Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQI8R56)

• DOT Name: SCY1-like protein 2 (SCYL2)
• Synonyms: Coated vesicle-associated kinase of 104 kDa
• Gene Name: SCYL2
• Related Disease: Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum
• UniProt ID: SCYL2_HUMAN
• Pfam ID: PF00069
• Sequence:
  MESMLNKLKSTVTKVTADVTSAVMGNPVTREFDVGRHIASGGNGLAWKIFNGTKKSTKQE
  VAVFVFDKKLIDKYQKFEKDQIIDSLKRGVQQLTRLRHPRLLTVQHPLEESRDCLAFCTE
  PVFASLANVLGNWENLPSPISPDIKDYKLYDVETKYGLLQVSEGLSFLHSSVKMVHGNIT
  PENIILNKSGAWKIMGFDFCVSSTNPSEQEPKFPCKEWDPNLPSLCLPNPEYLAPEYILS
  VSCETASDMYSLGTVMYAVFNKGKPIFEVNKQDIYKSFSRQLDQLSRLGSSSLTNIPEEV
  REHVKLLLNVTPTVRPDADQMTKIPFFDDVGAVTLQYFDTLFQRDNLQKSQFFKGLPKVL
  PKLPKRVIVQRILPCLTSEFVNPDMVPFVLPNVLLIAEECTKEEYVKLILPELGPVFKQQ
  EPIQILLIFLQKMDLLLTKTPPDEIKNSVLPMVYRALEAPSIQIQELCLNIIPTFANLID
  YPSMKNALIPRIKNACLQTSSLAVRVNSLVCLGKILEYLDKWFVLDDILPFLQQIPSKEP
  AVLMGILGIYKCTFTHKKLGITKEQLAGKVLPHLIPLSIENNLNLNQFNSFISVIKEMLN
  RLESEHKTKLEQLHIMQEQQKSLDIGNQMNVSEEMKVTNIGNQQIDKVFNNIGADLLTGS
  ESENKEDGLQNKHKRASLTLEEKQKLAKEQEQAQKLKSQQPLKPQVHTPVATVKQTKDLT
  DTLMDNMSSLTSLSVSTPKSSASSTFTSVPSMGIGMMFSTPTDNTKRNLTNGLNANMGFQ
  TSGFNMPVNTNQNFYSSPSTVGVTKMTLGTPPTLPNFNALSVPPAGAKQTQQRPTDMSAL
  NNLFGPQKPKVSMNQLSQQKPNQWLNQFVPPQGSPTMGSSVMGTQMNVIGQSAFGMQGNP
  FFNPQNFAQPPTTMTNSSSASNDLKDLFG
• Function: Component of the AP2-containing clathrin coat that may regulate clathrin-dependent trafficking at plasma membrane, TGN and endosomal system (Probable). A possible serine/threonine-protein kinase toward the beta2-subunit of the plasma membrane adapter complex AP2 and other proteins in presence of poly-L-lysine has not been confirmed. By regulating the expression of excitatory receptors at synapses, plays an essential role in neuronal function and signaling and in brain development.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	DISYA1OJ	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of SCY1-like protein 2 (SCYL2).	[2]

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 SCY1-like protein 2 (SCYL2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SCY1-like protein 2 (SCYL2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SCY1-like protein 2 (SCYL2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SCY1-like protein 2 (SCYL2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of SCY1-like protein 2 (SCYL2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SCY1-like protein 2 (SCYL2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SCY1-like protein 2 (SCYL2).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of SCY1-like protein 2 (SCYL2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SCY1-like protein 2 (SCYL2).	[11]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of SCY1-like protein 2 (SCYL2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SCY1-like protein 2 (SCYL2).	[13]

References

• [1] SCYL2 Protects CA3 Pyramidal Neurons from Excitotoxicity during Functional Maturation of the Mouse Hippocampus. J Neurosci. 2015 Jul 22;35(29):10510-22. doi: 10.1523/JNEUROSCI.2056-14.2015.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.