Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6O7PCT)

• DOT Name: Granzyme K (GZMK)
• Synonyms: EC 3.4.21.-; Fragmentin-3; Granzyme-3; NK-tryptase-2; NK-Tryp-2
• Gene Name: GZMK
• Related Disease:
  Autoimmune disease
  Multiple sclerosis
  Neoplasm
• UniProt ID: GRAK_HUMAN
• PDB ID: 1MZA; 1MZD
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MTKFSSFSLFFLIVGAYMTHVCFNMEIIGGKEVSPHSRPFMASIQYGGHHVCGGVLIDPQ
  WVLTAAHCQYRFTKGQSPTVVLGAHSLSKNEASKQTLEIKKFIPFSRVTSDPQSNDIMLV
  KLQTAAKLNKHVKMLHIRSKTSLRSGTKCKVTGWGATDPDSLRPSDTLREVTVTVLSRKL
  CNSQSYYNGDPFITKDMVCAGDAKGQKDSCKGDSGGPLICKGVFHAIVSGGHECGVATKP
  GIYTLLTKKYQTWIKSNLVPPHTN
• Tissue Specificity: Expressed in lung, spleen, thymus and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Granzyme K (GZMK).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Granzyme K (GZMK).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Granzyme K (GZMK).	[5]
Choline	DM5D9YK	Investigative	Choline affects the expression of Granzyme K (GZMK).	[6]

References

• [1] Unexpected role for granzyme K in CD56bright NK cell-mediated immunoregulation of multiple sclerosis.J Immunol. 2011 Jul 15;187(2):781-90. doi: 10.4049/jimmunol.1100789. Epub 2011 Jun 10.
• [2] Ignition of p53 bomb sensitizes tumor cells to granzyme K-mediated cytolysis.J Immunol. 2009 Feb 15;182(4):2152-9. doi: 10.4049/jimmunol.0802307.
• [3] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [4] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [5] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [6] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.