Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSZ3768)

DOT Name F-box only protein 38 (FBXO38)
Gene Name FBXO38
Related Disease
Autosomal recessive distal spinal muscular atrophy 2 ( )
Neoplasm ( )
Neuronopathy, distal hereditary motor, type 2D ( )
Distal hereditary motor neuropathy ( )
Distal hereditary motor neuropathy type 2 ( )
Chronic obstructive pulmonary disease ( )
UniProt ID
FBX38_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00646
Sequence
MGPRKKSVKTCIMNNEIPEEMTADETKDYMNQLSHEVLCHIFRYLPLQDIMCMECLSRKL
KEAVTLYLRVVRVVDLCAGRWWEYMPSGFTDASFLTLLKKMPDVEQLYGLHPRYLERRRV
RGHEAFSIPGVLEALQACPNLVGVETSHLELVESIWTYMPHVHILGKFRNRNGAFPIPPE
NKLKIPIGAKIQTLHLVGVNVPEIPCIPMLRHLYMKWVRLTKPQPFKDFLCISLRTFVMR
NCAGPTNSLKYVPLVTGLASARNLEHLEMVRVPFLGGLIQHVVEDSWRSGGFRNLHTIVL
GACKNALEVDLGYLIITAARRLHEVRIQPSLTKDGVFSALKMAELEFPQFETLHLGYVDE
FLLQSRMANADLVKYGLADVVENPGIITDIGMKAVNEVFSCIKYLAIYNCPHLHNPYNWI
SDHSRWTRLVDINLVRCHALKLDSFGQFIELLPSLEFISLDQMFREPPKGCARVGLSAGT
GIGVSSALVSNQNSNNDDNNAQNNNANIHDNNHHHPDDSDEENDFRQDLQPGEQQFAADA
LNEMEDIVQEDGEVVAESGNNTPAHSQAIIPVDVDEEQAGPSGLQRVVKPTSITVHDSES
DDEEDSLELQEVWIPKNGTRRYSEREEKTGESVQSRELSVSGKGKTPLRKRYNSHQMGQS
KQFPLEESSCEKGCQVTSEQIKADMKAARDIPEKKKNKDVYPSCSSTTASTVGNSSSHNT
ASQSPDFVRTVNSGGSSEPSPTEVDVSRQCACSPGGSEDSEAMEEGDAESSVCPRCCCHR
PQESQRRTSRCSDEERPSTSRACVVNGPDGTRSAFSFRTLPQGGSSGPAHDERTNGSGSG
ATGEDRRGSSQPESCDVQSNEDYPRRPLTRARSRLSHVLLVSESEVAKTKPRHAMKRKRT
ADKSTSTSDPVIEDDHVQVLVLKSKNLVGVTMTNCGITDLVLKDCPKMMFIHATRCRVLK
HLKVENAPIVNRFDYAQCKKLNMDQVLDQILRMPPERNRIIYLRPMQQVDTLTLEQKLFS
GPYPYHICIIHEFSNPPNVRNKVRIRSWMDTIANINQELIKYEFFPEATRSEEDLKKYPK
YPWGREIYTLEGVVDGAPYSMISDFPWLRSLRAAEPNSFARYDFEDDEESTIYAPRRKGQ
LSADICMETIGEEISEMRQMKKGVFQRVVAIFIHYCDVNGEPVEDDYI
Function
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of PDCD1/PD-1, thereby regulating T-cells-mediated immunity. Required for anti-tumor activity of T-cells by promoting the degradation of PDCD1/PD-1; the PDCD1-mediated inhibitory pathway being exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival. May indirectly stimulate the activity of transcription factor KLF7, a regulator of neuronal differentiation, without promoting KLF7 ubiquitination.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive distal spinal muscular atrophy 2 DIS0ASM5 Strong GermlineCausalMutation [1]
Neoplasm DISZKGEW Strong Biomarker [2]
Neuronopathy, distal hereditary motor, type 2D DIS0QMLK Strong Autosomal dominant [1]
Distal hereditary motor neuropathy DISGS2ID Moderate Autosomal dominant [3]
Distal hereditary motor neuropathy type 2 DIS162V1 Supportive Autosomal dominant [1]
Chronic obstructive pulmonary disease DISQCIRF Limited 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
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of F-box only protein 38 (FBXO38). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of F-box only protein 38 (FBXO38). [9]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of F-box only protein 38 (FBXO38). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of F-box only protein 38 (FBXO38). [12]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of F-box only protein 38 (FBXO38). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of F-box only protein 38 (FBXO38). [7]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of F-box only protein 38 (FBXO38). [8]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of F-box only protein 38 (FBXO38). [10]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of F-box only protein 38 (FBXO38). [13]
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References

1 A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. Am J Hum Genet. 2013 Nov 7;93(5):976-83. doi: 10.1016/j.ajhg.2013.10.006. Epub 2013 Oct 24.
2 FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells.Nature. 2018 Dec;564(7734):130-135. doi: 10.1038/s41586-018-0756-0. Epub 2018 Nov 28.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Analysis of genetically driven alternative splicing identifies FBXO38 as a novel COPD susceptibility gene.PLoS Genet. 2019 Jul 3;15(7):e1008229. doi: 10.1371/journal.pgen.1008229. eCollection 2019 Jul.
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 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.
8 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
9 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
10 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.
11 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.
12 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.
13 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.