Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT264P6X)

• DOT Name: DnaJ homolog subfamily B member 13 (DNAJB13)
• Synonyms: Testis and spermatogenesis cell-related protein 6; Testis spermatocyte apoptosis-related gene 6 protein; Testis spermatogenesis apoptosis-related gene 3 protein; Testis spermatogenesis apoptosis-related gene 6 protein
• Gene Name: DNAJB13
• Related Disease:
  Male infertility
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia 34
  Primary ciliary dyskinesia
  Spermatogenic failure 16
• UniProt ID: DJB13_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00226 ; PF01556
• Sequence:
  MGQDYYSVLGITRNSEDAQIKQAYRRLALKHHPLKSNEPSSAEIFRQIAEAYDVLSDPMK
  RGIYDKFGEEGLKGGIPLEFGSQTPWTTGYVFHGKPEKVFHEFFGGNNPFSEFFDAEGSE
  VDLNFGGLQGRGVKKQDPQVERDLYLSLEDLFFGCTKKIKISRRVLNEDGYSSTIKDKIL
  TIDVKPGWRQGTRITFEKEGDQGPNIIPADIIFIVKEKLHPRFRRENDNLFFVNPIPLGK
  ALTCCTVEVRTLDDRLLNIPINDIIHPKYFKKVPGEGMPLPEDPTKKGDLFIFFDIQFPT
  RLTPQKKQMLRQALLT
• Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
• Tissue Specificity: Specifically expressed in testis and trachea.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Biomarker	[1]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[2]
Primary ciliary dyskinesia 34	DISBXA78	Strong	Autosomal recessive	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[2]
Spermatogenic failure 16	DISJT1VL	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DnaJ homolog subfamily B member 13 (DNAJB13).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DnaJ homolog subfamily B member 13 (DNAJB13).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of DnaJ homolog subfamily B member 13 (DNAJB13).	[8]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of DnaJ homolog subfamily B member 13 (DNAJB13).	[9]

2 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 increases the methylation of DnaJ homolog subfamily B member 13 (DNAJB13).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DnaJ homolog subfamily B member 13 (DNAJB13).	[7]

References

• [1] Transcriptomic Analysis Reveals Insights on Male Infertility in Octopus maya Under Chronic Thermal Stress.Front Physiol. 2019 Jan 15;9:1920. doi: 10.3389/fphys.2018.01920. eCollection 2018.
• [2] Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility. Am J Hum Genet. 2016 Aug 4;99(2):489-500. doi: 10.1016/j.ajhg.2016.06.022.
• [3] Mechanistic insights into acephalic spermatozoa syndrome-associated mutations in the human SUN5 gene.J Biol Chem. 2018 Feb 16;293(7):2395-2407. doi: 10.1074/jbc.RA117.000861. Epub 2018 Jan 3.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [9] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.