Details of Drug Off-Target (DOT)

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

DOT Name L-dopachrome tautomerase (DCT)
Synonyms DCT; DT; EC 5.3.3.12; L-dopachrome Delta-isomerase; Tyrosinase-related protein 2; TRP-2; TRP2
Gene Name DCT
Related Disease
Microphthalmia ( )
Advanced cancer ( )
Albinism ( )
Autoimmune disease ( )
Chromosomal disorder ( )
Classic Hodgkin lymphoma ( )
Cystic fibrosis ( )
Early-onset posterior polar cataract ( )
Glioma ( )
Graves disease ( )
Huntington disease ( )
Hypopigmentation of the skin ( )
Malignant glioma ( )
Meningioma ( )
Neoplasm ( )
Oculocutaneous albinism type 8 ( )
Primary sclerosing cholangitis ( )
Retinoblastoma ( )
Sciatica/lumbar radicular pain ( )
Skin pigmentation disorder ( )
Trichorhinophalangeal syndrome type II ( )
Vitiligo ( )
Bartter syndrome ( )
Frontotemporal dementia ( )
Nephrocalcinosis ( )
Pick disease ( )
Retinopathy ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Dowling-Degos disease ( )
Human papillomavirus infection ( )
Thyroid gland papillary carcinoma ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
UniProt ID
TYRP2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4HX1
EC Number
5.3.3.12
Pfam ID
PF00264
Sequence
MSPLWWGFLLSCLGCKILPGAQGQFPRVCMTVDSLVNKECCPRLGAESANVCGSQQGRGQ
CTEVRADTRPWSGPYILRNQDDRELWPRKFFHRTCKCTGNFAGYNCGDCKFGWTGPNCER
KKPPVIRQNIHSLSPQEREQFLGALDLAKKRVHPDYVITTQHWLGLLGPNGTQPQFANCS
VYDFFVWLHYYSVRDTLLGPGRPYRAIDFSHQGPAFVTWHRYHLLCLERDLQRLIGNESF
ALPYWNFATGRNECDVCTDQLFGAARPDDPTLISRNSRFSSWETVCDSLDDYNHLVTLCN
GTYEGLLRRNQMGRNSMKLPTLKDIRDCLSLQKFDNPPFFQNSTFSFRNALEGFDKADGT
LDSQVMSLHNLVHSFLNGTNALPHSAANDPIFVVLHSFTDAIFDEWMKRFNPPADAWPQE
LAPIGHNRMYNMVPFFPPVTNEELFLTSDQLGYSYAIDLPVSVEETPGWPTTLLVVMGTL
VALVGLFVLLAFLQYRRLRKGYTPLMETHLSSKRYTEEA
Function Plays a role in melanin biosynthesis. Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA).
KEGG Pathway
Tyrosine metabolism (hsa00350 )
Metabolic pathways (hsa01100 )
Melanogenesis (hsa04916 )
Reactome Pathway
Melanin biosynthesis (R-HSA-5662702 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Microphthalmia DISGEBES Definitive Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Albinism DIS5D82I Strong Genetic Variation [3]
Autoimmune disease DISORMTM Strong Biomarker [4]
Chromosomal disorder DISM5BB5 Strong Biomarker [5]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [6]
Cystic fibrosis DIS2OK1Q Strong Biomarker [7]
Early-onset posterior polar cataract DISJFK9W Strong Biomarker [8]
Glioma DIS5RPEH Strong Altered Expression [9]
Graves disease DISU4KOQ Strong Biomarker [4]
Huntington disease DISQPLA4 Strong Biomarker [6]
Hypopigmentation of the skin DIS39YKC Strong Biomarker [10]
Malignant glioma DISFXKOV Strong Biomarker [11]
Meningioma DISPT4TG Strong Altered Expression [9]
Neoplasm DISZKGEW Strong Biomarker [12]
Oculocutaneous albinism type 8 DISOFZK2 Strong Autosomal recessive [13]
Primary sclerosing cholangitis DISTH5WJ Strong Biomarker [8]
Retinoblastoma DISVPNPB Strong Altered Expression [14]
Sciatica/lumbar radicular pain DIS01KTQ Strong Genetic Variation [15]
Skin pigmentation disorder DIS3BXY0 Strong Biomarker [16]
Trichorhinophalangeal syndrome type II DISW4YZ1 Strong Biomarker [17]
Vitiligo DISR05SL Strong Biomarker [18]
Bartter syndrome DIS7D44B moderate Biomarker [19]
Frontotemporal dementia DISKYHXL moderate Genetic Variation [20]
Nephrocalcinosis DIS5ZVJP moderate Biomarker [19]
Pick disease DISP6X50 moderate Genetic Variation [20]
Retinopathy DISB4B0F moderate Biomarker [21]
Adult glioblastoma DISVP4LU Disputed Biomarker [22]
Glioblastoma multiforme DISK8246 Disputed Biomarker [22]
Dowling-Degos disease DISGTTEP Limited Biomarker [23]
Human papillomavirus infection DISX61LX Limited Biomarker [24]
Thyroid gland papillary carcinoma DIS48YMM Limited Genetic Variation [25]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Limited Biomarker [25]
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⏷ Show the Full List of 33 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 4 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved L-dopachrome tautomerase (DCT) decreases the response to substance of Temozolomide. [39]
