Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBWBWW7)

DOT Name Dentin matrix acidic phosphoprotein 1 (DMP1)
Synonyms DMP-1; Dentin matrix protein 1
Gene Name DMP1
Related Disease
Hypophosphatemic rickets, autosomal recessive, 1 ( )
Adenocarcinoma ( )
Arthritis ( )
Bone disease ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colonic neoplasm ( )
Diabetic kidney disease ( )
Epithelial ovarian cancer ( )
Hantavirus infection ( )
Hyperthyroidism ( )
Hypophosphatemic rickets, autosomal recessive, 2 ( )
Hypothyroidism ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant peripheral nerve sheath tumor ( )
Metabolic disorder ( )
Minimally invasive lung adenocarcinoma ( )
Neoplasm ( )
Obstructive sleep apnea ( )
Osteoarthritis ( )
Osteochondrodysplasia ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Periodontitis ( )
Primary hyperparathyroidism ( )
Rickets ( )
Skeletal dysplasia ( )
Soft tissue neoplasm ( )
Squamous cell carcinoma ( )
Vitamin D deficiency ( )
Vitamin D-dependent rickets, type 2 ( )
X-linked dominant hypophosphatemic rickets ( )
X-linked hypophosphatemic rickets ( )
Advanced cancer ( )
Carcinoma ( )
Hypophosphatemic rickets ( )
Lung neoplasm ( )
Autosomal recessive hypophosphatemic rickets ( )
Non-insulin dependent diabetes ( )
Acute myelogenous leukaemia ( )
Ankylosing spondylitis ( )
Chronic kidney disease ( )
Dental caries ( )
Diphtheria ( )
Pachyonychia congenita 3 ( )
Rheumatic fever ( )
UniProt ID
DMP1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07263
Sequence
MKISILLMFLWGLSCALPVTRYQNNESEDSEEWKGHLAQAPTPPLESSESSEGSKVSSEE
QANEDPSDSTQSEEGLGSDDHQYIYRLAGGFSRSTGKGGDDKDDDEDDSGDDTFGDDDSG
PGPKDRQEGGNSRLGSDEDSDDTIQASEESAPQGQDSAQDTTSESRELDNEDRVDSKPEG
GDSTQESESEEHWVGGGSDGESSHGDGSELDDEGMQSDDPESIRSERGNSRMNSAGMKSK
ESGENSEQANTQDSGGSQLLEHPSRKIFRKSRISEEDDRSELDDNNTMEEVKSDSTENSN
SRDTGLSQPRRDSKGDSQEDSKENLSQEESQNVDGPSSESSQEANLSSQENSSESQEEVV
SESRGDNPDPTTSYVEDQEDSDSSEEDSSHTLSHSKSESREEQADSESSESLNFSEESPE
SPEDENSSSQEGLQSHSSSAESQSEESHSEEDDSDSQDSSRSKEDSNSTESKSSSEEDGQ
LKNIEIESRKLTVDAYHNKPIGDQDDNDCQDGY
Function
May have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts, unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite.
Tissue Specificity Expressed in tooth particularly in odontoblast, ameloblast and cementoblast.
KEGG Pathway
ECM-receptor interaction (hsa04512 )
Reactome Pathway
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 )
Post-translational protein phosphorylation (R-HSA-8957275 )
ECM proteoglycans (R-HSA-3000178 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hypophosphatemic rickets, autosomal recessive, 1 DISCIMGJ Definitive Autosomal recessive [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Arthritis DIST1YEL Strong Biomarker [3]
Bone disease DISE1F82 Strong Genetic Variation [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Breast neoplasm DISNGJLM Strong Biomarker [6]
Colonic neoplasm DISSZ04P Strong Biomarker [7]
Diabetic kidney disease DISJMWEY Strong Biomarker [8]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [9]
Hantavirus infection DISZFTMH Strong Biomarker [10]
Hyperthyroidism DISX87ZH Strong Genetic Variation [11]
Hypophosphatemic rickets, autosomal recessive, 2 DISG98UR Strong Biomarker [12]
Hypothyroidism DISR0H6D Strong Genetic Variation [11]
Lung cancer DISCM4YA Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [13]
Malignant peripheral nerve sheath tumor DIS0JTN6 Strong Altered Expression [14]
Metabolic disorder DIS71G5H Strong Biomarker [15]
Minimally invasive lung adenocarcinoma DIS4W83X Strong Altered Expression [2]
Neoplasm DISZKGEW Strong Biomarker [16]
Obstructive sleep apnea DIS0SVD1 Strong Altered Expression [17]
Osteoarthritis DIS05URM Strong Genetic Variation [18]
Osteochondrodysplasia DIS9SPWW Strong Genetic Variation [19]
Ovarian cancer DISZJHAP Strong Altered Expression [9]
Ovarian neoplasm DISEAFTY Strong Altered Expression [9]
Periodontitis DISI9JOI Strong Biomarker [20]
Primary hyperparathyroidism DISB4U1Q Strong Altered Expression [21]
Rickets DISH89YF Strong Biomarker [22]
Skeletal dysplasia DIS5Z8U6 Strong Genetic Variation [19]
Soft tissue neoplasm DISP2OHE Strong Altered Expression [14]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [23]
