Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8S7RUG)

DOT Name Prokineticin-1 (PROK1)
Synonyms Endocrine-gland-derived vascular endothelial growth factor; EG-VEGF; Mambakine
Gene Name PROK1
Related Disease
Advanced cancer ( )
Age-related macular degeneration ( )
Bacterial infection ( )
Carcinoma ( )
Choriocarcinoma ( )
Choroidal neovascularization ( )
Colon cancer ( )
Colon carcinoma ( )
Complete hydatidiform mole ( )
Eclampsia ( )
Endometriosis ( )
Graves disease ( )
Hepatocellular carcinoma ( )
Hirschsprung disease ( )
Hyperinsulinemia ( )
Mesothelioma ( )
Metastatic malignant neoplasm ( )
Metastatic prostate carcinoma ( )
Ovarian hyperstimulation syndrome ( )
Ovarian serous adenocarcinoma ( )
Plasma cell myeloma ( )
Polycystic ovarian syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
Colorectal carcinoma ( )
Hypertension, pregnancy-induced ( )
Neoplasm ( )
Pancreatic cancer ( )
Adrenal adenoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Endometrium neoplasm ( )
UniProt ID
PROK1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF06607
Sequence
MRGATRVSIMLLLVTVSDCAVITGACERDVQCGAGTCCAISLWLRGLRMCTPLGREGEEC
HPGSHKVPFFRKRKHHTCPCLPNLLCSRFPDGRYRCSMDLKNINF
Function
Potently contracts gastrointestinal (GI) smooth muscle. Induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. Has little or no effect on a variety of other endothelial and non-endothelial cell types. Induces proliferation and differentiation, but not migration, of enteric neural crest cells. Directly influences neuroblastoma progression by promoting the proliferation and migration of neuroblastoma cells. Positively regulates PTGS2 expression and prostaglandin synthesis. May play a role in placentation. May play a role in normal and pathological testis angiogenesis.
Tissue Specificity
Localizes to glandular epithelium, stroma and vascular epithelial cells of first trimester decidua (at protein level). Up-regulated in first trimester decidua when compared with non-pregnant endometrium. Expressed in the steroidogenic glands, ovary, testis, adrenal and placenta.
Reactome Pathway
G alpha (q) signalling events (R-HSA-416476 )
Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Age-related macular degeneration DIS0XS2C Strong Biomarker [2]
Bacterial infection DIS5QJ9S Strong Biomarker [3]
Carcinoma DISH9F1N Strong Biomarker [4]
Choriocarcinoma DISDBVNL Strong Biomarker [5]
Choroidal neovascularization DISLGVL7 Strong Altered Expression [2]
Colon cancer DISVC52G Strong Biomarker [6]
Colon carcinoma DISJYKUO Strong Biomarker [6]
Complete hydatidiform mole DIS5QPI0 Strong Biomarker [5]
Eclampsia DISWPO8U Strong Biomarker [7]
Endometriosis DISX1AG8 Strong Altered Expression [8]
Graves disease DISU4KOQ Strong Altered Expression [9]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [10]
Hirschsprung disease DISUUSM1 Strong Genetic Variation [11]
Hyperinsulinemia DISIDWT6 Strong Biomarker [7]
Mesothelioma DISKWK9M Strong Biomarker [4]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [1]
Metastatic prostate carcinoma DISVBEZ9 Strong Biomarker [1]
Ovarian hyperstimulation syndrome DIS4L94Y Strong Biomarker [12]
Ovarian serous adenocarcinoma DISSU72Z Strong Altered Expression [4]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [13]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [14]
Prostate cancer DISF190Y Strong Biomarker [15]
Prostate carcinoma DISMJPLE Strong Biomarker [15]
Prostate neoplasm DISHDKGQ Strong Altered Expression [16]
Thyroid cancer DIS3VLDH Strong Biomarker [9]
Thyroid gland carcinoma DISMNGZ0 Strong Biomarker [9]
Thyroid gland papillary carcinoma DIS48YMM Strong Altered Expression [9]
Thyroid tumor DISLVKMD Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 moderate Altered Expression [17]
Hypertension, pregnancy-induced DISHNU25 moderate Biomarker [18]
Neoplasm DISZKGEW moderate Biomarker [19]
Pancreatic cancer DISJC981 moderate Posttranslational Modification [19]
Adrenal adenoma DISC2UN8 Limited Altered Expression [20]
Endometrial cancer DISW0LMR Limited Biomarker [21]
Endometrial carcinoma DISXR5CY Limited Biomarker [21]
Endometrium neoplasm DIS6OS2L Limited Biomarker [21]
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⏷ Show the Full List of 37 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
[3H]cAMP DMZRQU7 Investigative Prokineticin-1 (PROK1) affects the response to substance of [3H]cAMP. [27]
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4 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 Prokineticin-1 (PROK1). [22]
Triclosan DMZUR4N Approved Triclosan increases the expression of Prokineticin-1 (PROK1). [23]
Progesterone DMUY35B Approved Progesterone increases the expression of Prokineticin-1 (PROK1). [24]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Prokineticin-1 (PROK1). [25]
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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 Prokineticin-1 (PROK1). [26]
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References

1 PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells.Oncotarget. 2014 Dec 30;5(24):12646-64. doi: 10.18632/oncotarget.2653.
