Details of Drug Off-Target (DOT)

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

• DOT Name: Calcium-binding protein 1 (CABP1)
• Synonyms: CaBP1; Calbrain; Caldendrin
• Gene Name: CABP1
• Related Disease:
  Glioblastoma multiforme
  Depression
  Neoplasm
  Schizophrenia
  Temporal lobe epilepsy
• UniProt ID: CABP1_HUMAN
• PDB ID: 2K7B; 2K7C; 2K7D; 2LAN; 2LAP; 3OX5; 3OX6
• Pfam ID: PF13499
• Sequence:
  MGGGDGAAFKRPGDGARLQRVLGLGSRREPRSLPAGGPAPRRTAPPPPGHASAGPAAMSS
  HIAKSESKTSLLKAAAAAASGGSRAPRHGPARDPGLPSRRLPGSCPATPQSSGDPSSRRP
  LCRPAPREEGARGSQRVLPQAHCRPREALPAAASRPSPSSPLPPARGRDGEERGLSPALG
  LRGSLRARGRGDSVPAAASEADPFLHRLRPMLSSAFGQDRSLRPEEIEELREAFREFDKD
  KDGYINCRDLGNCMRTMGYMPTEMELIELSQQINMNLGGHVDFDDFVELMGPKLLAETAD
  MIGVKELRDAFREFDTNGDGEISTSELREAMRKLLGHQVGHRDIEEIIRDVDLNGDGRVD
  FEEFVRMMSR
• Function: Modulates calcium-dependent activity of inositol 1,4,5-triphosphate receptors (ITPRs). Inhibits agonist-induced intracellular calcium signaling. Enhances inactivation and does not support calcium-dependent facilitation of voltage-dependent P/Q-type calcium channels. Causes calcium-dependent facilitation and inhibits inactivation of L-type calcium channels by binding to the same sites as calmodulin in the C-terminal domain of CACNA1C, but has an opposite effect on channel function. Suppresses the calcium-dependent inactivation of CACNA1D. Inhibits TRPC5 channels. Prevents NMDA receptor-induced cellular degeneration. Required for the normal transfer of light signals through the retina.
• Tissue Specificity: Retina and brain. Somatodendritic compartment of neurons. Calbrain was found exclusively in brain where it is abundant in the hippocampus, habenular area in the epithalamus and in the cerebellum.
• Reactome Pathway: Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[5]

2 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 Calcium-binding protein 1 (CABP1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcium-binding protein 1 (CABP1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcium-binding protein 1 (CABP1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calcium-binding protein 1 (CABP1).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Calcium-binding protein 1 (CABP1).	[10]

References

• [1] Identification of key candidate genes and pathways in glioblastoma by integrated bioinformatical analysis.Exp Ther Med. 2019 Nov;18(5):3439-3449. doi: 10.3892/etm.2019.7975. Epub 2019 Sep 5.
• [2] Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels.J Neurosci. 2018 May 2;38(18):4430-4440. doi: 10.1523/JNEUROSCI.0022-18.2018. Epub 2018 Apr 13.
• [3] Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study.Mol Carcinog. 2017 Oct;56(10):2258-2266. doi: 10.1002/mc.22678. Epub 2017 Jun 15.
• [4] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [5] Kainate-induced epileptic seizures induce a recruitment of caldendrin to the postsynaptic density in rat brain.Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):159-62. doi: 10.1016/s0169-328x(03)00235-3.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.