Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5HNM8)

DOT Name Submaxillary gland androgen-regulated protein 3B (SMR3B)
Synonyms Proline-rich peptide P-B; Proline-rich protein 3
Gene Name SMR3B
Related Disease
Esophageal squamous cell carcinoma ( )
Uveal Melanoma ( )
Abetalipoproteinemia ( )
Acute lymphocytic leukaemia ( )
Acute monocytic leukemia ( )
Adult glioblastoma ( )
Analgesia ( )
Bone disease ( )
Childhood acute lymphoblastic leukemia ( )
Chordoma ( )
Colorectal carcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Idiopathic cardiomyopathy ( )
Lung cancer ( )
Lung carcinoma ( )
Myeloid leukaemia ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Oral cancer ( )
Prostate neoplasm ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Triple negative breast cancer ( )
Adenocarcinoma ( )
Carcinoma ( )
Colon carcinoma ( )
Neuroblastoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Metastatic malignant neoplasm ( )
Tuberculosis ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Childhood kidney Wilms tumor ( )
Colon cancer ( )
Ductal breast carcinoma in situ ( )
Invasive breast carcinoma ( )
Melanoma ( )
Wilms tumor ( )
UniProt ID
SMR3B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF15621
Sequence
MKSLTWILGLWALAACFTPGESQRGPRGPYPPGPLAPPQPFGPGFVPPPPPPPYGPGRIP
PPPPAPYGPGIFPPPPPQP
Tissue Specificity Secreted into saliva by submaxillary gland. Not expressed in heart, brain, lung, liver, skeletal muscle, Kidney, pancreas or placenta.

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Esophageal squamous cell carcinoma DIS5N2GV Definitive Biomarker [1]
Uveal Melanoma DISA7ZGL Definitive Altered Expression [2]
Abetalipoproteinemia DISMSS7T Strong Biomarker [3]
Acute lymphocytic leukaemia DISPX75S Strong Biomarker [4]
Acute monocytic leukemia DIS28NEL Strong Biomarker [5]
Adult glioblastoma DISVP4LU Strong Biomarker [6]
Analgesia DISK3TVI Strong Biomarker [7]
Bone disease DISE1F82 Strong Altered Expression [8]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [4]
Chordoma DISCHJE7 Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
Glioblastoma multiforme DISK8246 Strong Biomarker [6]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
Idiopathic cardiomyopathy DISUGBZL Strong Biomarker [14]
Lung cancer DISCM4YA Strong Biomarker [15]
Lung carcinoma DISTR26C Strong Biomarker [15]
Myeloid leukaemia DISMN944 Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [10]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [17]
Oral cancer DISLD42D Strong Biomarker [18]
Prostate neoplasm DISHDKGQ Strong Altered Expression [19]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [18]
Stomach cancer DISKIJSX Strong Biomarker [11]
Triple negative breast cancer DISAMG6N Strong Biomarker [20]
Adenocarcinoma DIS3IHTY moderate Altered Expression [21]
Carcinoma DISH9F1N moderate Altered Expression [22]
Colon carcinoma DISJYKUO moderate Altered Expression [23]
Neuroblastoma DISVZBI4 moderate Altered Expression [24]
Prostate cancer DISF190Y moderate Biomarker [19]
Prostate carcinoma DISMJPLE moderate Biomarker [19]
Metastatic malignant neoplasm DIS86UK6 Disputed Altered Expression [25]
Tuberculosis DIS2YIMD Disputed Biomarker [26]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [5]
Breast cancer DIS7DPX1 Limited Altered Expression [27]
Breast carcinoma DIS2UE88 Limited Altered Expression [27]
Childhood kidney Wilms tumor DIS0NMK3 Limited Biomarker [28]
Colon cancer DISVC52G Limited Altered Expression [23]
Ductal breast carcinoma in situ DISLCJY7 Limited Altered Expression [29]
Invasive breast carcinoma DISANYTW Limited Altered Expression [29]
Melanoma DIS1RRCY Limited Biomarker [30]
Wilms tumor DISB6T16 Limited Biomarker [28]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fenfluramine DM0762O Phase 3 Fenfluramine increases the expression of Submaxillary gland androgen-regulated protein 3B (SMR3B). [31]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Submaxillary gland androgen-regulated protein 3B (SMR3B). [33]
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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 affects the methylation of Submaxillary gland androgen-regulated protein 3B (SMR3B). [32]
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References

