Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ9I0QU)

• DOT Name: Caskin-1 (CASKIN1)
• Synonyms: CASK-interacting protein 1
• Gene Name: CASKIN1
• Related Disease:
  Anxiety
  Anxiety disorder
• UniProt ID: CSKI1_HUMAN
• PDB ID: 3SEI; 3SEN; 7ATY
• Pfam ID: PF12796 ; PF13637 ; PF16907 ; PF16632 ; PF16600 ; PF00536 ; PF07653
• Sequence:
  MGKEQELVQAVKAEDVGTAQRLLQRPRPGKAKLLGSTKKINVNFQDPDGFSALHHAALNG
  NTELISLLLEAQAAVDIKDNKGMRPLHYAAWQGRKEPMKLVLKAGSAVNIPSDEGHIPLH
  LAAQHGHYDVSEMLLQHQSNPCMVDNSGKTPLDLACEFGRVGVVQLLLSSNMCAALLEPR
  PGDATDPNGTSPLHLAAKNGHIDIIRLLLQAGIDINRQTKSGTALHEAALCGKTEVVRLL
  LDSGINAHVRNTYSQTALDIVHQFTTSQASREIKQLLREASAALQVRATKDYCNNYDLTS
  LNVKAGDIITVLEQHPDGRWKGCIHDNRTGNDRVGYFPSSLGEAIVKRAGSRAGTEPSLP
  QGSSSSGPSAPPEEIWVLRKPFAGGDRSGSISGMAGGRGSGGHALHAGSEGVKLLATVLS
  QKSVSESGPGDSPAKPPEGSAGVARSQPPVAHAGQVYGEQPPKKLEPASEGKSSEAVSQW
  LTAFQLQLYAPNFISAGYDLPTISRMTPEDLTAIGVTKPGHRKKIAAEISGLSIPDWLPE
  HKPANLAVWLSMIGLAQYYKVLVDNGYENIDFITDITWEDLQEIGITKLGHQKKLMLAVR
  KLAELQKAEYAKYEGGPLRRKAPQSLEVMAIESPPPPEPTPADCQSPKMTTFQDSELSDE
  LQAAMTGPAEVGPTTEKPSSHLPPTPRATTRQDSSLGGRARHMSSSQELLGDGPPGPSSP
  MSRSQEYLLDEGPAPGTPPREARPGRHGHSIKRASVPPVPGKPRQVLPPGTSHFTPPQTP
  TKTRPGSPQALGGPHGPAPATAKVKPTPQLLPPTERPMSPRSLPQSPTHRGFAYVLPQPV
  EGEVGPAAPGPAPPPVPTAVPTLCLPPEADAEPGRPKKRAHSLNRYAASDSEPERDELLV
  PAAAGPYATVQRRVGRSHSVRAPAGADKNVNRSQSFAVRPRKKGPPPPPPKRSSSALASA
  NLADEPVPDAEPEDGLLGVRAQCRRASDLAGSVDTGSAGSVKSIAAMLELSSIGGGGRAA
  RRPPEGHPTPRPASPEPGRVATVLASVKHKEAIGPGGEVVNRRRTLSGPVTGLLATARRG
  PGESADPGPFVEDGTGRQRPRGPSKGEAGVEGPPLAKVEASATLKRRIRAKQNQQENVKF
  ILTESDTVKRRPKAKEREAGPEPPPPLSVYHNGTGTVRRRPASEQAGPPELPPPPPPAEP
  PPTDLAHLPPLPPPEGEARKPAKPPVSPKPVLTQPVPKLQGSPTPTSKKVPLPGPGSPEV
  KRAHGTPPPVSPKPPPPPTAPKPVKAVAGLPSGSAGPSPAPSPARQPPAALAKPPGTPPS
  LGASPAKPPSPGAPALHVPAKPPRAAAAAAAAAAAPPAPPEGASPGDSARQKLEETSACL
  AAALQAVEEKIRQEDAQGPRDSAAEKSTGSILDDIGSMFDDLADQLDAMLE
• Function: May link the scaffolding protein CASK to downstream intracellular effectors.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Definitive	Biomarker	[1]
Anxiety disorder	DISBI2BT	Definitive	Biomarker	[1]

3 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 Caskin-1 (CASKIN1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Caskin-1 (CASKIN1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Caskin-1 (CASKIN1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Caskin-1 (CASKIN1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Caskin-1 (CASKIN1).	[6]

References

• [1] Dendritic spine morphology and memory formation depend on postsynaptic Caskin proteins.Sci Rep. 2019 Nov 14;9(1):16843. doi: 10.1038/s41598-019-53317-9.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] 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.
• [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.