Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH719AH)

DOT Name Prolactin-inducible protein (PIP)
Synonyms Gross cystic disease fluid protein 15; GCDFP-15; Prolactin-induced protein; Secretory actin-binding protein; SABP; gp17
Gene Name PIP
Related Disease
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Arthritis ( )
Atypical teratoid/rhabdoid tumour ( )
Bacteremia ( )
Breast fibrocystic disease ( )
Breast neoplasm ( )
Carcinoid tumor ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Dermatomyositis ( )
Hypospadias ( )
Immunodeficiency ( )
Intellectual disability ( )
Keratoconus ( )
Lung neoplasm ( )
Male infertility ( )
Mucinous adenocarcinoma ( )
Neoplasm ( )
Neuroblastoma ( )
Oculocerebrorenal syndrome ( )
Polyp ( )
Prostate adenocarcinoma ( )
Prostate carcinoma ( )
Pulmonary fibrosis ( )
Renal cell carcinoma ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Synovitis ( )
Tuberculosis ( )
Acute otitis media ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Cardiovascular disease ( )
Invasive breast carcinoma ( )
Lung adenocarcinoma ( )
Metastatic sarcoma ( )
Otitis media ( )
Prostate cancer ( )
Triple negative breast cancer ( )
Arthrogryposis ( )
Digestive system neoplasm ( )
GNE myopathy ( )
Metastatic malignant neoplasm ( )
Sinusitis ( )
UniProt ID
PIP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3ES6
Pfam ID
PF05326
Sequence
MRLLQLLFRASPATLLLVLCLQLGANKAQDNTRKIIIKNFDIPKSVRPNDEVTAVLAVQT
ELKECMVVKTYLISSIPLQGAFNYKYTACLCDDNPKTFYWDFYTNRTVQIAAVVDVIREL
GICPDDAAVIPIKNNRFYTIEILKVE
Tissue Specificity Expressed in pathological conditions of the mammary gland and in several exocrine tissues, such as the lacrimal, salivary, and sweat glands.
Reactome Pathway
Miscellaneous transport and binding events (R-HSA-5223345 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Arthritis DIST1YEL Strong Genetic Variation [3]
Atypical teratoid/rhabdoid tumour DIS1FA0D Strong Biomarker [4]
Bacteremia DIS6N9RZ Strong Biomarker [5]
Breast fibrocystic disease DISUM7ID Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Carcinoid tumor DISMNRDC Strong Genetic Variation [8]
Carcinoma DISH9F1N Strong Altered Expression [9]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [10]
Dermatomyositis DIS50C5O Strong Genetic Variation [11]
Hypospadias DIS48CCP Strong Altered Expression [12]
Immunodeficiency DIS093I0 Strong Biomarker [1]
Intellectual disability DISMBNXP Strong Genetic Variation [13]
Keratoconus DISOONXH Strong Altered Expression [14]
Lung neoplasm DISVARNB Strong Biomarker [8]
Male infertility DISY3YZZ Strong Genetic Variation [15]
Mucinous adenocarcinoma DISKNFE8 Strong Biomarker [16]
Neoplasm DISZKGEW Strong Altered Expression [17]
Neuroblastoma DISVZBI4 Strong Biomarker [18]
Oculocerebrorenal syndrome DIS8TEDY Strong Biomarker [19]
Polyp DISRSLYF Strong Biomarker [20]
Prostate adenocarcinoma DISBZYU8 Strong Altered Expression [21]
Prostate carcinoma DISMJPLE Strong Altered Expression [22]
Pulmonary fibrosis DISQKVLA Strong Biomarker [23]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [10]
Small-cell lung cancer DISK3LZD Strong Biomarker [18]
Squamous cell carcinoma DISQVIFL Strong Genetic Variation [8]
Synovitis DISW2GPY Strong Biomarker [24]
Tuberculosis DIS2YIMD Strong Biomarker [25]
Acute otitis media DISL8D8G moderate Biomarker [26]
Arteriosclerosis DISK5QGC moderate Biomarker [27]
Atherosclerosis DISMN9J3 moderate Biomarker [27]
Cardiovascular disease DIS2IQDX moderate Biomarker [27]
Invasive breast carcinoma DISANYTW moderate Biomarker [28]
Lung adenocarcinoma DISD51WR moderate Biomarker [29]
Metastatic sarcoma DISKYC7V moderate Altered Expression [30]
Otitis media DISGZDUO moderate Biomarker [26]
Prostate cancer DISF190Y moderate Altered Expression [22]
Triple negative breast cancer DISAMG6N moderate Biomarker [29]
Arthrogryposis DISC81CM Disputed Biomarker [31]
Digestive system neoplasm DISPOJCT Limited Genetic Variation [32]
GNE myopathy DIS73X4W Limited Genetic Variation [33]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [34]
Sinusitis DISX5NCF Limited Biomarker [35]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Prolactin-inducible protein (PIP). [36]
Hydroxyflutamide DMGIZF5 Approved Hydroxyflutamide decreases the expression of Prolactin-inducible protein (PIP). [36]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Prolactin-inducible protein (PIP). [36]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Prolactin-inducible protein (PIP). [37]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Prolactin-inducible protein (PIP). [39]
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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 Prolactin-inducible protein (PIP). [38]
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References

1 Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression.Sci Rep. 2018 Sep 13;8(1):13741. doi: 10.1038/s41598-018-32205-8.
