Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX0OPHO)

• DOT Name: SNF-related serine/threonine-protein kinase (SNRK)
• Synonyms: EC 2.7.11.1; SNF1-related kinase
• Gene Name: SNRK
• Related Disease:
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Gastroesophageal reflux disease
  Cardiomyopathy
• UniProt ID: SNRK_HUMAN
• PDB ID: 5YKS
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MAGFKRGYDGKIAGLYDLDKTLGRGHFAVVKLARHVFTGEKVAVKVIDKTKLDTLATGHL
  FQEVRCMKLVQHPNIVRLYEVIDTQTKLYLILELGDGGDMFDYIMKHEEGLNEDLAKKYF
  AQIVHAISYCHKLHVVHRDLKPENVVFFEKQGLVKLTDFGFSNKFQPGKKLTTSCGSLAY
  SAPEILLGDEYDAPAVDIWSLGVILFMLVCGQPPFQEANDSETLTMIMDCKYTVPSHVSK
  ECKDLITRMLQRDPKRRASLEEIENHPWLQGVDPSPATKYNIPLVSYKNLSEEEHNSIIQ
  RMVLGDIADRDAIVEALETNRYNHITATYFLLAERILREKQEKEIQTRSASPSNIKAQFR
  QSWPTKIDVPQDLEDDLTATPLSHATVPQSPARAADSVLNGHRSKGLCDSAKKDDLPELA
  GPALSTVPPASLKPTASGRKCLFRVEEDEEEDEEDKKPMSLSTQVVLRRKPSVTNRLTSR
  KSAPVLNQIFEEGESDDEFDMDENLPPKLSRLKMNIASPGTVHKRYHRRKSQGRGSSCSS
  SETSDDDSESRRRLDKDSGFTYSWHRRDSSEGPPGSEGDGGGQSKPSNASGGVDKASPSE
  NNAGGGSPSSGSGGNPTNTSGTTRRCAGPSNSMQLASRSAGELVESLKLMSLCLGSQLHG
  STKYIIDPQNGLSFSSVKVQEKSTWKMCISSTGNAGQVPAVGGIKFFSDHMADTTTELER
  IKSKNLKNNVLQLPLCEKTISVNIQRNPKEGLLCASSPASCCHVI
• Function: May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis.
• Tissue Specificity: Expressed in hematopoietic progenitor cells and leukemic cell lines. Weakly expressed in the testis.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Genetic Variation	[3]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[4]

9 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 SNF-related serine/threonine-protein kinase (SNRK).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[10]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SNF-related serine/threonine-protein kinase (SNRK).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SNF-related serine/threonine-protein kinase (SNRK).	[13]

References

• [1] The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis.Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15855-60. doi: 10.1073/pnas.0906993106. Epub 2009 Aug 28.
• [2] Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin-binding protein-dependent reduction of -catenin.FASEB J. 2012 Nov;26(11):4685-95. doi: 10.1096/fj.12-212282. Epub 2012 Aug 8.
• [3] Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.Nat Commun. 2019 Sep 16;10(1):4219. doi: 10.1038/s41467-019-11968-2.
• [4] Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling.Nat Commun. 2017 Jan 24;8:14095. doi: 10.1038/ncomms14095.
• [5] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [12] Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.