Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT083IH0)

DOT Name Rhodopsin kinase GRK7 (GRK7)
Synonyms EC 2.7.11.14; G protein-coupled receptor kinase 7; G protein-coupled receptor kinase GRK7
Gene Name GRK7
Related Disease
Congenital stationary night blindness ( )
Enhanced S-cone syndrome ( )
Leber congenital amaurosis 12 ( )
Melanoma ( )
Oguchi disease ( )
Retinitis pigmentosa ( )
UniProt ID
GRK7_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.14
Pfam ID
PF00069 ; PF00615
Sequence
MVDMGALDNLIANTAYLQARKPSDCDSKELQRRRRSLALPGLQGCAELRQKLSLNFHSLC
EQQPIGRRLFRDFLATVPTFRKAATFLEDVQNWELAEEGPTKDSALQGLVATCASAPAPG
NPQPFLSQAVATKCQAATTEEERVAAVTLAKAEAMAFLQEQPFKDFVTSAFYDKFLQWKL
FEMQPVSDKYFTEFRVLGKGGFGEVCAVQVKNTGKMYACKKLDKKRLKKKGGEKMALLEK
EILEKVSSPFIVSLAYAFESKTHLCLVMSLMNGGDLKFHIYNVGTRGLDMSRVIFYSAQI
ACGMLHLHELGIVYRDMKPENVLLDDLGNCRLSDLGLAVEMKGGKPITQRAGTNGYMAPE
ILMEKVSYSYPVDWFAMGCSIYEMVAGRTPFKDYKEKVSKEDLKQRTLQDEVKFQHDNFT
EEAKDICRLFLAKKPEQRLGSREKSDDPRKHHFFKTINFPRLEAGLIEPPFVPDPSVVYA
KDIAEIDDFSEVRGVEFDDKDKQFFKNFATGAVPIAWQEEIIETGLFEELNDPNRPTGCE
EGNSSKSGVCLLL
Function Retina-specific kinase involved in the shutoff of the photoresponse and adaptation to changing light conditions via cone opsin phosphorylation, including rhodopsin (RHO).
Tissue Specificity Retinal cones, outer and inner segments.
KEGG Pathway
Chemokine sig.ling pathway (hsa04062 )
Endocytosis (hsa04144 )
Phototransduction (hsa04744 )
Reactome Pathway
Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Congenital stationary night blindness DISX0CWK Strong Genetic Variation [1]
Enhanced S-cone syndrome DIS2IWS3 Strong Biomarker [2]
Leber congenital amaurosis 12 DIS0EIZY Strong Genetic Variation [3]
Melanoma DIS1RRCY Strong Altered Expression [4]
Oguchi disease DISLYKY5 Strong Genetic Variation [5]
Retinitis pigmentosa DISCGPY8 Strong Genetic Variation [6]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Rhodopsin kinase GRK7 (GRK7). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Rhodopsin kinase GRK7 (GRK7). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rhodopsin kinase GRK7 (GRK7). [9]
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References

1 Biochemical evidence for pathogenicity of rhodopsin kinase mutations correlated with the oguchi form of congenital stationary night blindness.Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2824-7. doi: 10.1073/pnas.95.6.2824.
2 Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3.Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1268-74. doi: 10.1167/iovs.02-0494.
3 RD3 gene delivery restores guanylate cyclase localization and rescues photoreceptors in the Rd3 mouse model of Leber congenital amaurosis 12.Hum Mol Genet. 2013 Oct 1;22(19):3894-905. doi: 10.1093/hmg/ddt244. Epub 2013 Jun 4.
4 Photoreceptor proteins as cancer-retina antigens.Int J Cancer. 2007 Mar 15;120(6):1268-76. doi: 10.1002/ijc.22458.
5 A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses. Ophthalmology. 2007 Jan;114(1):134-41. doi: 10.1016/j.ophtha.2006.05.069. Epub 2006 Oct 27.
6 Evaluation of the rhodopsin kinase gene in patients with retinitis pigmentosa.Exp Eye Res. 1997 Aug;65(2):249-53. doi: 10.1006/exer.1997.9998.
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 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.
9 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.