Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTX5TF0)

DOT Name Meiosis-specific with OB domain-containing protein (MEIOB)
Synonyms EC 3.1.-.-
Gene Name MEIOB
Related Disease
Azoospermia ( )
Lung cancer ( )
Lung carcinoma ( )
Spermatogenic failure 22 ( )
Testicular cancer ( )
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation ( )
Female hypogonadism ( )
UniProt ID
MEIOB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.-.-
Sequence
MANSFAARIFTTLSDLQTNMANLKVIGIVIGKTDVKGFPDRKNIGSERYTFSFTIRDSPA
HFVNAASWGNEDYIKSLSDSFRVGDCVIIENPLIQRKEIEREEKFSPATPSNCKLLLSEN
HSTVKVCSSYEVDTKLLSLIHLPVKESHDYYSLGDIVANGHSLNGRIINVLAAVKSVGEP
KYFTTSDRRKGQRCEVRLYDETESSFAMTCWDNESILLAQSWMPRETVIFASDVRINFDK
FRNCMTATVISKTIITTNPDIPEANILLNFIRENKETNVLDDEIDSYFKESINLSTIVDV
YTVEQLKGKALKNEGKADPSYGILYAYISTLNIDDETTKVVRNRCSSCGYIVNEASNMCT
TCNKNSLDFKSVFLSFHVLIDLTDHTGTLHSCSLTGSVAEETLGCTFVLSHRARSGLKIS
VLSCKLADPTEASRNLSGQKHV
Function
Single-stranded DNA-binding protein required for homologous recombination in meiosis I. Required for double strand breaks (DSBs) repair and crossover formation and promotion of faithful and complete synapsis. Not required for the initial loading of recombinases but required to maintain a proper number of RAD51 and DMC1 foci after the zygotene stage. May act by ensuring the stabilization of recombinases, which is required for successful homology search and meiotic recombination. Displays Single-stranded DNA 3'-5' exonuclease activity in vitro.
Tissue Specificity In fetal gonads, specifically expressed in the ovary starting at the 14th weeks post fertilization . In the adult, restricted to testis .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Azoospermia DIS94181 Strong Genetic Variation [1]
Lung cancer DISCM4YA Strong Altered Expression [2]
Lung carcinoma DISTR26C Strong Altered Expression [2]
Spermatogenic failure 22 DISDJZQZ Strong Autosomal recessive [3]
Testicular cancer DIS6HNYO Strong Biomarker [2]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation DIS56JR8 Supportive Autosomal dominant [4]
Female hypogonadism DISWASB4 Limited Genetic Variation [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Meiosis-specific with OB domain-containing protein (MEIOB). [6]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Meiosis-specific with OB domain-containing protein (MEIOB). [7]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Meiosis-specific with OB domain-containing protein (MEIOB). [8]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Meiosis-specific with OB domain-containing protein (MEIOB). [8]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Meiosis-specific with OB domain-containing protein (MEIOB). [9]
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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 increases the methylation of Meiosis-specific with OB domain-containing protein (MEIOB). [10]
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References

1 A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest.Hum Reprod. 2019 Apr 1;34(4):666-671. doi: 10.1093/humrep/dez016.
2 Identification of a meiosis-specific protein, MEIOB, as a novel cancer/testis antigen and its augmented expression in demethylated cancer cells.Immunol Lett. 2014 Mar-Apr;158(1-2):175-82. doi: 10.1016/j.imlet.2014.01.004. Epub 2014 Jan 16.
3 MEIOB targets single-strand DNA and is necessary for meiotic recombination. PLoS Genet. 2013;9(9):e1003784. doi: 10.1371/journal.pgen.1003784. Epub 2013 Sep 19.
4 A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes. Genet Med. 2017 Sep;19(9):998-1006. doi: 10.1038/gim.2016.225. Epub 2017 Feb 16.
5 A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks.EBioMedicine. 2019 Apr;42:524-531. doi: 10.1016/j.ebiom.2019.03.075. Epub 2019 Apr 15.
6 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
7 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
8 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
9 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.
10 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.