2 GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15.Diagn Pathol. 2017 Jul 10;12(1):51. doi: 10.1186/s13000-017-0638-z.
3 Polymyalgia rheumatica can be distinguished from late onset rheumatoid arthritis at baseline: results of a 5-yr prospective study.Rheumatology (Oxford). 2009 Feb;48(2):123-7. doi: 10.1093/rheumatology/ken343. Epub 2008 Nov 2.
4 Identification of a novel biomarker for pyridoxine-dependent epilepsy: Implications for newborn screening.J Inherit Metab Dis. 2019 May;42(3):565-574. doi: 10.1002/jimd.12059. Epub 2019 Mar 11.
5 Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial.Clin Infect Dis. 2019 Nov 27;69(12):2045-2056. doi: 10.1093/cid/ciz181.
6 PIP/GCDFP-15 gene expression and apocrine differentiation in carcinomas of the breast.Virchows Arch. 1994;425(5):459-65. doi: 10.1007/BF00197548.
7 The diagnosis of a metastatic breast tumor from ovarian cancer by the succession of a p53 mutation: a case report.World J Surg Oncol. 2017 Jun 29;15(1):117. doi: 10.1186/s12957-017-1185-5.
8 GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors.Appl Immunohistochem Mol Morphol. 2009 Dec;17(6):505-11. doi: 10.1097/PAI.0b013e3181a8e809.
9 Prolactin-induced protein (PIP)-characterization and role in breast cancer progression.Am J Cancer Res. 2018 Nov 1;8(11):2150-2164. eCollection 2018.
10 Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma.Int J Oncol. 2013 Nov;43(5):1441-6. doi: 10.3892/ijo.2013.2073. Epub 2013 Aug 21.
11 Variation at HLA-DPB1 is associated with dermatomyositis in Chinese population.J Dermatol. 2016 Nov;43(11):1307-1313. doi: 10.1111/1346-8138.13397. Epub 2016 May 6.
12 Association of prolactin-induced protein with preputial development of hypospadias.BJU Int. 2012 Mar;109(6):926-32. doi: 10.1111/j.1464-410X.2011.10467.x. Epub 2011 Aug 25.
13 Dent Disease with mutations in OCRL1. Am J Hum Genet. 2005 Feb;76(2):260-7. doi: 10.1086/427887. Epub 2004 Dec 30.
14 Prolactin-Induced Protein is a novel biomarker for Keratoconus.Exp Eye Res. 2019 Feb;179:55-63. doi: 10.1016/j.exer.2018.10.015. Epub 2018 Oct 26.
15 Male infertility-linked point mutation disrupts the Ca2+ oscillation-inducing and PIP(2) hydrolysis activity of sperm PLC.Biochem J. 2011 Mar 1;434(2):211-7. doi: 10.1042/BJ20101772.
16 Expression of hormone receptors, adipophilin, and GCDFP-15 in mucinous carcinoma of the skin.J Cutan Pathol. 2018 Dec;45(12):886-890. doi: 10.1111/cup.13349. Epub 2018 Oct 4.
