Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBD8O8Y)

DOT Name	Metaxin-2 (MTX2)
Synonyms	Mitochondrial outer membrane import complex protein 2
Gene Name	MTX2
Related Disease	Mandibuloacral dysplasia progeroid syndrome ( ) Mandibuloacral dysplasia ( ) Alopecia ( )
UniProt ID	MTX2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF17171 ; PF10568
Sequence	MSLVAEAFVSQIAAAEPWPENATLYQQLKGEQILLSDNAASLAVQAFLQMCNLPIKVVCR ANAEYMSPSGKVPFIHVGNQVVSELGPIVQFVKAKGHSLSDGLEEVQKAEMKAYMELVNN MLLTAELYLQWCDEATVGEITHARYGSPYPWPLNHILAYQKQWEVKRKMKAIGWGKKTLD QVLEDVDQCCQALSQRLGTQPYFFNKQPTELDALVFGHLYTILTTQLTNDELSEKVKNYS NLLAFCRRIEQHYFEDRGKGRLS
Function	Involved in transport of proteins into the mitochondrion.
KEGG Pathway	Mitophagy - animal (hsa04137 )
Reactome Pathway	Cristae formation (R-HSA-8949613 ) Mitochondrial protein import (R-HSA-1268020 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Mandibuloacral dysplasia progeroid syndrome	DISGW6SI	Strong	Autosomal recessive	[1]
Mandibuloacral dysplasia	DISMOYL1	Supportive	Autosomal recessive	[1]
Alopecia	DIS37HU4	Limited	Genetic Variation	[2]
------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

1 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 Metaxin-2 (MTX2).	[3]
------------------------------------------------------------------------------------

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Metaxin-2 (MTX2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Metaxin-2 (MTX2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Metaxin-2 (MTX2).	[6]
------------------------------------------------------------------------------------

References

1	Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. Nat Commun. 2020 Sep 11;11(1):4589. doi: 10.1038/s41467-020-18146-9.
2	Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
3	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.
4	Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
5	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.