Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1N2182)

• DOT Name: Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1)
• Gene Name: CAMSAP1
• Related Disease:
  Cortical dysplasia, complex, with other brain malformations 12
  Juvenile idiopathic arthritis
  Laryngeal squamous cell carcinoma
• UniProt ID: CAMP1_HUMAN
• PDB ID: 5M54; 5M5C; 6QUS; 6QVJ
• Pfam ID: PF17095 ; PF11971 ; PF08683
• Sequence:
  MVDASGRAAAEGWRKMEAPPDGAADLVPLDRYDAARAKIAANLQWICAKAYGRDNIPEDL
  RDPFYVDQYEQEHIKPPVIKLLLSSELYCRVCSLILKGDQVAALQGHQSVIQALSRKGIY
  VMESDDTPVTESDLSRAPIKMSAHMAMVDALMMAYTVEMISIEKVVASVKRFSTFSASKE
  LPYDLEDAMVFWINKVNLKMREITEKEVKLKQQLLESPAHQKVRYRREHLSARQSPYFPL
  LEDLMRDGSDGAALLAVIHYYCPEQMKLDDICLKEVTSMADSLYNIRLLREFSNEYLNKC
  FYLTLEDMLYAPLVLKPNVMVFIAELFWWFENVKPDFVQPRDVQELKDAKTVLHQKSSRP
  PVPISNATKRSFLGSPAAGTLAELQPPVQLPAEGCHRHYLHPEEPEYLGKGTAAFSPSHP
  LLPLRQKQQKSIQGEDIPDQRHRSNSLTRVDGQPRGAAIAWPEKKTRPASQPTPFALHHA
  ASCEVDPSSGDSISLARSISKDSLASNIVNLTPQNQPHPTATKSHGKSLLSNVSIEDEEE
  ELVAIVRADVVPQQADPEFPRASPRALGLTANARSPQGQLDTSESKPDSFFLEPLMPAVL
  KPAKEKQVITKEDERGEGRPRSIVSRRPSEGPQPLVRRKMTGSRDLNRTFTPIPCSEFPM
  GIDPTETGPLSVETAGEVCGGPLALGGFDPFPQGPSTDGFFLHVGRADEDTEGRLYVSCS
  KSPNSHDSEPWTLLRQDSDSDVVDIEEAEHDFMGEAHPVVFSRYIGEEESAKLQEDMKVK
  EHEDKDDASGRSSPCLSTASQMSSVSMASGSVKMTSFAERKLQRLNSCETKSSTSSSQKT
  TPDASESCPAPLTTWRQKREQSPSQHGKDPASLLASELVQLHMQLEEKRRAIEAQKKKME
  ALSARQRLKLGKAAFLHVVKKGKAEAAPPLRPEHFAKEYSQHNGEDCGDAVSKTEDFLVK
  EEQREELLHEPQDVDKESLAFAQQHKAKDPVALHELERNKVISAALLEDTVGEVVDVNEC
  DLSIEKLNETISTLQQAILKISQQQEQLLMKSPTVPVPGSKNNSQDHKVKAPVHFVEPLS
  PTGVAGHRKAPRLGQGRNSRSGRPAELKVPKDRPQGSSRSKTPTPSVETLPHLRPFPASS
  HPRTPTDPGLDSALEPSGDPHGKCLFDSYRLHDESNQRTLTLSSSKDANILSEQMSLKEV
  LDASVKEVGSSSSDVSGKESVPVEEPLRSRASLIEVDLSDLKAPDEDGELVSLDGSADLV
  SEGDQKPGVGFFFKDEQKAEDELAKKRAAFLLKQQRKAEEARVRKQQLEAEVELKRDEAR
  RKAEEDRVRKEEEKARRELIKQEYLRRKQQQILEEQGLGKPKSKPKKPRPKSVHREESCS
  DSGTKCSSTPDNLSRTQSGSSLSLASAATTEPESVHSGGTPSQRVESMEALPILSRNPSR
  STDRDWETASAASSLASVAEYTGPKLFKEPSSKSNKPIIHNAISHCCLAGKVNEPHKNSI
  LEELEKCDANHYIILFRDAGCQFRALYCYYPDTEEIYKLTGTGPKNITKKMIDKLYKYSS
  DRKQFNLIPAKTMSVSVDALTIHNHLWQPKRPAVPKKAQTRK
• Function: Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and stabilizes microtubules. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation. Through interaction with spectrin may regulate neurite outgrowth.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cortical dysplasia, complex, with other brain malformations 12	DIS9IWS1	Strong	Autosomal recessive	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[3]

7 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 Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1).	[13]

References

• [1] The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] MicroRNA-126 modulates the tumor microenvironment by targeting calmodulin-regulated spectrin-associated protein 1 (Camsap1).Int J Oncol. 2014 May;44(5):1678-84. doi: 10.3892/ijo.2014.2321. Epub 2014 Mar 5.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] 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.
• [9] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.