Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQ9UB0)

DOT Name Sperm-associated antigen 11B (SPAG11A)
Synonyms Human epididymis-specific protein 2; He2; Protein EP2; Sperm antigen HE2
Gene Name SPAG11A
Related Disease
Cognitive impairment ( )
Tuberculosis ( )
Alzheimer disease ( )
Asthma ( )
Autosomal dominant polycystic kidney disease ( )
Barrett esophagus ( )
Cerebral infarction ( )
Esophageal adenocarcinoma ( )
Esophageal ulcer ( )
Glaucoma/ocular hypertension ( )
Hyperparathyroidism ( )
Hypotrichosis 7 ( )
Nasal polyp ( )
Neoplasm ( )
Nephritis ( )
Osteoarthritis ( )
Parkinson disease ( )
Polycystic kidney disease ( )
Status epilepticus seizure ( )
Stroke ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Coronary heart disease ( )
Ductal breast carcinoma in situ ( )
Hepatocellular carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
UniProt ID
SG11B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF05324
Sequence
MRQRLLPSVTSLLLVALLFPGSSQARHVNHSATEALGELRERAPGQGTNGFQLLRHAVKR
DLLPPRTPPYQVHISHREARGPSFRICVDFLGPRWARGCSTGN
Function Has antimicrobial activity against E.coli. Plays a role in the defense response in the male reproductive tract, contributing to sperm maturation, storage and protection.
Tissue Specificity
Specifically expressed in caput and proximal corpus of epididymis (at protein level) . Present in the epididymal epithelium and on the sperm surface, with a subacrosomal equatorial distribution on the sperm head (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cognitive impairment DISH2ERD Definitive Biomarker [1]
Tuberculosis DIS2YIMD Definitive Genetic Variation [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Asthma DISW9QNS Strong Genetic Variation [4]
Autosomal dominant polycystic kidney disease DISBHWUI Strong Biomarker [5]
Barrett esophagus DIS416Y7 Strong Altered Expression [6]
Cerebral infarction DISR1WNP Strong Biomarker [7]
Esophageal adenocarcinoma DISODWFP Strong Altered Expression [6]
Esophageal ulcer DISNUPWL Strong Altered Expression [8]
Glaucoma/ocular hypertension DISLBXBY Strong Biomarker [9]
Hyperparathyroidism DIS4FVAT Strong Biomarker [10]
Hypotrichosis 7 DISDFBQ5 Strong Altered Expression [11]
Nasal polyp DISLP3XE Strong Altered Expression [12]
Neoplasm DISZKGEW Strong Biomarker [13]
Nephritis DISQZQ70 Strong Biomarker [14]
Osteoarthritis DIS05URM Strong Biomarker [15]
Parkinson disease DISQVHKL Strong Biomarker [16]
Polycystic kidney disease DISWS3UY Strong Biomarker [5]
Status epilepticus seizure DISY3BIC Strong Biomarker [17]
Stroke DISX6UHX Strong Biomarker [7]
Advanced cancer DISAT1Z9 moderate Biomarker [18]
Amyotrophic lateral sclerosis DISF7HVM moderate Altered Expression [19]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [20]
Ductal breast carcinoma in situ DISLCJY7 moderate Genetic Variation [21]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [22]
Prostate cancer DISF190Y Limited Biomarker [23]
Prostate carcinoma DISMJPLE Limited Biomarker [23]
Rheumatoid arthritis DISTSB4J Limited Biomarker [24]
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⏷ Show the Full List of 28 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 Sperm-associated antigen 11B (SPAG11A). [25]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Sperm-associated antigen 11B (SPAG11A). [26]
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References

1 Impaired lipid metabolism markers to assess the risk of neuroinflammation in autism spectrum disorder.Metab Brain Dis. 2018 Aug;33(4):1141-1153. doi: 10.1007/s11011-018-0206-6. Epub 2018 Mar 22.
2 Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis.Infect Genet Evol. 2016 Dec;46:23-27. doi: 10.1016/j.meegid.2016.10.016. Epub 2016 Oct 22.
3 Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease.J Neurosci. 2005 Nov 2;25(44):10180-7. doi: 10.1523/JNEUROSCI.3591-05.2005.
4 Polymorphisms in the prostaglandin E2 receptor subtype 2 gene confer susceptibility to aspirin-intolerant asthma: a candidate gene approach. Hum Mol Genet. 2004 Dec 15;13(24):3203-17. doi: 10.1093/hmg/ddh332. Epub 2004 Oct 20.
