Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAJF6QN)

• DOT Name: Calcium-dependent secretion activator 1 (CADPS)
• Synonyms: Calcium-dependent activator protein for secretion 1; CAPS-1
• Gene Name: CADPS
• Related Disease:
  Autism spectrum disorder
  Open-angle glaucoma
  Colorectal carcinoma
• UniProt ID: CAPS1_HUMAN
• PDB ID: 1WI1
• Pfam ID: PF06292 ; PF00169
• Sequence:
  MLDPSSSEEESDEIVEEESGKEVLGSAPSGARLSPSRTSEGSAGSAGLGGGGAGAGAGVG
  AGGGGGSGASSGGGAGGLQPSSRAGGGRPSSPSPSVVSEKEKEELERLQKEEEERKKRLQ
  LYVFVMRCIAYPFNAKQPTDMARRQQKISKQQLQTVKDRFQAFLNGETQIMADEAFMNAV
  QSYYEVFLKSDRVARMVQSGGCSANDSREVFKKHIEKRVRSLPEIDGLSKETVLSSWMAK
  FDAIYRGEEDPRKQQARMTASAASELILSKEQLYEMFQNILGIKKFEHQLLYNACQLDNP
  DEQAAQIRRELDGRLQMADQIARERKFPKFVSKEMENMYIEELKSSVNLLMANLESMPVS
  KGGEFKLQKLKRSHNASIIDMGEESENQLSKSDVVLSFSLEVVIMEVQGLKSLAPNRIVY
  CTMEVEGGEKLQTDQAEASKPTWGTQGDFSTTHALPAVKVKLFTESTGVLALEDKELGRV
  ILHPTPNSPKQSEWHKMTVSKNCPDQDLKIKLAVRMDKPQNMKHSGYLWAIGKNVWKRWK
  KRFFVLVQVSQYTFAMCSYREKKAEPQELLQLDGYTVDYTDPQPGLEGGRAFFNAVKEGD
  TVIFASDDEQDRILWVQAMYRATGQSHKPVPPTQVQKLNAKGGNVPQLDAPISQFYADRA
  QKHGMDEFISSNPCNFDHASLFEMVQRLTLDHRLNDSYSCLGWFSPGQVFVLDEYCARNG
  VRGCHRHLCYLRDLLERAENGAMIDPTLLHYSFAFCASHVHGNRPDGIGTVTVEEKERFE
  EIKERLRVLLENQITHFRYCFPFGRPEGALKATLSLLERVLMKDIVTPVPQEEVKTVIRK
  CLEQAALVNYSRLSEYAKIEENQKDAENVGRLITPAKKLEDTIRLAELVIEVLQQNEEHH
  AEPHVDKGEAFAWWSDLMVEHAETFLSLFAVDMDAALEVQPPDTWDSFPLFQLLNDFLRT
  DYNLCNGKFHKHLQDLFAPLVVRYVDLMESSIAQSIHRGFERESWEPVKSLTSNLPNVNL
  PNVNLPKVPNLPVNIPLGIPQMPTFSAPSWMAAIYDADNGSGTSEDLFWKLDALQTFIRD
  LHWPEEEFGKHLEQRLKLMASDMIESCVKRTRIAFEVKLQKTSRSTDFRVPQSICTMFNV
  MVDAKAQSTKLCSMEMGQEHQYHSKIDELIEETVKEMITLLVAKFVTILEGVLAKLSRYD
  EGTLFSSFLSFTVKAASKYVDVPKPGMDVADAYVTFVRHSQDVLRDKVNEEMYIERLFDQ
  WYNSSMNVICTWLTDRMDLQLHIYQLKTLIRMVKKTYRDFRLQGVLDSTLNSKTYETIRN
  RLTVEEATASVSEGGGLQGISMKDSDEEDEEDD
• Function: Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering.
• Tissue Specificity: Specifically expressed in neural and endocrine secretory tissues. Expressed in brain and pancreas and at low level in heart. Also expressed in fetal heart, cerebellum, cerebral cortex, medulla, occipital pole, frontal and temporal lobes, and putamen, as well as weak expression in spinal cord.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[1]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Calcium-dependent secretion activator 1 (CADPS).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calcium-dependent secretion activator 1 (CADPS).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcium-dependent secretion activator 1 (CADPS).	[12]

1 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 Calcium-dependent secretion activator 1 (CADPS).	[10]

References

• [1] Identification of common genetic risk variants for autism spectrum disorder.Nat Genet. 2019 Mar;51(3):431-444. doi: 10.1038/s41588-019-0344-8. Epub 2019 Feb 25.
• [2] Genome-wide association study of primary open angle glaucoma risk and quantitative traits.Mol Vis. 2012;18:1083-92. Epub 2012 Apr 28.
• [3] CAPS1 promotes colorectal cancer metastasis via Snail mediated epithelial mesenchymal transformation.Oncogene. 2019 Jun;38(23):4574-4589. doi: 10.1038/s41388-019-0740-7. Epub 2019 Feb 11.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] 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.
• [12] 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.