Details of Drug Off-Target (DOT)

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

DOT Name	Serine/threonine-protein kinase 24 (STK24)
Synonyms	EC 2.7.11.1; Mammalian STE20-like protein kinase 3; MST-3; STE20-like kinase MST3
Gene Name	STK24
Related Disease	Cryptosporidium infection ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Colitis ( ) Colorectal carcinoma ( ) Essential hypertension ( ) High blood pressure ( ) Lung adenocarcinoma ( ) Major depressive disorder ( ) Malaria ( ) Male infertility ( ) Neoplasm ( ) Osteoporosis ( ) Pancreatic cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Pseudohypoaldosteronism type 2 ( ) Pseudohypoaldosteronism type 2D ( ) Schizophrenia ( ) Keratoconus ( ) Advanced cancer ( ) Gastric cancer ( ) Hyperglycemia ( ) Hyperinsulinemia ( ) Inflammation ( ) Nervous system inflammation ( ) Non-alcoholic steatohepatitis ( ) Pseudopseudohypoparathyroidism ( ) Stomach cancer ( )
UniProt ID	STK24_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3A7F ; 3A7G ; 3A7H ; 3A7I ; 3A7J ; 3CKW ; 3CKX ; 3ZHP ; 4O27 ; 4QML ; 4QMM ; 4QMN ; 4QMO ; 4QMP ; 4QMQ ; 4QMS ; 4QMT ; 4QMU ; 4QMV ; 4QMW ; 4QMX ; 4QMY ; 4QMZ ; 4QNA ; 4QO9 ; 4U8Z ; 4W8D ; 4W8E ; 7B30 ; 7B31 ; 7B32 ; 7B33 ; 7B34 ; 7B35 ; 8BZI ; 8BZJ ; 8QLQ ; 8QLR ; 8QLS ; 8QLT
EC Number	2.7.11.1
Pfam ID	PF20929 ; PF00069
Sequence	MDSRAQLWGLALNKRRATLPHPGGSTNLKADPEELFTKLEKIGKGSFGEVFKGIDNRTQK VVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGSAL DLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQ LTDTQIKRNTFVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVL FLIPKNNPPTLEGNYSKPLKEFVEACLNKEPSFRPTAKELLKHKFILRNAKKTSYLTELI DRYKRWKAEQSHDDSSSEDSDAETDGQASGGSDSGDWIFTIREKDPKNLENGALQPSDLD RNKMKDIPKRPFSQCLSTIISPLFAELKEKSQACGGNLGSIEELRGAIYLAEEACPGISD TMVAQLVQRLQRYSLSGGGTSSH
Function	Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation. Regulates also cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.
Tissue Specificity	Isoform A is ubiquitous. Isoform B is expressed in brain with high expression in hippocampus and cerebral cortex.
Reactome Pathway	Apoptotic execution phase (R-HSA-75153 ) Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cryptosporidium infection	DISLBTU2	Definitive	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Colitis	DISAF7DD	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Essential hypertension	DIS7WI98	Strong	Biomarker	[6]
High blood pressure	DISY2OHH	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[8]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[9]
Malaria	DISQ9Y50	Strong	Biomarker	[10]
Male infertility	DISY3YZZ	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[13]
Pancreatic cancer	DISJC981	Strong	Biomarker	[14]
Prostate cancer	DISF190Y	Strong	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[15]
Pseudohypoaldosteronism type 2	DISFTCHO	Strong	Altered Expression	[16]
Pseudohypoaldosteronism type 2D	DIS2AO4N	Strong	Genetic Variation	[17]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[18]
Keratoconus	DISOONXH	moderate	Biomarker	[19]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[20]
Gastric cancer	DISXGOUK	Limited	Biomarker	[21]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[22]
Hyperinsulinemia	DISIDWT6	Limited	Biomarker	[22]
Inflammation	DISJUQ5T	Limited	Biomarker	[23]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[23]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[24]
Pseudopseudohypoparathyroidism	DISRRO5I	Limited	Biomarker	[25]
Stomach cancer	DISKIJSX	Limited	Biomarker	[21]
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⏷ Show the Full List of 30 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine-protein kinase 24 (STK24).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase 24 (STK24).	[27]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Serine/threonine-protein kinase 24 (STK24).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/threonine-protein kinase 24 (STK24).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serine/threonine-protein kinase 24 (STK24).	[30]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine/threonine-protein kinase 24 (STK24).	[31]
Selenium	DM25CGV	Approved	Selenium increases the expression of Serine/threonine-protein kinase 24 (STK24).	[32]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Serine/threonine-protein kinase 24 (STK24).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine/threonine-protein kinase 24 (STK24).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase 24 (STK24).	[36]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of Serine/threonine-protein kinase 24 (STK24).	[38]
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⏷ Show the Full List of 11 Drug(s)

2 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 affects the methylation of Serine/threonine-protein kinase 24 (STK24).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein kinase 24 (STK24).	[37]
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References

