Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT98KLEL)

• DOT Name: Serine/threonine-protein kinase 33 (STK33)
• Synonyms: EC 2.7.11.1
• Gene Name: STK33
• UniProt ID: STK33_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MADSGLDKKSTKCPDCSSASQKDVLCVCSSKTRVPPVLVVEMSQTSSIGSAESLISLERK
  KEKNINRDITSRKDLPSRTSNVERKASQQQWGRGNFTEGKVPHIRIENGAAIEEIYTFGR
  ILGKGSFGIVIEATDKETETKWAIKKVNKEKAGSSAVKLLEREVNILKSVKHEHIIHLEQ
  VFETPKKMYLVMELCEDGELKEILDRKGHFSENETRWIIQSLASAIAYLHNNDIVHRDLK
  LENIMVKSSLIDDNNEINLNIKVTDFGLAVKKQSRSEAMLQATCGTPIYMAPEVISAHDY
  SQQCDIWSIGVVMYMLLRGEPPFLASSEEKLFELIRKGELHFENAVWNSISDCAKSVLKQ
  LMKVDPAHRITAKELLDNQWLTGNKLSSVRPTNVLEMMKEWKNNPESVEENTTEEKNKPS
  TEEKLKSYQPWGNVPDANYTSDEEEEKQSTAYEKQFPATSKDNFDMCSSSFTSSKLLPAE
  IKGEMEKTPVTPSQGTATKYPAKSGALSRTKKKL
• Function: Serine/threonine protein kinase which phosphorylates VIME. May play a specific role in the dynamic behavior of the intermediate filament cytoskeleton by phosphorylation of VIME. Not essential for the survival of KRAS-dependent AML cell lines.
• Tissue Specificity: Highly expressed in testis, fetal lung and heart, followed by pituitary gland, kidney, interventricular septum, pancreas, heart, trachea, thyroid gland and uterus. Weak hybridization signals were observed in the following tissues: amygdala, aorta, esophagus, colon ascending, colon transverse, skeletal muscle, spleen, peripheral blood leukocyte, lymph node, bone marrow, placenta, prostate, liver, salivary gland, mammary gland, some tumor cell lines, fetal brain, fetal liver, fetal spleen and fetal thymus. No signal at all was detectable in RNA from tissues of the nervous system.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serine/threonine-protein kinase 33 (STK33).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein kinase 33 (STK33).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine/threonine-protein kinase 33 (STK33).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein kinase 33 (STK33).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Serine/threonine-protein kinase 33 (STK33).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase 33 (STK33).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase 33 (STK33).	[7]

References

• [1] 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.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] 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.
• [7] 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.