17 Albumin-Binding PSMA Ligands: Implications for Expanding the Therapeutic Window.J Nucl Med. 2019 May;60(5):656-663. doi: 10.2967/jnumed.118.221150. Epub 2018 Dec 14.
18 Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells.Int J Cancer. 1995 Jan 17;60(2):216-20. doi: 10.1002/ijc.2910600215.
19 The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization.Am J Hum Genet. 2002 Dec;71(6):1420-7. doi: 10.1086/344517. Epub 2002 Nov 11.
20 Topographic gene expression in the sinonasal cavity of patients with chronic sinusitis with polyps.Otolaryngol Head Neck Surg. 2011 Jul;145(1):171-5. doi: 10.1177/0194599811402030.
21 Expression of the prolactin-inducible protein (PIP/GCDFP15) gene in benign epithelium and adenocarcinoma of the prostate.Cancer Sci. 2004 Jun;95(6):491-5. doi: 10.1111/j.1349-7006.2004.tb03238.x.
22 Extramammary Paget Disease of the Scrotum: A Contemporary Clinicopathologic Analysis of 20 Cases in the United States.Appl Immunohistochem Mol Morphol. 2020 Aug;28(7):524-531. doi: 10.1097/PAI.0000000000000789.
23 Histological hallmarks and role of Slug/PIP axis in pulmonary hypertension secondary to pulmonary fibrosis.EMBO Mol Med. 2019 Sep;11(9):e10061. doi: 10.15252/emmm.201810061. Epub 2019 Aug 29.
24 Flares in rheumatoid arthritis: do patient-reported swollen and tender joints match clinical and ultrasonography findings?.Rheumatology (Oxford). 2020 Jan 1;59(1):129-136. doi: 10.1093/rheumatology/kez231.
25 Tuberculosis case finding: Supplement intensified case finding among acute lower respiratory infection (ALRI) hospitalized patients in Sa Kaeo province, Thailand.J Formos Med Assoc. 2019 Aug;118(8):1255-1265. doi: 10.1016/j.jfma.2018.11.016. Epub 2019 Jan 10.
26 The prolactin inducible protein/gross cystic disease fluid protein-15 deficient mice develop anomalies in lymphoid organs.Immunobiology. 2019 Nov;224(6):811-816. doi: 10.1016/j.imbio.2019.08.005. Epub 2019 Aug 13.
27 Gypenoside XVII prevents atherosclerosis by attenuating endothelial apoptosis and oxidative stress: insight into the ERalpha-mediated PI3K/Akt pathway. Int J Mol Sci. 2017 Feb 9;18(2). pii: E77.
28 Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes.J Clin Pathol. 2017 Nov;70(11):926-934. doi: 10.1136/jclinpath-2016-204137. Epub 2017 Apr 20.
29 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.
30 Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue.Pathobiology. 1994;62(2):82-9. doi: 10.1159/000163882.
31 Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 2007 Sep;81(3):530-9. doi: 10.1086/520771. Epub 2007 Jul 24.
32 Expression of unusual immunohistochemical markers in mucinous breast carcinoma.Acta Histochem. 2017 Apr;119(3):327-336. doi: 10.1016/j.acthis.2017.03.002. Epub 2017 Mar 21.
33 (18)F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.J Med Chem. 2018 May 10;61(9):4256-4262. doi: 10.1021/acs.jmedchem.8b00240. Epub 2018 Apr 20.
34 The role of histopathologic testing on apocrine carcinoma of the breast.Curr Probl Cancer. 2020 Apr;44(2):100501. doi: 10.1016/j.currproblcancer.2019.100501. Epub 2019 Sep 7.
35 Gene expression profiling of nasal polyps associated with chronic sinusitis and aspirin-sensitive asthma.Laryngoscope. 2008 May;118(5):881-9. doi: 10.1097/MLG.0b013e31816b4b6f.
36 Regulation of GCDFP-15 expression in human mammary cancer cells. Int J Mol Med. 1999 Aug;4(2):135-40. doi: 10.3892/ijmm.4.2.135.
37 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
38 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.
39 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.