Etoposide DMNH3PG Approved L-dopachrome tautomerase (DCT) affects the response to substance of Etoposide. [40]
Mitomycin DMH0ZJE Approved L-dopachrome tautomerase (DCT) affects the response to substance of Mitomycin. [40]
Deoxycholic acid DM3GYAL Approved L-dopachrome tautomerase (DCT) increases the Cell death ADR of Deoxycholic acid. [41]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of L-dopachrome tautomerase (DCT). [26]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of L-dopachrome tautomerase (DCT). [27]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of L-dopachrome tautomerase (DCT). [28]
Fluorouracil DMUM7HZ Approved Fluorouracil affects the expression of L-dopachrome tautomerase (DCT). [28]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of L-dopachrome tautomerase (DCT). [29]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of L-dopachrome tautomerase (DCT). [30]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of L-dopachrome tautomerase (DCT). [31]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate decreases the expression of L-dopachrome tautomerase (DCT). [32]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the expression of L-dopachrome tautomerase (DCT). [34]
EMODIN DMAEDQG Terminated EMODIN decreases the expression of L-dopachrome tautomerase (DCT). [35]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of L-dopachrome tautomerase (DCT). [36]
Forskolin DM6ITNG Investigative Forskolin increases the expression of L-dopachrome tautomerase (DCT). [29]
AMENTOFLAVONE DMLRNV2 Investigative AMENTOFLAVONE decreases the expression of L-dopachrome tautomerase (DCT). [37]
CyPPA DM64L9I Investigative CyPPA decreases the expression of L-dopachrome tautomerase (DCT). [38]
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⏷ Show the Full List of 14 Drug(s)
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 decreases the methylation of L-dopachrome tautomerase (DCT). [33]
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References

1 Knockdown of microRNA?43?p by STTM technology affects eumelanin and pheomelanin production in melanocytes.Mol Med Rep. 2019 Sep;20(3):2649-2656. doi: 10.3892/mmr.2019.10492. Epub 2019 Jul 12.
2 Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy.Biomaterials. 2018 Aug;174:54-66. doi: 10.1016/j.biomaterials.2018.05.015. Epub 2018 May 10.
3 White mutants in mice shedding light on humans.J Invest Dermatol. 1993 Feb;100(2 Suppl):176S-185S.
4 Immunoprecipitation of melanogenic enzyme autoantigens with vitiligo sera: evidence for cross-reactive autoantibodies to tyrosinase and tyrosinase-related protein-2 (TRP-2).Clin Exp Immunol. 1997 Sep;109(3):495-500. doi: 10.1046/j.1365-2249.1997.4781381.x.
5 Chromosome deletion and multiple cartilaginous exostoses.Eur J Pediatr. 1980 Mar;133(2):163-6. doi: 10.1007/BF00441586.
6 Dietary Tryptophan Induces Opposite Health-Related Responses in the Senegalese Sole (Solea senegalensis) Reared at Low or High Stocking Densities With Implications in Disease Resistance.Front Physiol. 2019 May 1;10:508. doi: 10.3389/fphys.2019.00508. eCollection 2019.
7 Initial clinical evaluation of stationary digital chest tomosynthesis in adult patients with cystic fibrosis.Eur Radiol. 2019 Apr;29(4):1665-1673. doi: 10.1007/s00330-018-5703-9. Epub 2018 Sep 25.
8 Development and characterization of naive single-type tumor antigen-specific CD8(+) T lymphocytes from murine pluripotent stem cells.Oncoimmunology. 2017 May 30;6(7):e1334027. doi: 10.1080/2162402X.2017.1334027. eCollection 2017.
9 Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma.J Clin Neurosci. 2012 Jul;19(7):1016-21. doi: 10.1016/j.jocn.2011.10.008. Epub 2012 Apr 23.
10 Biolistic DNA vaccination against melanoma.Methods Mol Biol. 2013;940:317-37. doi: 10.1007/978-1-62703-110-3_24.
11 Molecular and functional analysis of tyrosinase-related protein (TRP)-2 as a cytotoxic T lymphocyte target in patients with malignant glioma.J Immunother. 2003 Jul-Aug;26(4):301-12. doi: 10.1097/00002371-200307000-00002.
