Details of Drug Off-Target (DOT)

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

DOT Name Elongation factor-like GTPase 1 (EFL1)
Synonyms Elongation factor Tu GTP-binding domain-containing protein 1; Elongation factor-like 1; Protein FAM42A
Gene Name EFL1
Related Disease
T-cell acute lymphoblastic leukaemia ( )
Hepatitis C virus infection ( )
Salla disease ( )
Shwachman-Diamond syndrome 2 ( )
Shwachman-Diamond syndrome ( )
UniProt ID
EFL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5ANB; 5ANC
Pfam ID
PF00679 ; PF14492 ; PF00009
Sequence
MVLNSLDKMIQLQKNTANIRNICVLAHVDHGKTTLADCLISSNGIISSRLAGKLRYMDSR
EDEQIRGITMKSSAISLHYATGNEEYLINLIDSPGHVDFSSEVSTAVRICDGCIIVVDAV
EGVCPQTQAVLRQAWLENIRPVLVINKIDRLIVELKFTPQEAYSHLKNILEQINALTGTL
FTSKVLEERAERETESQVNPNSEQGEQVYDWSTGLEDTDDSHLYFSPEQGNVVFTSAIDG
WGFGIEHFARIYSQKIGIKKEVLMKTLWGDYYINMKAKKIMKGDQAKGKKPLFVQLILEN
IWSLYDAVLKKDKDKIDKIVTSLGLKIGAREARHSDPKVQINAICSQWLPISHAVLAMVC
QKLPSPLDITAERVERLMCTGSQTFDSFPPETQALKAAFMKCGSEDTAPVIIFVSKMFAV
DAKALPQNKPRPLTQEEIAQRRERARQRHAEKLAAAQGQAPLEPTQDGSAIETCPKGEEP
RGDEQQVESMTPKPVLQEENNQESFIAFARVFSGVARRGKKIFVLGPKYSPLEFLRRVPL
GFSAPPDGLPQVPHMAYCALENLYLLMGRELEYLEEVPPGNVLGIGGLQDFVLKSATLCS
LPSCPPFIPLNFEATPIVRVAVEPKHPSEMPQLVKGMKLLNQADPCVQILIQETGEHVLV
TAGEVHLQRCLDDLKERFAKIHISVSEPIIPFRETITKPPKVDMVNEEIGKQQKVAVIHQ
MKEDQSKIPEGIQVDSDGLITITTPNKLATLSVRAMPLPEEVTQILEENSDLIRSMEQLT
SSLNEGENTHMIHQKTQEKIWEFKGKLEQHLTGRRWRNIVDQIWSFGPRKCGPNILVNKS
EDFQNSVWTGPADKASKEASRYRDLGNSIVSGFQLATLSGPMCEEPLMGVCFVLEKWDLS
KFEEQGASDLAKEGQEENETCSGGNENQELQDGCSEAFEKRTSQKGESPLTDCYGPFSGQ
LIATMKEACRYALQVKPQRLMAAMYTCDIMATGDVLGRVYAVLSKREGRVLQEEMKEGTD
MFIIKAVLPVAESFGFADEIRKRTSGLASPQLVFSHWEIIPSDPFWVPTTEEEYLHFGEK
ADSENQARKYMNAVRKRKGLYVEEKIVEHAEKQRTLSKNK
Function
Involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with SBDS, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Has low intrinsic GTPase activity. GTPase activity is increased by contact with 60S ribosome subunits.
Tissue Specificity Expressed at low levels in brain. Expression is highly increased in glioma tissues.
KEGG Pathway
Ribosome biogenesis in eukaryotes (hsa03008 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
T-cell acute lymphoblastic leukaemia DIS17AI2 Definitive Genetic Variation [1]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [2]
Salla disease DISA4PBW Strong Altered Expression [3]
Shwachman-Diamond syndrome 2 DISHVJG8 Moderate Autosomal recessive [4]
Shwachman-Diamond syndrome DISW57NW Supportive Autosomal recessive [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Elongation factor-like GTPase 1 (EFL1). [6]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Elongation factor-like GTPase 1 (EFL1). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Elongation factor-like GTPase 1 (EFL1). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Elongation factor-like GTPase 1 (EFL1). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Elongation factor-like GTPase 1 (EFL1). [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Elongation factor-like GTPase 1 (EFL1). [11]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Elongation factor-like GTPase 1 (EFL1). [12]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Elongation factor-like GTPase 1 (EFL1). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Elongation factor-like GTPase 1 (EFL1). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Elongation factor-like GTPase 1 (EFL1). [16]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Elongation factor-like GTPase 1 (EFL1). [17]
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⏷ Show the Full List of 11 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Elongation factor-like GTPase 1 (EFL1). [13]
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References

1 The T-cell leukemia related rpl10-R98S mutant traps the 60S export adapter Nmd3 in the ribosomal P site in yeast.PLoS Genet. 2017 Jul 17;13(7):e1006894. doi: 10.1371/journal.pgen.1006894. eCollection 2017 Jul.
2 Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis.Ann Intern Med. 1992 Jan 1;116(1):21-5. doi: 10.7326/0003-4819-116-1-21.
3 Arabidopsis ELF4-like proteins EFL1 and EFL3 influence flowering time.Gene. 2019 Jun 5;700:131-138. doi: 10.1016/j.gene.2019.03.047. Epub 2019 Mar 24.
4 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.
5 Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in aShwachman-Diamond like syndrome. J Med Genet. 2017 Aug;54(8):558-566. doi: 10.1136/jmedgenet-2016-104366. Epub 2017 Mar 22.
6 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
7 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.
8 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
13 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.
14 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
15 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.
16 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.