Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2LRTG4)

DOT Name Ribosomal protein S6 kinase delta-1 (RPS6KC1)
Synonyms S6K-delta-1; EC 2.7.11.1; 52 kDa ribosomal protein S6 kinase; Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein; SPHK1-binding protein
Gene Name RPS6KC1
Related Disease
Periventricular leukomalacia ( )
UniProt ID
KS6C1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.1
Pfam ID
PF04212 ; PF00069 ; PF00787
Sequence
MTSYRERSADLARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKL
HKELWQIHKNLFRHSELFPPFAKGIVFGRFDETVIEERRQCAEDLLQFSANIPALYNSKQ
LEDFFKGGIINDSSELIGPAEAHSDSLIDTFPECSTEGFSSDSDLVSLTVDVDSLAELDD
GMASNQNSPIRTFGLNLSSDSSALGAVASDSEQSKTEEERESRSLFPGSLKPKLGKRDYL
EKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRA
ESISSLYGKPQLDDVSQPPGSLSSRPLWNLRSPAEELKAFRVLGVIDKVLLVMDTRTEQT
FILKGLRKSSEYSRNRKTIIPRCVPNMVCLHKYIISEESVFLVLQHAEGGKLWSYISKFL
NRSPEESFDIKEVKKPTLAKVHLQQPTSSPQDSSSFESRGSDGGSMLKALPLKSSLTPSS
QDDSNQEDDGQDSSPKWPDSGSSSEEECTTSYLTLCNEYGQEKIEPGSLNEEPFMKTEGN
GVDTKAIKSFPAHLAADSDSPSTQLRAHELKFFPNDDPEAVSSPRTSDSLSRSKNSPMEF
FRIDSKDSASELLGLDFGEKLYSLKSEPLKPFFTLPDGDSASRSFNTSESKVEFKAQDTI
SRGSDDSVPVISFKDAAFDDVSGTDEGRPDLLVNLPGELESTREAAAMGPTKFTQTNIGI
IENKLLEAPDVLCLRLSTEQCQAHEEKGIEELSDPSGPKSYSITEKHYAQEDPRMLFVAA
VDHSSSGDMSLLPSSDPKFQGLGVVESAVTANNTEESLFRICSPLSGANEYIASTDTLKT
EEVLLFTDQTDDLAKEEPTSLFQRDSETKGESGLVLEGDKEIHQIFEDLDKKLALASRFY
IPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEVEDSCDS
DAIERMYCAPEVGAITEETEACDWWSLGAVLFELLTGKTLVECHPAGINTHTTLNMPECV
SEEARSLIQQLLQFNPLERLGAGVAGVEDIKSHPFFTPVDWAELMR
Function May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell. Plays a role in the recruitment of PRDX3 to early endosomes.
Tissue Specificity Highly expressed in testis, skeletal muscle, brain, heart, placenta, kidney and liver and weakly expressed in thymus, small intestine, lung and colon.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Periventricular leukomalacia DIS152XL Limited Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Ribosomal protein S6 kinase delta-1 (RPS6KC1). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [5]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [8]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [10]
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⏷ Show the Full List of 8 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [9]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Ribosomal protein S6 kinase delta-1 (RPS6KC1). [9]
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References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 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.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
5 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.
6 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
7 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
8 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.
9 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
10 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.