Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFBXX2H)

DOT Name Protein SHQ1 homolog (SHQ1)
Gene Name SHQ1
Related Disease
Bone marrow failure syndrome ( )
Cerebellar degeneration ( )
Dyskeratosis congenita ( )
Dyskeratosis congenita, X-linked ( )
Neoplasm ( )
Nervous system disease ( )
Neurodevelopmental disorder with dystonia and seizures ( )
Non-small-cell lung cancer ( )
Prostate neoplasm ( )
T-cell acute lymphoblastic leukaemia ( )
Advanced cancer ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
UniProt ID
SHQ1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2MNW; 4PBD; 4PCK
Pfam ID
PF04925 ; PF21413
Sequence
MLTPAFDLSQDPDFLTIAIRVPYARVSEFDVYFEGSDFKFYAKPYFLRLTLPGRIVENGS
EQGSYDADKGIFTIRLPKETPGQHFEGLNMLTALLAPRKSRTAKPLVEEIGASEIPEEVV
DDEEFDWEIEQTPCEEVSESALNPQCHYGFGNLRSGVLQRLQDELSDVIDIKDPDFTPAA
ERRQKRLAAELAKFDPDHYLADFFEDEAIEQILKYNPWWTDKYSKMMAFLEKSQEQENHA
TLVSFSEEEKYQLRKFVNKSYLLDKRACRQVCYSLIDILLAYCYETRVTEGEKNVESAWN
IRKLSPTLCWFETWTNVHDIMVSFGRRVLCYPLYRHFKLVMKAYRDTIKILQLGKSAVLK
CLLDIHKIFQENDPAYILNDLYISDYCVWIQKVKSKKLAALAEALKEVSLTKAQLGLELE
ELEAAALLVQEEETALKAAHSVSGQQTLCSSSEASDSEDSDSSVSSGNEDSGSDSEQDEL
KDSPSETVSSLQGPFLEESSAFLIVDGGVRRNTAIQESDASQGKPLASSWPLGVSGPLIE
ELGEQLKTTVQVSEPKGTTAVNRSNIQERDGCQTPNN
Function
Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.
Reactome Pathway
Telomere Extension By Telomerase (R-HSA-171319 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bone marrow failure syndrome DISVUY1J Strong Biomarker [1]
Cerebellar degeneration DISPBCM3 Strong Genetic Variation [1]
Dyskeratosis congenita DISSXV0K Strong Genetic Variation [1]
Dyskeratosis congenita, X-linked DISJ3Y69 Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Nervous system disease DISJ7GGT Strong Genetic Variation [1]
Neurodevelopmental disorder with dystonia and seizures DIS7UBD2 Strong Autosomal recessive [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [3]
Prostate neoplasm DISHDKGQ Strong Altered Expression [4]
T-cell acute lymphoblastic leukaemia DIS17AI2 Strong Biomarker [5]
Advanced cancer DISAT1Z9 moderate Biomarker [6]
Head and neck cancer DISBPSQZ Disputed Genetic Variation [6]
Head and neck carcinoma DISOU1DS Disputed Genetic Variation [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Protein SHQ1 homolog (SHQ1). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Protein SHQ1 homolog (SHQ1). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Protein SHQ1 homolog (SHQ1). [11]
------------------------------------------------------------------------------------
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein SHQ1 homolog (SHQ1). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein SHQ1 homolog (SHQ1). [9]
------------------------------------------------------------------------------------

References

1 Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita. Mol Genet Genomic Med. 2017 Nov;5(6):805-808. doi: 10.1002/mgg3.314. Epub 2017 Aug 15.
2 Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita.Hum Mol Genet. 2009 Dec 1;18(23):4546-51. doi: 10.1093/hmg/ddp416. Epub 2009 Sep 4.
3 Reversed expression of GRIM-1 and GRP78 in human non-small cell lung cancer.Hum Pathol. 2014 Sep;45(9):1936-43. doi: 10.1016/j.humpath.2014.04.023. Epub 2014 Jun 18.
4 GRIM-1, a novel growth suppressor, inhibits rRNA maturation by suppressing small nucleolar RNAs.PLoS One. 2011;6(9):e24082. doi: 10.1371/journal.pone.0024082. Epub 2011 Sep 8.
5 SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival.Nat Commun. 2018 Oct 15;9(1):4281. doi: 10.1038/s41467-018-06523-4.
6 Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis.Nat Commun. 2017 Oct 20;8(1):1081. doi: 10.1038/s41467-017-01198-9.
7 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.
8 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.
9 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
10 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.