General Information of Drug Off-Target (DOT) (ID: OTP8YV25)

DOT Name Iron-sulfur cluster co-chaperone protein HscB (HSCB)
Synonyms DnaJ homolog subfamily C member 20
Gene Name HSCB
Related Disease
Anemia, sideroblastic, 5 ( )
UniProt ID
HSC20_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3BVO
Pfam ID
PF18256 ; PF07743
Sequence
MWRGRAGALLRVWGFWPTGVPRRRPLSCDAASQAGSNYPRCWNCGGPWGPGREDRFFCPQ
CRALQAPDPTRDYFSLMDCNRSFRVDTAKLQHRYQQLQRLVHPDFFSQRSQTEKDFSEKH
STLVNDAYKTLLAPLSRGLYLLKLHGIEIPERTDYEMDRQFLIEIMEINEKLAEAESEAA
MKEIESIVKAKQKEFTDNVSSAFEQDDFEEAKEILTKMRYFSNIEEKIKLKKIPL
Function
[Iron-sulfur cluster co-chaperone protein HscB, mitochondrial]: Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain. Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. Plays an essential role in hematopoiesis; [Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic]: Acts as a co-chaperone in iron-sulfur cluster assembly in the cytoplasm. Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1. This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT.
Tissue Specificity Expressed in lung, brain, stomach, spleen, ovary, testis, liver, muscle and heart.
Reactome Pathway
Mitochondrial iron-sulfur cluster biogenesis (R-HSA-1362409 )
Mitochondrial protein import (R-HSA-1268020 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anemia, sideroblastic, 5 DISPMBY3 Limited Unknown [1]
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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 Iron-sulfur cluster co-chaperone protein HscB (HSCB). [2]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [4]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [5]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [6]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [7]
Liothyronine DM6IR3P Approved Liothyronine decreases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [3]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [9]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [10]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Iron-sulfur cluster co-chaperone protein HscB (HSCB). [11]
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⏷ Show the Full List of 10 Drug(s)

References

1 Mutations in the iron-sulfur cluster biogenesis protein HSCB cause congenital sideroblastic anemia. J Clin Invest. 2020 Oct 1;130(10):5245-5256. doi: 10.1172/JCI135479.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
6 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
7 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
8 Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
9 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.
10 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
11 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.