Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVH9HD8)

DOT Name	Membralin (TMEM259)
Synonyms	Transmembrane protein 259
Gene Name	TMEM259
Related Disease	Acute myelogenous leukaemia ( )
UniProt ID	MBRL_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF09746
Sequence	MSEHVEPAAPGPGPNGGGGGPAPARGPRTPNLNPNPLINVRDRLFHALFFKMAVTYSRLF PPAFRRLFEFFVLLKALFVLFVLAYIHIVFSRSPINCLEHVRDKWPREGILRVEVRHNSS RAPVFLQFCDSGGRGSFPGLAVEPGSNLDMEDEEEEELTMEMFGNSSIKFELDIEPKVFK PPSSTEALNDSQEFPFPETPTKVWPQDEYIVEYSLEYGFLRLSQATRQRLSIPVMVVTLD PTRDQCFGDRFSRLLLDEFLGYDDILMSSVKGLAENEENKGFLRNVVSGEHYRFVSMWMA RTSYLAAFAIMVIFTLSVSMLLRYSHHQIFVFIVDLLQMLEMNMAIAFPAAPLLTVILAL VGMEAIMSEFFNDTTTAFYIILIVWLADQYDAICCHTSTSKRHWLRFFYLYHFAFYAYHY RFNGQYSSLALVTSWLFIQHSMIYFFHHYELPAILQQVRIQEMLLQAPPLGPGTPTALPD DMNNNSGAPATAPDSAGQPPALGPVSPGASGSPGPVAAAPSSLVAAAASVAAAAGGDLGW MAETAAIITDASFLSGLSASLLERRPASPLGPAGGLPHAPQDSVPPSDSAASDTTPLGAA VGGPSPASMAPTEAPSEVGS
Function	May have a role in the ERAD pathway required for clearance of misfolded proteins in the endoplasmic reticulum (ER). Promotes survival of motor neurons, probably by protecting against ER stress.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Membralin (TMEM259) affects the response to substance of Methotrexate.	[11]
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2 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 Membralin (TMEM259).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Membralin (TMEM259).	[9]
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7 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 Membralin (TMEM259).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Membralin (TMEM259).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Membralin (TMEM259).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Membralin (TMEM259).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Membralin (TMEM259).	[7]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Membralin (TMEM259).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Membralin (TMEM259).	[10]
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⏷ Show the Full List of 7 Drug(s)

References

1	Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
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	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.
5	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.
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	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
8	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
9	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.
10	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
11	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.