Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWXZN5I)

DOT Name cAMP-regulated phosphoprotein 21 (ARPP21)
Synonyms ARPP-21; Thymocyte cAMP-regulated phosphoprotein
Gene Name ARPP21
Related Disease
Acute lymphocytic leukaemia ( )
Childhood acute lymphoblastic leukemia ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Diabetic retinopathy ( )
Gonorrhea ( )
Inherited retinal dystrophy ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Mood disorder ( )
Myocardial infarction ( )
Neoplasm ( )
Retinitis pigmentosa ( )
Breast cancer ( )
Breast carcinoma ( )
Amyotrophic lateral sclerosis ( )
Intellectual disability ( )
UniProt ID
ARP21_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF01424 ; PF12752
Sequence
MSEQGDLNQAIAEEGGTEQETATPENGIVKSESLDEEEKLELQRRLEAQNQERRKSKSGA
GKGKLTRSLAVCEESSARPGGESLQDQESIHLQLSSFSSLQEEDKSRKDDSEREKEKDKN
KDKTSEKPKIRMLSKDCSQEYTDSTGIDLHEFLINTLKNNSRDRMILLKMEQEIIDFIAD
NNNHYKKFPQMSSYQRMLVHRVAAYFGLDHNVDQTGKSVIINKTSSTRIPEQRFCEHLKD
EKGEESQKRFILKRDNSSIDKEDNQQNRMHPFRDDRRSKSIEEREEEYQRVRERIFAHDS
VCSQESLFVENSRLLEDSNICNETYKKRQLFRGNRDGSGRTSGSRQSSSENELKWSDHQR
AWSSTDSDSSNRNLKPAMTKTASFGGITVLTRGDSTSSTRSTGKLSKAGSESSSSAGSSG
SLSRTHPPLQSTPLVSGVAAGSPGCVPYPENGIGGQVAPSSTSYILLPLEAATGIPPGSI
LLNPHTGQPFVNPDGTPAIYNPPTSQQPLRSAMVGQSQQQPPQQQPSPQPQQQVQPPQPQ
MAGPLVTQRDDVATQFGQMTLSRQSSGETPEPPSGPVYPSSLMPQPAQQPSYVIASTGQQ
LPTGGFSGSGPPISQQVLQPPPSPQGFVQQPPPAQMPVYYYPSGQYPTSTTQQYRPMAPV
QYNAQRSQQMPQAAQQAGYQPVLSGQQGFQGLIGVQQPPQSQNVINNQQGTPVQSVMVSY
PTMSSYQVPMTQGSQGLPQQSYQQPIMLPNQAGQGSLPATGMPVYCNVTPPTPQNNLRLI
GPHCPSSTVPVMSASCRTNCASMSNAGWQVKF
Function Isoform 2 may act as a competitive inhibitor of calmodulin-dependent enzymes such as calcineurin in neurons.
Tissue Specificity Isoform 2 is expressed in brain. Isoform 1 is present in immature thymocytes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [1]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [1]
Coronary atherosclerosis DISKNDYU Strong Biomarker [2]
Coronary heart disease DIS5OIP1 Strong Biomarker [2]
Diabetic retinopathy DISHGUJM Strong Biomarker [3]
Gonorrhea DISQ5AO6 Strong Biomarker [4]
Inherited retinal dystrophy DISGGL77 Strong Genetic Variation [5]
Lung cancer DISCM4YA Strong Altered Expression [6]
Lung carcinoma DISTR26C Strong Altered Expression [6]
Major depressive disorder DIS4CL3X Strong Genetic Variation [7]
Mood disorder DISLVMWO Strong Genetic Variation [7]
Myocardial infarction DIS655KI Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [8]
Retinitis pigmentosa DISCGPY8 Strong Genetic Variation [9]
Breast cancer DIS7DPX1 moderate Biomarker [10]
Breast carcinoma DIS2UE88 moderate Biomarker [10]
Amyotrophic lateral sclerosis DISF7HVM Limited Autosomal dominant [11]
Intellectual disability DISMBNXP Limited Genetic Variation [12]
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⏷ Show the Full List of 18 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of cAMP-regulated phosphoprotein 21 (ARPP21). [13]
Testosterone DM7HUNW Approved Testosterone decreases the expression of cAMP-regulated phosphoprotein 21 (ARPP21). [14]
AM251 DMTAWHL Investigative AM251 increases the expression of cAMP-regulated phosphoprotein 21 (ARPP21). [17]
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2 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 decreases the methylation of cAMP-regulated phosphoprotein 21 (ARPP21). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of cAMP-regulated phosphoprotein 21 (ARPP21). [16]
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References

1 ETV6/RUNX1-like acute lymphoblastic leukemia: A novel B-cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype.Genes Chromosomes Cancer. 2017 Aug;56(8):608-616. doi: 10.1002/gcc.22464. Epub 2017 May 5.
2 Outcome after revascularisation of acute myocardial infarction with cardiogenic shock on extracorporeal life support.EuroIntervention. 2018 Apr 6;13(18):e2160-e2168. doi: 10.4244/EIJ-D-17-01014.
3 TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.Mol Metab. 2018 Mar;9:156-167. doi: 10.1016/j.molmet.2018.01.003. Epub 2018 Jan 5.
4 Evaluation of the Digene Hybrid Capture II Assay with the Rapid Capture System for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.J Clin Microbiol. 2002 Oct;40(10):3558-64. doi: 10.1128/JCM.40.10.3558-3564.2002.
5 MERTK mutation update in inherited retinal diseases.Hum Mutat. 2018 Jul;39(7):887-913. doi: 10.1002/humu.23431. Epub 2018 May 23.
6 MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function.Cell Death Differ. 2012 Jun;19(6):1038-48. doi: 10.1038/cdd.2011.190. Epub 2011 Dec 23.
7 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
8 Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.J Oncol. 2018 Nov 1;2018:4518935. doi: 10.1155/2018/4518935. eCollection 2018.
9 Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats.Invest Ophthalmol Vis Sci. 2012 Apr 6;53(4):1895-904. doi: 10.1167/iovs.11-8831.
10 Loss of SNAIL regulated miR-128-2 on chromosome 3p22.3 targets multiple stem cell factors to promote transformation of mammary epithelial cells.Cancer Res. 2012 Nov 15;72(22):6036-50. doi: 10.1158/0008-5472.CAN-12-1507. Epub 2012 Sep 26.
11 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
12 Interstitial deletion of 3p22.3p22.2 encompassing ARPP21 and CLASP2 is a potential pathogenic factor for a syndromic form of intellectual disability: a co-morbidity model with additional copy number variations in a large family.Am J Med Genet A. 2013 Nov;161A(11):2890-3. doi: 10.1002/ajmg.a.36257. Epub 2013 Oct 11.
13 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
14 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
15 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.
16 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.
17 Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.