Details of Drug Off-Target (DOT)

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

DOT Name Lysine-specific demethylase hairless (HR)
Synonyms EC 1.14.11.65; -dimethyl-L-lysine(9) demethylase hairless
Gene Name HR
Related Disease
Atrichia with papular lesions ( )
Hypotrichosis 4 ( )
Congenital alopecia ( )
Androgenetic alopecia ( )
Baldness, male pattern ( )
Alopecia universalis congenita ( )
Marie Unna hereditary hypotrichosis ( )
Alopecia ( )
UniProt ID
HAIR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
1.14.11.65
Pfam ID
PF02373
Sequence
MESTPSFLKGTPTWEKTAPENGIVRQEPGSPPRDGLHHGPLCLGEPAPFWRGVLSTPDSW
LPPGFPQGPKDMLPLVEGEGPQNGERKVNWLGSKEGLRWKEAMLTHPLAFCGPACPPRCG
PLMPEHSGGHLKSDPVAFRPWHCPFLLETKILERAPFWVPTCLPPYLVSGLPPEHPCDWP
LTPHPWVYSGGQPKVPSAFSLGSKGFYYKDPSIPRLAKEPLAAAEPGLFGLNSGGHLQRA
GEAERPSLHQRDGEMGAGRQQNPCPLFLGQPDTVPWTSWPACPPGLVHTLGNVWAGPGDG
NLGYQLGPPATPRCPSPEPPVTQRGCCSSYPPTKGGGLGPCGKCQEGLEGGASGASEPSE
EVNKASGPRACPPSHHTKLKKTWLTRHSEQFECPRGCPEVEERPVARLRALKRAGSPEVQ
GAMGSPAPKRPPDPFPGTAEQGAGGWQEVRDTSIGNKDVDSGQHDEQKGPQDGQASLQDP
GLQDIPCLALPAKLAQCQSCAQAAGEGGGHACHSQQVRRSPLGGELQQEEDTATNSSSEE
GPGSGPDSRLSTGLAKHLLSGLGDRLCRLLRREREALAWAQREGQGPAVTEDSPGIPRCC
SRCHHGLFNTHWRCPRCSHRLCVACGRVAGTGRAREKAGFQEQSAEECTQEAGHAACSLM
LTQFVSSQALAELSTAMHQVWVKFDIRGHCPCQADARVWAPGDAGQQKESTQKTPPTPQP
SCNGDTHRTKSIKEETPDSAETPAEDRAGRGPLPCPSLCELLASTAVKLCLGHERIHMAF
APVTPALPSDDRITNILDSIIAQVVERKIQEKALGPGLRAGPGLRKGLGLPLSPVRPRLP
PPGALLWLQEPQPCPRRGFHLFQEHWRQGQPVLVSGIQRTLQGNLWGTEALGALGGQVQA
LSPLGPPQPSSLGSTTFWEGFSWPELRPKSDEGSVLLLHRALGDEDTSRVENLAASLPLP
EYCALHGKLNLASYLPPGLALRPLEPQLWAAYGVSPHRGHLGTKNLCVEVADLVSILVHA
DTPLPAWHRAQKDFLSGLDGEGLWSPGSQVSTVWHVFRAQDAQRIRRFLQMVCPAGAGAL
EPGAPGSCYLDAGLRRRLREEWGVSCWTLLQAPGEAVLVPAGAPHQVQGLVSTVSVTQHF
LSPETSALSAQLCHQGPSLPPDCHLLYAQMDWAVFQAVKVAVGTLQEAK
Function
Histone demethylase that specifically demethylates both mono- and dimethylated 'Lys-9' of histone H3. May act as a transcription regulator controlling hair biology (via targeting of collagens), neural activity, and cell cycle.
Tissue Specificity
Strongest expression of isoforms 1 and 2 is seen in the small intestine, weaker expression in brain and colon, and trace expression is found in liver, pancreas, spleen, thymus, stomach, salivary gland, appendix and trachea. Isoform 1 is always the most abundant. Isoform 1 is exclusively expressed at low levels in kidney and testis. Isoform 2 is exclusively expressed at high levels in the skin.
BioCyc Pathway
MetaCyc:ENSG00000168453-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Atrichia with papular lesions DIS80CUB Definitive Autosomal recessive [1]
Hypotrichosis 4 DISGUZJ4 Definitive Autosomal recessive [2]
Congenital alopecia DIS1LDG6 Strong Genetic Variation [3]
Androgenetic alopecia DISSJR1P moderate Biomarker [4]
Baldness, male pattern DIS9C9RO moderate Biomarker [4]
Alopecia universalis congenita DIS57F9M Supportive Autosomal recessive [1]
Marie Unna hereditary hypotrichosis DISYE5SW Supportive Autosomal dominant [5]
Alopecia DIS37HU4 Limited Genetic Variation [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Lysine-specific demethylase hairless (HR). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Lysine-specific demethylase hairless (HR). [18]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Lysine-specific demethylase hairless (HR). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Lysine-specific demethylase hairless (HR). [22]
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16 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 Lysine-specific demethylase hairless (HR). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Lysine-specific demethylase hairless (HR). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Lysine-specific demethylase hairless (HR). [10]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Lysine-specific demethylase hairless (HR). [11]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Lysine-specific demethylase hairless (HR). [12]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Lysine-specific demethylase hairless (HR). [13]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Lysine-specific demethylase hairless (HR). [14]
Liothyronine DM6IR3P Approved Liothyronine increases the expression of Lysine-specific demethylase hairless (HR). [15]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Lysine-specific demethylase hairless (HR). [16]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Lysine-specific demethylase hairless (HR). [17]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Lysine-specific demethylase hairless (HR). [12]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Lysine-specific demethylase hairless (HR). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Lysine-specific demethylase hairless (HR). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Lysine-specific demethylase hairless (HR). [23]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Lysine-specific demethylase hairless (HR). [24]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Lysine-specific demethylase hairless (HR). [25]
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⏷ Show the Full List of 16 Drug(s)

References

1 Alopecia universalis associated with a mutation in the human hairless gene. Science. 1998 Jan 30;279(5351):720-4. doi: 10.1126/science.279.5351.720.
2 Overexpression of Hr links excessive induction of Wnt signaling to Marie Unna hereditary hypotrichosis. Hum Mol Genet. 2010 Feb 1;19(3):445-53. doi: 10.1093/hmg/ddp509. Epub 2009 Nov 6.
3 A gene for universal congenital alopecia maps to chromosome 8p21-22.Am J Hum Genet. 1998 Feb;62(2):386-90. doi: 10.1086/301717.
4 A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu.Genomics. 2006 Apr;87(4):520-6. doi: 10.1016/j.ygeno.2005.12.005. Epub 2006 Feb 7.
5 Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. Nat Genet. 2009 Feb;41(2):228-33. doi: 10.1038/ng.276. Epub 2009 Jan 4.
6 A newly identified missense mutation of the HR gene is associated with a novel, unusual phenotype of Marie Unna Hereditary Hypotrichosis 1 including limb deformities.Arch Dermatol Res. 2012 Oct;304(8):679-81. doi: 10.1007/s00403-012-1244-2. Epub 2012 May 15.
7 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
8 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
9 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
10 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
11 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
12 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
13 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
14 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
15 Pituitary specific retinoid-X receptor ligand interactions with thyroid hormone receptor signaling revealed by high throughput reporter and endogenous gene responses. Toxicol In Vitro. 2015 Oct;29(7):1609-18. doi: 10.1016/j.tiv.2015.06.018. Epub 2015 Jun 19.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
18 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.
19 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
20 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
21 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
22 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
23 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
24 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
25 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.