1	Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe.FEMS Yeast Res. 2006 Jun;6(4):614-9. doi: 10.1111/j.1567-1364.2006.00081.x.
2	Mixed lineage kinase 3 promotes breast tumorigenesis via phosphorylation and activation of p21-activated kinase 1.Oncogene. 2019 May;38(19):3569-3584. doi: 10.1038/s41388-019-0690-0. Epub 2019 Jan 21.
3	MST3 promotes proliferation and tumorigenicity through the VAV2/Rac1 signal axis in breast cancer.Oncotarget. 2016 Mar 22;7(12):14586-604. doi: 10.18632/oncotarget.7542.
4	Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.J Immunol. 2011 Aug 1;187(3):1496-505. doi: 10.4049/jimmunol.1002910. Epub 2011 Jun 24.
5	microRNA-222 promotes colorectal cancer cell migration and invasion by targeting MST3.FEBS Open Bio. 2019 May;9(5):901-913. doi: 10.1002/2211-5463.12623. Epub 2019 Apr 2.
6	Cotransporters, WNKs and hypertension: an update.Curr Opin Nephrol Hypertens. 2008 Mar;17(2):186-92. doi: 10.1097/MNH.0b013e3282f5244e.
7	MST3 is involved in ENaC-mediated hypertension.Am J Physiol Renal Physiol. 2019 Jul 1;317(7):F30-F42. doi: 10.1152/ajprenal.00455.2018. Epub 2019 Apr 10.
8	STK24 expression is modulated by DNA copy number/methylation in lung adenocarcinoma and predicts poor survival.Future Oncol. 2018 Sep;14(22):2253-2263. doi: 10.2217/fon-2018-0126. Epub 2018 Mar 20.
9	Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
10	Negligible Impact of Mass Screening and Treatment on Mesoendemic Malaria Transmission at West Timor in Eastern Indonesia: A Cluster-Randomized Trial.Clin Infect Dis. 2018 Oct 15;67(9):1364-1372. doi: 10.1093/cid/ciy231.
11	Proteomic Profiling Analysis of Male Infertility in Spodoptera Litura Larvae Challenged with Azadirachtin and its Potential-Regulated Pathways in the Following Stages.Proteomics. 2018 Oct;18(19):e1800192. doi: 10.1002/pmic.201800192. Epub 2018 Sep 2.
12	Tumor suppressor C-RASSF proteins.Cell Mol Life Sci. 2018 May;75(10):1773-1787. doi: 10.1007/s00018-018-2756-5. Epub 2018 Jan 20.
13	Effect of Plastrum Testudinis Extracts on the Proliferation and Osteogenic Differentiation of rBMSCs by Regulating p38 MAPK-Related Genes.Evid Based Complement Alternat Med. 2019 Mar 7;2019:6815620. doi: 10.1155/2019/6815620. eCollection 2019.
14	The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1.J Biol Chem. 2014 Feb 14;289(7):4009-17. doi: 10.1074/jbc.M113.520106. Epub 2013 Dec 20.
15	The Ste20 kinase MST4 plays a role in prostate cancer progression.Cancer Res. 2003 Jun 15;63(12):3356-63.
16	Regulation of with-no-lysine kinase signaling by Kelch-like proteins.Biol Cell. 2014 Feb;106(2):45-56. doi: 10.1111/boc.201300069. Epub 2014 Jan 10.
17	Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1 mutations: evidence for differential roles of WNK1 and WNK4.Sci Rep. 2018 Feb 19;8(1):3249. doi: 10.1038/s41598-018-21405-x.
18	Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
19	Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant Identification.Ophthalmic Genet. 2016;37(1):37-43. doi: 10.3109/13816810.2014.926375. Epub 2014 Jun 18.
20	TNIK serves as a novel biomarker associated with poor prognosis in patients with pancreatic cancer.Tumour Biol. 2016 Jan;37(1):1035-40. doi: 10.1007/s13277-015-3881-5. Epub 2015 Aug 14.
21	The oncogenic role of MST3 in human gastric cancer.Am J Cancer Res. 2018 Oct 1;8(10):2130-2139. eCollection 2018.
22	The MST3/STK24 kinase mediates impaired fasting blood glucose after a high-fat diet.Diabetologia. 2017 Dec;60(12):2453-2462. doi: 10.1007/s00125-017-4433-x. Epub 2017 Sep 27.
23	Protein Kinase Serine/Threonine Kinase 24 Positively Regulates Interleukin 17-Induced Inflammation by Promoting IKK Complex Activation.Front Immunol. 2018 Apr 30;9:921. doi: 10.3389/fimmu.2018.00921. eCollection 2018.
24	Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans.FASEB J. 2019 Sep;33(9):9974-9989. doi: 10.1096/fj.201900356RR. Epub 2019 Jun 7.
25	STK25 is a candidate gene for pseudopseudohypoparathyroidism.Genomics. 2001 Sep;77(1-2):2-4. doi: 10.1006/geno.2001.6605.
26	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.
27	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
28	Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
29	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.
30	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
31	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.
32	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
33	Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
34	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35	Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
36	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
37	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.
38	Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.