Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT239QMC)

• DOT Name: SRSF protein kinase 3 (SRPK3)
• Synonyms: EC 2.7.11.1; Muscle-specific serine kinase 1; MSSK-1; Serine/arginine-rich protein-specific kinase 3; SR-protein-specific kinase 3; Serine/threonine-protein kinase 23
• Gene Name: SRPK3
• Related Disease:
  Nemaline myopathy
  Intellectual disability
• UniProt ID: SRPK3_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MSASTGGGGDSGGSGGSSSSSQASCGPESSGSELALATPVPQMLQGLLGSDDEEQEDPKD
  YCKGGYHPVKIGDVFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAGHYTETA
  VDEIKLLKCVRDSDPSDPKRETIVQLIDDFRISGVNGVHVCMVLEVLGHQLLKWIIKSNY
  QGLPVPCVKSIVRQVLHGLDYLHTKCKIIHTDIKPENILLCVGDAYIRRLAAEATEWQQA
  GAPPPSRSIVSTAPQEVLQTGKLSKNKRKKMRRKRKQQKRLLEERLRDLQRLEAMEAATQ
  AEDSGLRLDGGSGSTSSSGCHPGGARAGPSPASSSPAPGGGRSLSAGSQTSGFSGSLFSP
  ASCSILSGSSNQRETGGLLSPSTPFGASNLLVNPLEPQNADKIKIKIADLGNACWVHKHF
  TEDIQTRQYRAVEVLIGAEYGPPADIWSTACMAFELATGDYLFEPHSGEDYSRDEDHIAH
  IVELLGDIPPAFALSGRYSREFFNRRGELRHIHNLKHWGLYEVLMEKYEWPLEQATQFSA
  FLLPMMEYIPEKRASAADCLQHPWLNP
• Function: Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. Phosphorylates the SR splicing factor SRSF1 and the lamin-B receptor (LBR) in vitro. Required for normal muscle development.
• Tissue Specificity: Exclusively expressed in skeletal and heart muscle.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nemaline myopathy	DIS5IYLY	Definitive	Biomarker	[1]
Intellectual disability	DISMBNXP	Limited	X-linked	[2]

2 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 SRSF protein kinase 3 (SRPK3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SRSF protein kinase 3 (SRPK3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SRSF protein kinase 3 (SRPK3).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SRSF protein kinase 3 (SRPK3).	[6]

References

• [1] Next generation sequencing reveals ryanodine receptor 1 mutations in a Chinese central core disease cohort.Muscle Nerve. 2016 Sep;54(3):432-8. doi: 10.1002/mus.25050. Epub 2016 May 25.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] 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.