Details of Drug Off-Target (DOT)

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

DOT Name E3 ubiquitin-protein ligase SHPRH (SHPRH)
Synonyms EC 2.3.2.27; EC 3.6.4.-; RING-type E3 ubiquitin transferase SHPRH; SNF2, histone-linker, PHD and RING finger domain-containing helicase
Gene Name SHPRH
Related Disease
Hepatocellular carcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Neoplasm ( )
UniProt ID
SHPRH_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2M85; 4QN1
EC Number
2.3.2.27; 3.6.4.-
Pfam ID
PF00271 ; PF00538 ; PF21325 ; PF21324 ; PF00176 ; PF13445
Sequence
MSSRRKRAPPVRVDEEKRQQLHWNMHEDRRNEPIIISDDDEQPCPGSDTSSAHYIILSDS
LKEEVAHRDKKRCSKVVSFSKPIEKEETVGIFSPLSVKLNIVISPYHFDNSWKAFLGELT
LQLLPAQSLIENFSERSITLMSSESSNQFLIYVHSKGEDVEKQKKEPMSICDKGILVESS
FSGEMLEDLGWLQKKRRIKLYQKPEGNHIIKVGIYLLEAGLAKLDFLSDANSRMKKFNQL
MKKVMEKLHNSIIPDVLEEDEDDPESEPEGQDIDELYHFVKQTHQQETQSIQVDVQHPAL
IPVLRPYQREAVNWMLQQECFRSSPATESALHFLWREIVTSEGLKLYYNPYTGCIIREYP
NSGPQLLGGILADEMGLGKTVEVLALILTHTRQDVKQDALTLPEGKVVNYFIPSHYFGGK
LKKTEIQNIEFEPKEKVQCPPTRVMILTAVKEMNGKKGVSILSIYKYVSSIYRYDVQRNR
SLLKRMLKCLIFEGLVKQIKGHGFSGTFTLGKNYKEEDICDKTKKQAVGSPRKIQKETRK
SGNKDTDSEYLPSDTSDDDDDPYYYYYKSRRNRSKLRKKLVPSTKKGKSQPFINPDSQGH
CPATSDSGITDVAMSKSTCISEFNQEHETEDCAESLNHADSDVPPSNTMSPFNTSDYRFE
CICGELDQIDRKPRVQCLKCHLWQHAKCVNYDEKNLKIKPFYCPHCLVAMEPVSTRATLI
ISPSSICHQWVDEINRHVRSSSLRVLVYQGVKKDGFLQPHFLAEQDIVIITYDVLRSELN
YVDIPHSNSEDGRRLRNQKRYMAIPSPLVAVEWWRICLDEAQMVECPTVKAAEMAQRLSG
INRWCISGTPVQRGLEDLFGLVVFLGIEPYCVKHWWVRLLYRPYCKKNPQHLYSFIAKIL
WRSAKKDVIDQIQIPPQTEEIHWLHFSPVERHFYHRQHEVCCQDVVVKLRKISDWALKLS
SLDRRTVTSILYPLLRLRQACCHPQAVRGEFLPLQKSTMTMEELLTSLQKKCGTECEEAH
RQLVCALNGLAGIHIIKGEYALAAELYREVLRSSEEHKGKLKTDSLQRLHATHNLMELLI
ARHPGIPPTLRDGRLEEEAKQLREHYMSKCNTEVAEAQQALYPVQQTIHELQRKIHSNSP
WWLNVIHRAIEFTIDEELVQRVRNEITSNYKQQTGKLSMSEKFRDCRGLQFLLTTQMEEL
NKCQKLVREAVKNLEGPPSRNVIESATVCHLRPARLPLNCCVFCKADELFTEYESKLFSN
TVKGQTAIFEEMIEDEEGLVDDRAPTTTRGLWAISETERSMKAILSFAKSHRFDVEFVDE
GSTSMDLFEAWKKEYKLLHEYWMALRNRVSAVDELAMATERLRVRDPREPKPNPPVLHII
EPHEVEQNRIKLLNDKAVATSQLQKKLGQLLYLTNLEKSQDKTSGGVNPEPCPICARQLG
KQWAVLTCGHCFCNECISIIIEQYSVGSHRSSIKCAICRQTTSHKEISYVFTSEKANQEE
DIPVKGSHSTKVEAVVRTLMKIQLRDPGAKALVFSTWQDVLDIISKALTDNNMEFAQISR
VKTFQENLSAFKRDPQINILLLPLHTGSNGLTIIEATHVLLVEPILNPAHELQAIGRVHR
IGQTKPTIVHRFLIKATIEERMQAMLKTAERSHTNSSAKHSEASVLTVADLADLFTKETE
ELE
Function
E3 ubiquitin-protein ligase involved in DNA repair. Upon genotoxic stress, accepts ubiquitin from the UBE2N-UBE2V2 E2 complex and transfers it to 'Lys-164' of PCNA which had been monoubiquitinated by UBE2A/B-RAD18, promoting the formation of non-canonical poly-ubiquitin chains linked through 'Lys-63'.
Tissue Specificity Broadly expressed.
Reactome Pathway
E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Definitive Biomarker [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Glioblastoma multiforme DISK8246 Strong Altered Expression [2]
Glioma DIS5RPEH Strong Genetic Variation [4]
Neoplasm DISZKGEW Strong Biomarker [4]
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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
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of E3 ubiquitin-protein ligase SHPRH (SHPRH). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of E3 ubiquitin-protein ligase SHPRH (SHPRH). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase SHPRH (SHPRH). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of E3 ubiquitin-protein ligase SHPRH (SHPRH). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of E3 ubiquitin-protein ligase SHPRH (SHPRH). [9]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of E3 ubiquitin-protein ligase SHPRH (SHPRH). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of E3 ubiquitin-protein ligase SHPRH (SHPRH). [11]
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References

1 Circular RNA hsa_circ_0001649 inhibits hepatocellular carcinoma progression via multiple miRNAs sponge.Aging (Albany NY). 2019 May 28;11(10):3362-3375. doi: 10.18632/aging.101988.
2 Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas.Oncogene. 2018 Jul;37(30):4055-4057. doi: 10.1038/s41388-018-0230-3. Epub 2018 Apr 30.
3 SNF2 histone linker PHD RING helicase related Has_circ_0001649 as a diagnostic and prognostic biomarker in solid cancer: A PRISMA-compliant meta-analysis based on the Chinese population.Medicine (Baltimore). 2019 Nov;98(44):e17488. doi: 10.1097/MD.0000000000017488.
4 A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis.Oncogene. 2018 Mar;37(13):1805-1814. doi: 10.1038/s41388-017-0019-9. Epub 2018 Jan 18.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
10 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.
11 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.