Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6F8IAL)

DOT Name	Napsin-A (NAPSA)
Synonyms	EC 3.4.23.-; Aspartyl protease 4; ASP4; Asp 4; Napsin-1; TA01/TA02
Gene Name	NAPSA
Related Disease	Adult glioblastoma ( ) Glioblastoma multiforme ( ) Type-1/2 diabetes ( ) Alzheimer disease ( ) Anaplastic large cell lymphoma ( ) Astrocytoma ( ) B-cell lymphoma ( ) Carcinoid tumor ( ) Carcinoma ( ) Classic Hodgkin lymphoma ( ) Clear cell adenocarcinoma ( ) Endometrial carcinoma ( ) Epithelial ovarian cancer ( ) Follicular lymphoma ( ) Intestinal disorder ( ) Irritable bowel syndrome ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Lung neoplasm ( ) Lung squamous cell carcinoma ( ) Lymphoma ( ) Malignant soft tissue neoplasm ( ) Mesothelioma ( ) Minimally invasive lung adenocarcinoma ( ) Mucinous adenocarcinoma ( ) Ovarian cancer ( ) Pancreatic adenocarcinoma ( ) Papillary renal cell carcinoma ( ) Plasma cell myeloma ( ) Primary cutaneous peripheral T-cell lymphoma not otherwise specified ( ) Psoriasis ( ) Renal cell carcinoma ( ) Sarcoma ( ) Thyroid gland carcinoma ( ) Thyroid tumor ( ) Triple negative breast cancer ( ) Neuroendocrine cancer ( ) Small-cell lung cancer ( ) Squamous cell carcinoma ( ) Endometrium neoplasm ( ) Non-small-cell lung cancer ( )
UniProt ID	NAPSA_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.4.23.-
Pfam ID	PF00026
Sequence	MSPPPLLQPLLLLLPLLNVEPSGATLIRIPLHRVQPGRRILNLLRGWREPAELPKLGAPS PGDKPIFVPLSNYRDVQYFGEIGLGTPPQNFTVAFDTGSSNLWVPSRRCHFFSVPCWLHH RFDPKASSSFQANGTKFAIQYGTGRVDGILSEDKLTIGGIKGASVIFGEALWEPSLVFAF AHFDGILGLGFPILSVEGVRPPMDVLVEQGLLDKPVFSFYLNRDPEEPDGGELVLGGSDP AHYIPPLTFVPVTVPAYWQIHMERVKVGPGLTLCAKGCAAILDTGTSLITGPTEEIRALH AAIGGIPLLAGEYIILCSEIPKLPAVSFLLGGVWFNLTAHDYVIQTTRNGVRLCLSGFQA LDVPPPAGPFWILGDVFLGTYVAVFDRGDMKSSARVGLARARTRGADLGWGETAQAQFPG
Function	May be involved in processing of pneumocyte surfactant precursors.
Tissue Specificity	Expressed predominantly in adult lung (type II pneumocytes) and kidney and in fetal lung. Low levels in adult spleen and very low levels in peripheral blood leukocytes.
KEGG Pathway	Lysosome (hsa04142 )
Reactome Pathway	Surfactant metabolism (R-HSA-5683826 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[4]
Carcinoid tumor	DISMNRDC	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[4]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Biomarker	[8]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Follicular lymphoma	DISVEUR6	Strong	Altered Expression	[4]
Intestinal disorder	DISGPMUQ	Strong	Genetic Variation	[11]
Irritable bowel syndrome	DIS27206	Strong	Genetic Variation	[11]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[15]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[16]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[17]
Mesothelioma	DISKWK9M	Strong	Biomarker	[18]
Minimally invasive lung adenocarcinoma	DIS4W83X	Strong	Biomarker	[19]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Genetic Variation	[20]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Altered Expression	[4]
Psoriasis	DIS59VMN	Strong	Altered Expression	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Sarcoma	DISZDG3U	Strong	Altered Expression	[17]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[12]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[12]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[22]
Neuroendocrine cancer	DISVGJET	moderate	Altered Expression	[23]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[25]
Endometrium neoplasm	DIS6OS2L	Disputed	Altered Expression	[26]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Altered Expression	[27]
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⏷ Show the Full List of 42 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

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 affects the expression of Napsin-A (NAPSA).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Napsin-A (NAPSA).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Napsin-A (NAPSA).	[30]
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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 Napsin-A (NAPSA).	[31]
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References

