor XIII A chain (F13A1).	[10]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Coagulation factor XIII A chain (F13A1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coagulation factor XIII A chain (F13A1).	[16]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Coagulation factor XIII A chain (F13A1).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Coagulation factor XIII A chain (F13A1).	[17]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Coagulation factor XIII A chain (F13A1).	[18]
Iodoacetamide	DMM4XVL	Investigative	Iodoacetamide decreases the activity of Coagulation factor XIII A chain (F13A1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Coagulation factor XIII A chain (F13A1).	[15]

References

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• [2] Novel aspects of factor XIII deficiency. Curr Opin Hematol. 2011 Sep;18(5):366-72. doi: 10.1097/MOH.0b013e3283497e3e.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [7] 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.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] 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.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [13] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [14] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [18] In vitro effects of lead on gene expression in neural stem cells and associations between up-regulated genes and cognitive scores in children. Environ Health Perspect. 2017 Apr;125(4):721-729.
• [19] Molecular mechanisms underlying the proangiogenic effect of factor XIII. Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):526-32. doi: 10.1161/01.ATV.0000154137.21230.80. Epub 2004 Dec 23.