12 Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells.Oncoimmunology. 2018 Dec 5;8(3):1542917. doi: 10.1080/2162402X.2018.1542917. eCollection 2019.
13 Dopachrome tautomerase variants in patients with oculocutaneous albinism. Genet Med. 2021 Mar;23(3):479-487. doi: 10.1038/s41436-020-00997-8. Epub 2020 Oct 26.
14 Expression of tyrosinase-related protein 2/DOPAchrome tautomerase in the retinoblastoma.Exp Eye Res. 2001 Mar;72(3):225-34. doi: 10.1006/exer.2000.0948.
15 Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms.Eur Spine J. 2006 May;15(5):613-9. doi: 10.1007/s00586-005-0988-1. Epub 2005 Aug 17.
16 DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability.Exp Dermatol. 2014 Dec;23(12):916-21. doi: 10.1111/exd.12574.
17 A final word on the tricho-rhino-phalangeal syndromes.Clin Genet. 1987 Apr;31(4):273-5. doi: 10.1111/j.1399-0004.1987.tb02806.x.
18 Identification of pathogenic genes and transcription factors in vitiligo.Dermatol Ther. 2019 Sep;32(5):e13025. doi: 10.1111/dth.13025. Epub 2019 Aug 28.
19 Bartter's and Gitelman's syndrome.Curr Opin Pediatr. 2017 Apr;29(2):179-186. doi: 10.1097/MOP.0000000000000447.
20 Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation.Neurobiol Aging. 2019 Apr;76:214.e11-214.e15. doi: 10.1016/j.neurobiolaging.2018.11.010. Epub 2018 Nov 20.
21 Transcriptome analysis and molecular signature of human retinal pigment epithelium.Hum Mol Genet. 2010 Jun 15;19(12):2468-86. doi: 10.1093/hmg/ddq129. Epub 2010 Apr 1.
22 Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy.J Neurooncol. 2007 Jan;81(2):139-48. doi: 10.1007/s11060-006-9220-3. Epub 2006 Sep 27.
23 MRI Phenotyping of COL9A2/Trp2 and COL9A3/Trp3 Alleles in Lumbar Disc Disease: A Case-control Study in South-Western Iranian Population Reveals a Significant Trp3-Disease Association in Males.Spine (Phila Pa 1976). 2016 Nov 1;41(21):1661-1667. doi: 10.1097/BRS.0000000000001617.
24 The Role of DCT in HPV16 Infection of HaCaTs.PLoS One. 2017 Jan 17;12(1):e0170158. doi: 10.1371/journal.pone.0170158. eCollection 2017.
25 Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics.Front Endocrinol (Lausanne). 2017 Oct 20;8:277. doi: 10.3389/fendo.2017.00277. eCollection 2017.
26 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
27 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
28 Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Res. 2004 Jun 15;64(12):4218-26.
29 Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
30 Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J Invest Dermatol. 2007 Sep;127(9):2216-27. doi: 10.1038/sj.jid.5700840. Epub 2007 Apr 26.
31 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
32 Dynamic regulation of the human dopachrome tautomerase promoter by MITF, ER-alpha and chromatin remodelers during proliferation and senescence of human melanocytes. Pigment Cell Res. 2005 Jun;18(3):203-13. doi: 10.1111/j.1600-0749.2005.00229.x.
33 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.
34 Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells. Nutr Cancer. 2008;60(3):382-8.
35 Emodin isolated from Polygoni Multiflori Ramulus inhibits melanogenesis through the liver X receptor-mediated pathway. Chem Biol Interact. 2016 Apr 25;250:78-84. doi: 10.1016/j.cbi.2016.03.014. Epub 2016 Mar 10.
36 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
37 New constituent from Podocarpus macrophyllus var. macrophyllus shows anti-tyrosinase effect and regulates tyrosinase-related proteins and mRNA in human epidermal melanocytes. Chem Pharm Bull (Tokyo). 2007 May;55(5):757-61. doi: 10.1248/cpb.55.757.
38 The ion channel activator CyPPA inhibits melanogenesis via the GSK3/-catenin pathway. Chem Biol Interact. 2019 Feb 25;300:1-7. doi: 10.1016/j.cbi.2018.12.014. Epub 2018 Dec 28.
39 Cytotoxic T cell targeting of TRP-2 sensitizes human malignant glioma to chemotherapy. Oncogene. 2005 Aug 4;24(33):5226-34. doi: 10.1038/sj.onc.1208519.
40 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
41 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.