Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HOGPQ)

DOT Name Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2)
Synonyms NAALADase L2
Gene Name NAALADL2
Related Disease
Behcet disease ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Advanced cancer ( )
Endometriosis ( )
Prostate cancer ( )
Prostate neoplasm ( )
Venous thromboembolism ( )
Proliferative diabetic retinopathy ( )
Prostate carcinoma ( )
UniProt ID
NADL2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF04389
Sequence
MGENEASLPNTSLQGKKMAYQKVHADQRAPGHSQYLDNDDLQATALDLEWDMEKELEESG
FDQFQLDGAENQNLGHSETIDLNLDSIQPATSPKGRFQRLQEESDYITHYTRSAPKSNRC
NFCHVLKILCTATILFIFGILIGYYVHTNCPSDAPSSGTVDPQLYQEILKTIQAEDIKKS
FRNLVQLYKNEDDMEISKKIKTQWTSLGLEDVQFVNYSVLLDLPGPSPSTVTLSSSGQCF
HPNGQPCSEEARKDSSQDLLYSYAAYSAKGTLKAEVIDVSYGMADDLKRIRKIKNVTNQI
ALLKLGKLPLLYKLSSLEKAGFGGVLLYIDPCDLPKTVNPSHDTFMVSLNPGGDPSTPGY
PSVDESFRQSRSNLTSLLVQPISAPLVAKLISSPKARTKNEACSSLELPNNEIRVVSMQV
QTVTKLKTVTNVVGFVMGLTSPDRYIIVGSHHHTAHSYNGQEWASSTAIITAFIRALMSK
VKRGWRPDRTIVFCSWGGTAFGNIGSYEWGEDFKKVLQKNVVAYISLHSPIRGNSSLYPV
ASPSLQQLVVEKNNFNCTRRAQCPETNISSIQIQGDADYFINHLGVPIVQFAYEDIKTLE
GPSFLSEARFSTRATKIEEMDPSFNLHETITKLSGEVILQIANEPVLPFNALDIALEVQN
NLKGDQPNTHQLLAMALRLRESAELFQSDEMRPANDPKERAPIRIRMLNDILQDMEKSFL
VKQAPPGFYRNILYHLDEKTSRFSILIEAWEHCKPLASNETLQEALSEVLNSINSAQVYF
KAGLDVFKSVLDGKN
Function May be catalytically inactive.
Tissue Specificity Expressed at higher level in kidney and placenta. In embryo, it is mainly confined to duodenal and stomach endoderm, mesonephros, metanephros and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Behcet disease DISSYMBS Strong Altered Expression [1]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [2]
Ovarian cancer DISZJHAP Strong Genetic Variation [2]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [2]
Advanced cancer DISAT1Z9 moderate Altered Expression [3]
Endometriosis DISX1AG8 moderate Genetic Variation [4]
Prostate cancer DISF190Y moderate Biomarker [3]
Prostate neoplasm DISHDKGQ moderate Altered Expression [3]
Venous thromboembolism DISUR7CR moderate Genetic Variation [5]
Proliferative diabetic retinopathy DISQZ13G Limited Genetic Variation [6]
Prostate carcinoma DISMJPLE Limited Genetic Variation [7]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2). [8]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Rofecoxib DM3P5DA Approved Rofecoxib decreases the expression of Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2). [11]
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References

1 Identification of genetic susceptibility loci for intestinal Behet's disease.Sci Rep. 2017 Jan 3;7:39850. doi: 10.1038/srep39850.
2 Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers.Eur J Hum Genet. 2017 Apr;25(4):432-438. doi: 10.1038/ejhg.2016.203. Epub 2017 Feb 1.
3 N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 is overexpressed in cancer and promotes a pro-migratory and pro-metastatic phenotype.Oncogene. 2014 Nov 6;33(45):5274-87. doi: 10.1038/onc.2013.464. Epub 2013 Nov 18.
4 Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.Hum Reprod. 2017 Apr 1;32(4):780-793. doi: 10.1093/humrep/dex024.
5 A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.BMC Med Genet. 2013 Mar 20;14:36. doi: 10.1186/1471-2350-14-36.
6 Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.Diabetes. 2019 Feb;68(2):441-456. doi: 10.2337/db18-0567. Epub 2018 Nov 28.
7 Two susceptibility loci identified for prostate cancer aggressiveness.Nat Commun. 2015 May 5;6:6889. doi: 10.1038/ncomms7889.
8 Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
9 Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
10 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
11 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.