1	KAP regulates ROCK2 and Cdk2 in an RNA-activated glioblastoma invasion pathway.Oncogene. 2015 Mar 12;34(11):1432-41. doi: 10.1038/onc.2014.49. Epub 2014 Apr 7.
2	Knowledge, attitude and practice among non-ophthalmic health care providers regarding eye management of diabetics in private sector of Riyadh, Saudi Arabia.BMC Health Serv Res. 2019 Jun 13;19(1):375. doi: 10.1186/s12913-019-4216-9.
3	Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.Gene. 2001 Jun 27;271(2):159-69. doi: 10.1016/s0378-1119(01)00521-2.
4	Aberrant expression of napsin A in a subset of malignant lymphomas.Histol Histopathol. 2016 Feb;31(2):213-21. doi: 10.14670/HH-11-669. Epub 2015 Sep 24.
5	Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP increases proliferation and migration in glioblastoma.Cancer Res. 2007 Jan 1;67(1):130-8. doi: 10.1158/0008-5472.CAN-06-2478.
6	Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: napsin A expression and genomic alterations.Mod Pathol. 2018 Jan;31(1):111-121. doi: 10.1038/modpathol.2017.110. Epub 2017 Sep 8.
7	High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations.Int J Gynecol Pathol. 2019 Jan;38 Suppl 1(Iss 1 Suppl 1):S40-S63. doi: 10.1097/PGP.0000000000000491.
8	Napsin A and WT 1 are useful immunohistochemical markers for differentiating clear cell carcinoma ovary from high-grade serous carcinoma.APMIS. 2018 Jan;126(1):45-55. doi: 10.1111/apm.12784. Epub 2017 Nov 20.
9	Comparative Use of Napsin A and Glypican 3 to Distinguish Endometrial Clear Cell from Serous and Endometrioid Carcinomas.Int J Gynecol Cancer. 2018 Sep;28(7):1318-1324. doi: 10.1097/IGC.0000000000001303.
10	Napsin-A, a Possible Diagnostic Marker for Differentiating Clear Cell Ovarian Carcinoma From Other High-grade Ovarian Carcinomas.Appl Immunohistochem Mol Morphol. 2018 Sep;26(8):605-610. doi: 10.1097/PAI.0000000000000510.
11	21st century research in urban WASH and health in sub-Saharan Africa: methods and outcomes in transition.Int J Environ Health Res. 2019 Aug;29(4):457-478. doi: 10.1080/09603123.2018.1550193. Epub 2018 Dec 13.
12	Napsin A Expression in Subtypes of Thyroid Tumors: Comparison with Lung Adenocarcinomas.Endocr Pathol. 2020 Mar;31(1):39-45. doi: 10.1007/s12022-019-09600-6.
13	Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer.Sci Rep. 2019 Feb 4;9(1):1319. doi: 10.1038/s41598-018-37722-0.
14	Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases.Hum Pathol. 2019 Feb;84:221-230. doi: 10.1016/j.humpath.2018.10.009. Epub 2018 Oct 31.
15	Lung recurrence and its therapeutic strategy in patients with pancreatic cancer.Pancreatology. 2020 Jan;20(1):89-94. doi: 10.1016/j.pan.2019.11.015. Epub 2019 Nov 26.
16	Combined Immunohistochemistry after Mass Spectrometry Imaging for Superior Spatial Information.Proteomics Clin Appl. 2019 Jan;13(1):e1800035. doi: 10.1002/prca.201800035. Epub 2018 Aug 21.
17	EGFR, KRAS, BRAF and ALK gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype.Eur Respir J. 2014 Mar;43(3):872-83. doi: 10.1183/09031936.00018013. Epub 2013 Aug 29.
18	Biomarkers in the diagnosis of pleural diseases: a 2018 update.Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808660. doi: 10.1177/1753466618808660.
19	Applications and limitations of immunohistochemical expression of "Napsin-A" in distinguishing lung adenocarcinoma from adenocarcinomas of other organs.Appl Immunohistochem Mol Morphol. 2013 May;21(3):191-5. doi: 10.1097/PAI.0b013e3182612643.
20	KRAS mutational analysis and immunohistochemical studies can help distinguish pancreatic metastases from primary lung adenocarcinomas.Mod Pathol. 2014 Feb;27(2):262-70. doi: 10.1038/modpathol.2013.146. Epub 2013 Jul 26.
21	Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ.J Invest Dermatol. 1991 Jul;97(1):73-9. doi: 10.1111/1523-1747.ep12478128.
22	SOX10, GATA3, GCDFP15, Androgen Receptor, and Mammaglobin for the Differential Diagnosis Between Triple-negative Breast Cancer and TTF1-negative Lung Adenocarcinoma.Am J Surg Pathol. 2019 Mar;43(3):293-302. doi: 10.1097/PAS.0000000000001216.
23	Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.Appl Immunohistochem Mol Morphol. 2013 Jul;21(4):292-7. doi: 10.1097/PAI.0b013e31826fd4f3.
24	Utility of TTF-1 and Napsin-A in the work-up of malignant effusions.Diagn Cytopathol. 2016 Apr;44(4):299-304. doi: 10.1002/dc.23442. Epub 2016 Jan 22.
25	The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung.Ups J Med Sci. 2020 Feb;125(1):19-29. doi: 10.1080/03009734.2019.1692101. Epub 2019 Dec 6.
26	Infrequent Immunohistochemical Expression of Napsin A in Endometrial Carcinomas.Appl Immunohistochem Mol Morphol. 2017 Oct;25(9):632-638. doi: 10.1097/PAI.0000000000000350.
27	Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.J Exp Clin Cancer Res. 2019 Mar 11;38(1):122. doi: 10.1186/s13046-019-1124-0.
28	Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
29	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
30	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.
31	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.