1 Phosphatase of regenerating liver-3 as a convergent therapeutic target for lymph node metastasis in esophageal squamous cell carcinoma.Int J Cancer. 2010 Aug 1;127(3):543-54. doi: 10.1002/ijc.25082.
2 Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2.Sci Rep. 2019 Feb 28;9(1):2990. doi: 10.1038/s41598-019-39643-y.
3 The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia.Mol Cancer. 2012 Sep 21;11:72. doi: 10.1186/1476-4598-11-72.
4 Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance.Oncotarget. 2017 Dec 13;9(3):3549-3561. doi: 10.18632/oncotarget.23186. eCollection 2018 Jan 9.
5 Non-canonical activation of -catenin by PRL-3 phosphatase in acute myeloid leukemia.Oncogene. 2019 Feb;38(9):1508-1519. doi: 10.1038/s41388-018-0526-3. Epub 2018 Oct 10.
6 PRL-3 is a potential glioblastoma prognostic marker and promotes glioblastoma progression by enhancing MMP7 through the ERK and JNK pathways.Theranostics. 2018 Feb 7;8(6):1527-1539. doi: 10.7150/thno.22699. eCollection 2018.
7 Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif.Am J Physiol Regul Integr Comp Physiol. 2015 Apr 1;308(7):R569-75. doi: 10.1152/ajpregu.00153.2014. Epub 2015 Jan 28.
8 Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.Blood. 2008 Jan 15;111(2):806-15. doi: 10.1182/blood-2007-07-101139. Epub 2007 Oct 12.
9 Upregulation of metastasis-associated PRL-3 initiates chordoma in zebrafish.Int J Oncol. 2016 Apr;48(4):1541-52. doi: 10.3892/ijo.2016.3363. Epub 2016 Jan 29.
10 Interaction with tumorassociated macrophages promotes PRL?induced invasion of colorectal cancer cells via MAPK pathwayinduced EMT and NFB signalinginduced angiogenesis.Oncol Rep. 2019 May;41(5):2790-2802. doi: 10.3892/or.2019.7049. Epub 2019 Mar 7.
11 PRL-3 promotes gastric cancer migration and invasion through a NF-B-HIF-1-miR-210 axis.J Mol Med (Berl). 2016 Apr;94(4):401-15. doi: 10.1007/s00109-015-1350-7. Epub 2015 Nov 9.
12 Upregulation of protein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3) is associated with tumor differentiation and a poor prognosis in human hepatocellular carcinoma.Ann Surg Oncol. 2013 Jan;20(1):305-17. doi: 10.1245/s10434-012-2395-2. Epub 2012 Oct 13.
13 Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway.Med Sci Monit. 2018 Nov 12;24:8105-8114. doi: 10.12659/MSM.913307.
14 Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling.Biochem Biophys Res Commun. 2001 May 25;283(5):1061-8. doi: 10.1006/bbrc.2001.4881.
15 Downregulating PRL-3 inhibit migration and invasion of lung cancer cell via RhoA and mDia1.Tumori. 2012 May-Jun;98(3):370-6. doi: 10.1177/030089161209800315.
16 PRL-3 exerts oncogenic functions in myeloid leukemia cells via aberrant dephosphorylation of stathmin and activation of STAT3 signaling.Aging (Albany NY). 2019 Sep 23;11(18):7817-7829. doi: 10.18632/aging.102290. Epub 2019 Sep 23.
17 PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer.Pathology. 2009 Feb;41(2):118-26. doi: 10.1080/00313020802579268.
18 Increased expression of the PRL-3 gene in human oral squamous cell carcinoma and dysplasia tissues.Asian Pac J Cancer Prev. 2011;12(4):947-51.
19 PRL? increases the aggressive phenotype of prostate cancer cells invitro and its expression correlates with high-grade prostate tumors in patients.Int J Oncol. 2018 Feb;52(2):402-412. doi: 10.3892/ijo.2017.4208. Epub 2017 Nov 20.
20 PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.Cancer Lett. 2016 Oct 1;380(2):505-512. doi: 10.1016/j.canlet.2016.07.017. Epub 2016 Jul 21.
21 High PRL-3 expression in human gastric cancer is a marker of metastasis and grades of malignancies: an in situ hybridization study.Virchows Arch. 2007 Mar;450(3):303-10. doi: 10.1007/s00428-006-0361-8. Epub 2007 Jan 18.
22 PRL-3, an emerging marker of carcinogenesis, is strongly associated with poor prognosis.Anticancer Agents Med Chem. 2011 Jan;11(1):99-108. doi: 10.2174/187152011794941145.
23 WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability.Ann Surg Oncol. 2019 Dec;26(13):4826-4834. doi: 10.1245/s10434-019-07780-3. Epub 2019 Sep 23.
24 Protein tyrosine phosphatase PRL-3 in malignant cells and endothelial cells: expression and function.Mol Cancer Ther. 2006 Feb;5(2):219-29. doi: 10.1158/1535-7163.MCT-05-0289.
25 Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression.Cancer Res. 2010 Nov 1;70(21):8959-67. doi: 10.1158/0008-5472.CAN-10-2041. Epub 2010 Sep 14.
26 Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3.Gene Ther. 2013 Aug;20(8):834-45. doi: 10.1038/gt.2013.5. Epub 2013 Jan 31.
27 PRL-3 promotes breast cancer progression by downregulating p14(ARF)-mediated p53 expression.Oncol Lett. 2018 Mar;15(3):2795-2800. doi: 10.3892/ol.2017.7639. Epub 2017 Dec 19.
28 Expression of phosphatase of regenerating liver-3 is associated with prognosis of Wilms' tumor.Onco Targets Ther. 2017 Jan 10;10:311-317. doi: 10.2147/OTT.S107076. eCollection 2017.
29 Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.Br J Cancer. 2006 Aug 7;95(3):347-54. doi: 10.1038/sj.bjc.6603261. Epub 2006 Jul 11.
30 PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1.J Invest Dermatol. 2015 Sep;135(9):2273-2282. doi: 10.1038/jid.2015.154. Epub 2015 Apr 10.
31 Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
32 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.
33 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.