2 Choroidal neovascularization in transgenic mice expressing prokineticin 1: an animal model for age-related macular degeneration.Mol Ther. 2006 Mar;13(3):609-16. doi: 10.1016/j.ymthe.2005.08.024. Epub 2005 Nov 2.
3 Prokineticin 1 induces inflammatory response in human myometrium: a potential role in initiating term and preterm parturition.Am J Pathol. 2011 Dec;179(6):2709-19. doi: 10.1016/j.ajpath.2011.08.029. Epub 2011 Oct 6.
4 PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma.Hum Pathol. 2009 Oct;40(10):1434-40. doi: 10.1016/j.humpath.2009.02.008. Epub 2009 May 7.
5 Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.Clin Cancer Res. 2017 Nov 15;23(22):7130-7140. doi: 10.1158/1078-0432.CCR-17-0811. Epub 2017 Sep 12.
6 Endocrine gland-derived vascular endothelial growth factor strengthens cell invasion ability via prokineticin receptor 2 in colon cancer cell lines.Oncol Rep. 2013 Feb;29(2):459-63. doi: 10.3892/or.2012.2124. Epub 2012 Nov 6.
7 Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells.J Cell Mol Med. 2018 Jan;22(1):163-172. doi: 10.1111/jcmm.13305. Epub 2017 Aug 7.
8 Prokineticin 1, homeobox A10, and progesterone receptor messenger ribonucleic acid expression in primary cultures of endometrial stromal cells isolated from endometrium of healthy women and from eutopic endometrium of women with endometriosis.Fertil Steril. 2010 Dec;94(7):2558-63. doi: 10.1016/j.fertnstert.2010.03.006. Epub 2010 Apr 18.
9 Upregulation of endocrine gland-derived vascular endothelial growth factor in papillary thyroid cancers displaying infiltrative patterns, lymph node metastases, and BRAF mutation.Thyroid. 2011 Apr;21(4):391-9. doi: 10.1089/thy.2010.0168.
10 Correlation of four vascular specific growth factors with carcinogenesis and portal vein tumor thrombus formation in human hepatocellular carcinoma.J Exp Clin Cancer Res. 2006 Sep;25(3):403-9.
11 Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.J Hum Genet. 2012 Aug;57(8):485-93. doi: 10.1038/jhg.2012.54. Epub 2012 May 31.
12 High levels of soluble vascular endothelial growth factor receptor 1/sFlt1 and low levels of vascular endothelial growth factor in follicular fluid on the day of oocyte retrieval correlate with ovarian hyperstimulation syndrom regardless of the stimulation protocol.J Physiol Pharmacol. 2017 Jun;68(3):477-484.
13 Prokineticin-1/endocrine gland-derived vascular endothelial growth factor is a survival factor for human multiple myeloma cells.Leuk Lymphoma. 2010 Oct;51(10):1902-12. doi: 10.3109/10428194.2010.512963.
14 miR?8?p suppresses cell proliferation and weakens the progression of polycystic ovary syndrome by targeting prokineticin?.Mol Med Rep. 2019 Sep;20(3):2468-2475. doi: 10.3892/mmr.2019.10446. Epub 2019 Jul 1.
15 Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer.Oncotarget. 2015 Sep 22;6(28):26437-56. doi: 10.18632/oncotarget.4664.
16 A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer.EMBO J. 2003 Jan 15;22(2):270-80. doi: 10.1093/emboj/cdg023.
17 Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor PROKR2 are associated to human colorectal cancer progression and peritoneal carcinomatosis.Cancer Biomark. 2018 Feb 6;21(2):345-354. doi: 10.3233/CBM-170499.
18 EG-VEGF Maintenance Over Early Gestation to Develop a Pregnancy-Induced Hypertensive Animal Model.Methods Mol Biol. 2018;1710:317-324. doi: 10.1007/978-1-4939-7498-6_25.
19 EG-VEGF silencing inhibits cell proliferation and promotes cell apoptosis in pancreatic carcinoma via PI3K/AKT/mTOR signaling pathway.Biomed Pharmacother. 2019 Jan;109:762-769. doi: 10.1016/j.biopha.2018.10.125. Epub 2018 Nov 5.
20 Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.Horm Cancer. 2015 Dec;6(5-6):225-36. doi: 10.1007/s12672-015-0236-z.
21 Endocrine gland-derived vascular endothelial growth factor is expressed in human peri-implantation endometrium, but not in endometrial carcinoma.Endocrinology. 2006 Jan;147(1):88-95. doi: 10.1210/en.2005-0543. Epub 2005 Oct 6.
22 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.
23 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
24 Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
25 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
26 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.
27 Prokineticin 1 induces Dickkopf 1 expression and regulates cell proliferation and decidualization in the human endometrium. Mol Hum Reprod. 2011 Oct;17(10):626-36. doi: 10.1093/molehr/gar031. Epub 2011 May 5.