5 EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells.Am J Physiol Renal Physiol. 2007 Nov;293(5):F1622-32. doi: 10.1152/ajprenal.00036.2007. Epub 2007 Aug 29.
6 Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma.Aliment Pharmacol Ther. 2010 Feb 1;31(3):440-51. doi: 10.1111/j.1365-2036.2009.04172.x. Epub 2009 Oct 16.
7 PGE(2) signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia.Proc Natl Acad Sci U S A. 2019 May 14;116(20):10019-10024. doi: 10.1073/pnas.1818544116. Epub 2019 Apr 29.
8 Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of prostaglandin EP2 receptors, cAMP, and pCREB.Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G602-10. doi: 10.1152/ajpgi.00177.2014. Epub 2014 Jul 24.
9 Omidenepag isopropyl for the treatment of glaucoma and ocular hypertension.Drugs Today (Barc). 2019 Jun;55(6):377-384. doi: 10.1358/dot.2019.55.6.2984806.
10 Prostaglandin E2 receptor EP2 mediates the effect of cyclooxygenase 2 on secondary parathyroid hyperplasia in end-stage renal disease.Nephrol Dial Transplant. 2019 Apr 1;34(4):606-617. doi: 10.1093/ndt/gfy194.
11 Expression of arachidonate metabolism enzymes and receptors in nasal polyps of aspirin-hypersensitive asthmatics.Int Arch Allergy Immunol. 2012;157(4):354-62. doi: 10.1159/000329744. Epub 2011 Nov 24.
12 Impaired E Prostanoid2 Expression and Resistance to Prostaglandin E2 in Nasal Polyp Fibroblasts from Subjects with Aspirin-Exacerbated Respiratory Disease.Am J Respir Cell Mol Biol. 2016 Jan;54(1):34-40. doi: 10.1165/rcmb.2014-0486OC.
13 Prostaglandin EP2 receptor: Novel therapeutic target for human cancers (Review).Int J Mol Med. 2018 Sep;42(3):1203-1214. doi: 10.3892/ijmm.2018.3744. Epub 2018 Jun 26.
14 Upregulation of cyclooxygenase-1 and the PGE2 receptor EP2 in rat and human mesangioproliferative glomerulonephritis.Inflamm Res. 2000 Jul;49(7):345-54. doi: 10.1007/PL00000215.
15 Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes.Ann Rheum Dis. 2011 Jan;70(1):221-6. doi: 10.1136/ard.2009.118620. Epub 2010 Sep 24.
16 Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons.Mol Neurobiol. 2018 Jun;55(6):4763-4776. doi: 10.1007/s12035-017-0681-5. Epub 2017 Jul 17.
17 A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition.Neurobiol Dis. 2020 Jan;133:104399. doi: 10.1016/j.nbd.2019.02.010. Epub 2019 Feb 25.
18 Peripherally Restricted, Highly Potent, Selective, Aqueous-Soluble EP2 Antagonist with Anti-Inflammatory Properties.Mol Pharm. 2018 Dec 3;15(12):5809-5817. doi: 10.1021/acs.molpharmaceut.8b00764. Epub 2018 Nov 15.
19 Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.Neurochem Int. 2018 Oct;119:132-139. doi: 10.1016/j.neuint.2017.06.013. Epub 2017 Jul 4.
20 Common polymorphisms of cyclooxygenase-2 and prostaglandin E2 receptor and increased risk for acute coronary syndrome in coronary artery disease.Thromb Haemost. 2008 Nov;100(5):893-8.
21 Epigenetic mechanisms regulate the prostaglandin E receptor 2 in breast cancer.J Steroid Biochem Mol Biol. 2012 Nov;132(3-5):331-8. doi: 10.1016/j.jsbmb.2012.07.007. Epub 2012 Aug 19.
22 PGE(2) synthesis and signaling in malignant transformation and progression of human hepatocellular carcinoma.Hum Pathol. 2017 May;63:120-127. doi: 10.1016/j.humpath.2017.02.018. Epub 2017 Mar 12.
23 Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation.J Pharmacol Exp Ther. 2013 Feb;344(2):360-7. doi: 10.1124/jpet.112.200444. Epub 2012 Nov 28.
24 Prostaglandin E2 differentially modulates proinflammatory/prodestructive effects of TNF-alpha on synovial fibroblasts via specific E prostanoid receptors/cAMP.J Immunol. 2009 Jul 15;183(2):1328-36. doi: 10.4049/jimmunol.0900801. Epub 2009 Jun 19.
25 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.
26 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.