Vitamin D deficiency DISAWKYI Strong Biomarker [22]
Vitamin D-dependent rickets, type 2 DISZHFC3 Strong Genetic Variation [24]
X-linked dominant hypophosphatemic rickets DISU3OP6 Strong Genetic Variation [24]
X-linked hypophosphatemic rickets DISFTLIR Strong Genetic Variation [24]
Advanced cancer DISAT1Z9 moderate Biomarker [25]
Carcinoma DISH9F1N moderate Genetic Variation [26]
Hypophosphatemic rickets DIS7XTW5 moderate Genetic Variation [24]
Lung neoplasm DISVARNB moderate Biomarker [27]
Autosomal recessive hypophosphatemic rickets DIS8E3KA Supportive Autosomal recessive [28]
Non-insulin dependent diabetes DISK1O5Z Disputed Biomarker [29]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [30]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [31]
Chronic kidney disease DISW82R7 Limited Biomarker [32]
Dental caries DISRBCMD Limited Biomarker [33]
Diphtheria DISZWM55 Limited Genetic Variation [34]
Pachyonychia congenita 3 DISZLC6C Limited Altered Expression [35]
Rheumatic fever DISLUF66 Limited Altered Expression [36]
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⏷ Show the Full List of 48 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
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Dentin matrix acidic phosphoprotein 1 (DMP1). [37]
Phosphate DMUXQG7 Approved Phosphate increases the expression of Dentin matrix acidic phosphoprotein 1 (DMP1). [38]
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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 Dentin matrix acidic phosphoprotein 1 (DMP1). [39]
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References

1 Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006 Nov;38(11):1310-5. doi: 10.1038/ng1905. Epub 2006 Oct 8.
2 Dentin matrix protein 1 is expressed in human lung cancer.J Bone Miner Res. 2003 Aug;18(8):1506-12. doi: 10.1359/jbmr.2003.18.8.1506.
3 Osteogenic Dkk1 Mediates Glucocorticoid-Induced but Not Arthritis-Induced Bone Loss.J Bone Miner Res. 2019 Jul;34(7):1314-1323. doi: 10.1002/jbmr.3702. Epub 2019 Mar 7.
4 Hypophosphatemic osteosclerosis, hyperostosis, and enthesopathy associated with novel homozygous mutations of DMP1 encoding dentin matrix protein 1 and SPP1 encoding osteopontin: The first digenic SIBLING protein osteopathy?.Bone. 2020 Mar;132:115190. doi: 10.1016/j.bone.2019.115190. Epub 2019 Dec 13.
5 DMP1, a splice isoform of the tumour suppressor DMP1 locus, induces proliferation and progression of breast cancer.J Pathol. 2015 May;236(1):90-102. doi: 10.1002/path.4504. Epub 2015 Feb 9.
6 Low dentin matrix protein 1 expression correlates with skeletal metastases development in breast cancer patients and enhances cell migratory capacity in vitro.Breast Cancer Res Treat. 2007 Sep;105(1):95-104. doi: 10.1007/s10549-006-9436-0. Epub 2006 Nov 30.
7 Dentin matrix protein 1 enhances invasion potential of colon cancer cells by bridging matrix metalloproteinase-9 to integrins and CD44.Cancer Res. 2005 Dec 15;65(24):11545-52. doi: 10.1158/0008-5472.CAN-05-2861.
8 DMP-1 attenuates oxidative stress and inhibits TGF- activation in rats with diabetic kidney disease.Ren Fail. 2017 Nov;39(1):229-235. doi: 10.1080/0886022X.2016.1256319. Epub 2016 Nov 23.
9 Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers.Clin Cancer Res. 2004 Dec 15;10(24):8501-11. doi: 10.1158/1078-0432.CCR-04-1072.
10 Dentin matrix protein 1 correlates with the severity of hemorrhagic fever with renal syndrome and promotes hyper-permeability of endothelial cells infected by Hantaan virus.Microbes Infect. 2019 Aug-Sep;21(7):321-327. doi: 10.1016/j.micinf.2019.01.003. Epub 2019 Feb 5.
11 The Role of Dickkopf-1 in Thyroid Hormone-Induced Changes of Bone Remodeling in Male Mice.Endocrinology. 2019 Mar 1;160(3):664-674. doi: 10.1210/en.2018-00998.
12 Unique roles of phosphorus in endochondral bone formation and osteocyte maturation.J Bone Miner Res. 2011 May;26(5):1047-56. doi: 10.1002/jbmr.294.
13 Role of DMP1 and its future in lung cancer diagnostics.Expert Rev Mol Diagn. 2008 Jul;8(4):435-47. doi: 10.1586/14737159.8.4.435.
14 Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.Mod Pathol. 2004 May;17(5):573-8. doi: 10.1038/modpathol.3800084.
