Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5G9V94)

DOT Name Double C2-like domain-containing protein alpha (DOC2A)
Synonyms Doc2; Doc2-alpha
Gene Name DOC2A
Related Disease
Adenocarcinoma ( )
Advanced cancer ( )
Atrial fibrillation ( )
Bladder cancer ( )
Complete hydatidiform mole ( )
Gestational trophoblastic neoplasia ( )
Neoplasm ( )
Pancreatic adenocarcinoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Tarsal-carpal coalition syndrome ( )
Transitional cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Urothelial carcinoma ( )
Choriocarcinoma ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Temporal lobe epilepsy ( )
UniProt ID
DOC2A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4MJJ
Pfam ID
PF00168
Sequence
MRGRRGDRMTINIQEHMAINVCPGPIRPIRQISDYFPRGPGPEGGGGGGGEAPAHLVPLA
LAPPAALLGATTPEDGAEVDSYDSDDATALGTLEFDLLYDRASCTLHCSILRAKGLKPMD
FNGLADPYVKLHLLPGACKANKLKTKTQRNTLNPVWNEDLTYSGITDDDITHKVLRIAVC
DEDKLSHNEFIGEIRVPLRRLKPSQKKHFNICLERQVPLASPSSMSAALRGISCYLKELE
QAEQGQGLLEERGRILLSLSYSSRRRGLLVGILRCAHLAAMDVNGYSDPYVKTYLRPDVD
KKSKHKTCVKKKTLNPEFNEEFFYEIELSTLATKTLEVTVWDYDIGKSNDFIGGVSLGPG
ARGEARKHWSDCLQQPDAALERWHTLTSELPPAAGALSSA
Function
Calcium sensor which most probably regulates fusion of vesicles with membranes. Binds calcium and phospholipids. May be involved in calcium dependent neurotransmitter release through the interaction with UNC13A. May be involved in calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.
Tissue Specificity Predominantly expressed in brain. Also expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Atrial fibrillation DIS15W6U Strong Biomarker [3]
Bladder cancer DISUHNM0 Strong Altered Expression [4]
Complete hydatidiform mole DIS5QPI0 Strong Altered Expression [5]
Gestational trophoblastic neoplasia DIS4EJNA Strong Altered Expression [5]
Neoplasm DISZKGEW Strong Biomarker [6]
Pancreatic adenocarcinoma DISKHX7S Strong Altered Expression [1]
Pancreatic cancer DISJC981 Strong Altered Expression [1]
Prostate cancer DISF190Y Strong Biomarker [2]
Prostate carcinoma DISMJPLE Strong Biomarker [2]
Tarsal-carpal coalition syndrome DISY90L2 Strong Altered Expression [7]
Transitional cell carcinoma DISWVVDR Strong Altered Expression [8]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [4]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [4]
Urothelial carcinoma DISRTNTN Strong Altered Expression [8]
Choriocarcinoma DISDBVNL Limited Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [1]
Ovarian cancer DISZJHAP Limited Biomarker [1]
Ovarian neoplasm DISEAFTY Limited Biomarker [1]
Temporal lobe epilepsy DISNOPXX Limited Biomarker [9]
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⏷ Show the Full List of 21 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Double C2-like domain-containing protein alpha (DOC2A). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Double C2-like domain-containing protein alpha (DOC2A). [13]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Double C2-like domain-containing protein alpha (DOC2A). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Double C2-like domain-containing protein alpha (DOC2A). [12]
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References

1 Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.Lab Invest. 2001 Jun;81(6):863-73. doi: 10.1038/labinvest.3780295.
2 The role of DOC-2/DAB2 in modulating androgen receptor-mediated cell growth via the nongenomic c-Src-mediated pathway in normal prostatic epithelium and cancer.Cancer Res. 2005 Nov 1;65(21):9906-13. doi: 10.1158/0008-5472.CAN-05-1481.
3 Effectiveness of the Chest Strap Electrocardiogram to Detect Atrial Fibrillation.Am J Cardiol. 2019 May 15;123(10):1643-1648. doi: 10.1016/j.amjcard.2019.02.028. Epub 2019 Feb 23.
4 Estrogen receptor promotes bladder cancer growth and invasion via alteration of miR-92a/DAB2IP signals.Exp Mol Med. 2018 Nov 20;50(11):1-11. doi: 10.1038/s12276-018-0155-5.
5 DOC-2/hDab2, a candidate tumor suppressor gene involved in the development of gestational trophoblastic diseases.Oncogene. 1998 Jul 30;17(4):419-24. doi: 10.1038/sj.onc.1201955.
6 Smurf1 regulation of DAB2IP controls cell proliferation and migration.Oncotarget. 2016 May 3;7(18):26057-69. doi: 10.18632/oncotarget.8424.
7 Synergistic induction of DOC-2/DAB2 gene expression in transitional cell carcinoma in the presence of GATA6 and histone deacetylase inhibitor.Cancer Res. 2005 Jul 15;65(14):6089-96. doi: 10.1158/0008-5472.CAN-04-3672.
8 Loss of DAB2IP expression in human urothelial carcinoma is associated with poorer recurrence-free survival.Virchows Arch. 2016 Jun;468(6):733-40. doi: 10.1007/s00428-016-1924-y. Epub 2016 Mar 22.
9 Increased expression of DOC2A in human and rat temporal lobe epilepsy.Epilepsy Res. 2019 Mar;151:78-84. doi: 10.1016/j.eplepsyres.2019.02.008. Epub 2019 Feb 25.
10 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
11 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
12 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.
13 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.