Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM7IXDG)

DOT Name	Calbindin (CALB1)
Synonyms	Calbindin D28; D-28K; Vitamin D-dependent calcium-binding protein, avian-type
Gene Name	CALB1
Related Disease	Neurodegeneration with brain iron accumulation 5 ( ) Alzheimer disease ( ) Autism ( ) Cerebral infarction ( ) Depression ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Epilepsy ( ) Epithelial ovarian cancer ( ) Huntington disease ( ) Kidney neoplasm ( ) Malignant mesothelioma ( ) Medulloblastoma ( ) MELAS syndrome ( ) Mental disorder ( ) Multiple endocrine neoplasia ( ) Multiple endocrine neoplasia type 1 ( ) Neoplasm ( ) Nephropathy ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Parkinson disease ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Temporal lobe epilepsy ( ) Varicose veins ( ) Amyotrophic lateral sclerosis ( ) Choriocarcinoma ( ) Diabetic kidney disease ( ) Nervous system disease ( ) Parkinsonian disorder ( ) Renal fibrosis ( ) Type-1/2 diabetes ( ) Cognitive impairment ( ) Hereditary hyperbilirubinemia ( ) Kearns-Sayre syndrome ( ) Lewy body dementia ( ) Myeloproliferative neoplasm ( ) Neuroblastoma ( ) Spinocerebellar ataxia type 6 ( )
UniProt ID	CALB1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6FIE
Pfam ID	PF00036 ; PF13499
Sequence	MAESHLQSSLITASQFFEIWLHFDADGSGYLEGKELQNLIQELQQARKKAGLELSPEMKT FVDQYGQRDDGKIGIVELAHVLPTEENFLLLFRCQQLKSCEEFMKTWRKYDTDHSGFIET EELKNFLKDLLEKANKTVDDTKLAEYTDLMLKLFDSNNDGKLELTEMARLLPVQENFLLK FQGIKMCGKEFNKAFELYDQDGNGYIDENELDALLKDLCEKNKQDLDINNITTYKKNIMA LSDGGKLYRTDLALILCAGDN
Function	Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase.
KEGG Pathway	Endocrine and other factor-regulated calcium reabsorption (hsa04961 )
Reactome Pathway	Amyloid fiber formation (R-HSA-977225 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neurodegeneration with brain iron accumulation 5	DISW9SFJ	Definitive	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[5]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[6]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[6]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Huntington disease	DISQPLA4	Strong	Biomarker	[8]
Kidney neoplasm	DISBNZTN	Strong	Genetic Variation	[9]
Malignant mesothelioma	DISTHJGH	Strong	Altered Expression	[10]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[11]
MELAS syndrome	DIS81Z3S	Strong	Altered Expression	[12]
Mental disorder	DIS3J5R8	Strong	Biomarker	[13]
Multiple endocrine neoplasia	DISZGBKW	Strong	Genetic Variation	[14]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Nephropathy	DISXWP4P	Strong	Biomarker	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[7]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[18]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[5]
Varicose veins	DISIMBN2	Strong	Biomarker	[20]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[21]
Choriocarcinoma	DISDBVNL	moderate	Biomarker	[22]
Diabetic kidney disease	DISJMWEY	Disputed	Biomarker	[23]
Nervous system disease	DISJ7GGT	Disputed	Altered Expression	[24]
Parkinsonian disorder	DISHGY45	Disputed	Biomarker	[25]
Renal fibrosis	DISMHI3I	Disputed	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[23]
Cognitive impairment	DISH2ERD	Limited	Altered Expression	[26]
Hereditary hyperbilirubinemia	DIS788JD	Limited	Biomarker	[27]
Kearns-Sayre syndrome	DIS9UK5R	Limited	Biomarker	[28]
Lewy body dementia	DISAE66J	Limited	Biomarker	[29]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Genetic Variation	[30]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[29]
Spinocerebellar ataxia type 6	DISH7224	Limited	Biomarker	[31]
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⏷ Show the Full List of 41 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

15 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 Calbindin (CALB1).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calbindin (CALB1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calbindin (CALB1).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calbindin (CALB1).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calbindin (CALB1).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Calbindin (CALB1).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Calbindin (CALB1).	[38]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Calbindin (CALB1).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Calbindin (CALB1).	[40]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Calbindin (CALB1).	[41]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Calbindin (CALB1).	[42]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Calbindin (CALB1).	[32]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Calbindin (CALB1).	[43]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Calbindin (CALB1).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calbindin (CALB1).	[45]
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⏷ Show the Full List of 15 Drug(s)

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 increases the methylation of Calbindin (CALB1).	[44]
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References

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17	Proteomic analysis of urinary extracellular vesicles reveal biomarkers for neurologic disease.EBioMedicine. 2019 Jul;45:351-361. doi: 10.1016/j.ebiom.2019.06.021. Epub 2019 Jun 20.
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19	Effect of pre- and post-treatment with Bacopa monnieri (Brahmi) on phencyclidine-induced disruptions in object recognition memory and cerebral calbindin, parvalbumin, and calretinin immunoreactivity in rats.Neuropsychiatr Dis Treat. 2019 May 1;15:1103-1117. doi: 10.2147/NDT.S193222. eCollection 2019.
20	Endogenous Glutamate Excites Myenteric Calbindin Neurons by Activating Group I Metabotropic Glutamate Receptors in the Mouse Colon.Front Neurosci. 2019 May 1;13:426. doi: 10.3389/fnins.2019.00426. eCollection 2019.
21	Expression of calbindin-D28K in motoneuron hybrid cells after retroviral infection with calbindin-D28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity.Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6796-801. doi: 10.1073/pnas.93.13.6796.
22	Calbindin-D28k (CaBP28k) identification and regulation by 1,25-dihydroxyvitamin D3 in human choriocarcinoma cell line JEG-3. Mol Cell Endocrinol. 2005 May 31;236(1-2):31-41. doi: 10.1016/j.mce.2005.03.002. Epub 2005 Apr 12.
23	Role of Calbindin-D28k in Diabetes-Associated Advanced Glycation End-Products-Induced Renal Proximal Tubule Cell Injury.Cells. 2019 Jun 30;8(7):660. doi: 10.3390/cells8070660.
24	Epigenetic suppression of hippocampal calbindin-D28k by FosB drives seizure-related cognitive deficits.Nat Med. 2017 Nov;23(11):1377-1383. doi: 10.1038/nm.4413. Epub 2017 Oct 16.
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26	Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss.Cell Rep. 2017 Oct 24;21(4):891-900. doi: 10.1016/j.celrep.2017.10.006.
27	Changes in calcium-binding protein expression in the auditory brainstem nuclei of the jaundiced Gunn rat.Hear Res. 2002 Sep;171(1-2):129-141. doi: 10.1016/s0378-5955(02)00494-x.
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29	Calcipotriol inhibits -synuclein aggregation in SH-SY5Y neuroblastoma cells by a Calbindin-D28k-dependent mechanism.J Neurochem. 2017 Apr;141(2):263-274. doi: 10.1111/jnc.13971.
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35	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
36	In vitro evaluation of biomarkers for cisplatin-induced nephrotoxicity using HK-2 human kidney epithelial cells. Toxicol Lett. 2013 Mar 13;217(3):235-42. doi: 10.1016/j.toxlet.2012.12.015. Epub 2012 Dec 31.
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