15 Bone and heart health in chronic kidney disease: role of dentin matrix protein 1.Curr Opin Nephrol Hypertens. 2019 Jul;28(4):297-303. doi: 10.1097/MNH.0000000000000512.
16 Understanding Decision Making about Breast Cancer Prevention in Action: The Intersection of Perceived Risk, Perceived Control, and Social Context: NRG Oncology/NSABP DMP-1.Med Decis Making. 2019 Apr;39(3):217-227. doi: 10.1177/0272989X19827258. Epub 2019 Feb 25.
17 Osteocytes serve as a progenitor cell of osteosarcoma.J Cell Biochem. 2014 Aug;115(8):1420-9. doi: 10.1002/jcb.24793.
18 Glycosylation of DMP1 Is Essential for Chondrogenesis of Condylar Cartilage.J Dent Res. 2017 Dec;96(13):1535-1545. doi: 10.1177/0022034517717485. Epub 2017 Jul 31.
19 Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.J Bone Miner Res. 2010 Oct;25(10):2165-74. doi: 10.1002/jbmr.105.
20 BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.J Dent Res. 2017 May;96(5):578-585. doi: 10.1177/0022034516686558. Epub 2017 Jan 9.
21 Attenuated Dentin Matrix Protein 1 Enhances Fibroblast Growth Factor 23 in Calvaria in a Primary Hyperparathyroidism Model.Endocrinology. 2019 May 1;160(5):1348-1358. doi: 10.1210/en.2019-00017.
22 The rachitic tooth.Endocr Rev. 2014 Feb;35(1):1-34. doi: 10.1210/er.2013-1009. Epub 2013 Dec 4.
23 Genome-wide identification of chromatin-enriched RNA reveals that unspliced dentin matrix protein-1 mRNA regulates cell proliferation in squamous cell carcinoma.Biochem Biophys Res Commun. 2018 Jan 15;495(3):2303-2309. doi: 10.1016/j.bbrc.2017.12.136. Epub 2017 Dec 24.
24 Hypophosphatemic rickets accelerate chondrogenesis and cell trans-differentiation from TMJ chondrocytes into bone cells via a sharp increase in -catenin.Bone. 2020 Feb;131:115151. doi: 10.1016/j.bone.2019.115151. Epub 2019 Nov 18.
25 Aberrant splicing of the DMP1-ARF-MDM2-p53 pathway in cancer.Int J Cancer. 2016 Jul 1;139(1):33-41. doi: 10.1002/ijc.30003. Epub 2016 Feb 8.
26 Cooperation between Dmp1 loss and cyclin D1 overexpression in breast cancer.Am J Pathol. 2013 Oct;183(4):1339-1350. doi: 10.1016/j.ajpath.2013.06.027. Epub 2013 Aug 11.
27 Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer.Cancer Cell. 2007 Oct;12(4):381-94. doi: 10.1016/j.ccr.2007.08.034.
28 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
29 Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats.J Mol Histol. 2017 Apr;48(2):73-81. doi: 10.1007/s10735-016-9707-y. Epub 2016 Dec 15.
30 Human DMTF1 antagonizes DMTF1 regulation of the p14(ARF) tumor suppressor and promotes cellular proliferation.Biochim Biophys Acta. 2015 Sep;1849(9):1198-208. doi: 10.1016/j.bbagrm.2015.07.009. Epub 2015 Jul 15.
31 Association Between Dentin Matrix Protein 1 (rs10019009) Polymorphism and Ankylosing Spondylitis in a Chinese Han Population from Shandong Province.Chin Med J (Engl). 2016 Mar 20;129(6):657-64. doi: 10.4103/0366-6999.177972.
32 Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD.JCI Insight. 2019 Feb 21;4(4):e123817. doi: 10.1172/jci.insight.123817. eCollection 2019 Feb 21.
33 Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries.Biochim Biophys Acta. 2005 Sep 25;1741(3):271-81. doi: 10.1016/j.bbadis.2005.03.007. Epub 2005 Apr 8.
34 Effect of Osteocyte-Ablation on Inorganic Phosphate Metabolism: Analysis of Bone-Kidney-Gut Axis.Front Endocrinol (Lausanne). 2017 Dec 21;8:359. doi: 10.3389/fendo.2017.00359. eCollection 2017.
35 Osteolytic prostate cancer cells induce the expression of specific cytokines in bone-forming osteoblasts through a Stat3/5-dependent mechanism.Bone. 2010 Feb;46(2):524-33. doi: 10.1016/j.bone.2009.09.024. Epub 2009 Sep 29.
36 Disruption of the ARF transcriptional activator DMP1 facilitates cell immortalization, Ras transformation, and tumorigenesis.Genes Dev. 2000 Jul 15;14(14):1797-809.
37 Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell. J Dent. 2021 Jun;109:103673. doi: 10.1016/j.jdent.2021.103673. Epub 2021 Apr 16.
38 Inorganic phosphate stimulates DMP1 expression in human periodontal ligament fibroblasts embedded in three-dimensional collagen gels. Cells Tissues Organs. 2010;192(2):116-24. doi: 10.1159/000289585. Epub 2010 Feb 24.
39 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.