Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK1L8VX)

DOT Name Kyphoscoliosis peptidase (KY)
Synonyms EC 3.4.-.-
Gene Name KY
Related Disease
Hereditary spastic paraplegia ( )
Myofibrillar myopathy 7 ( )
Myopathy ( )
Neuromuscular disease ( )
Congenital myopathy ( )
Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome ( )
Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome ( )
UniProt ID
KY_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.4.-.-
Pfam ID
PF01841
Sequence
MELKKDINAVSIDMLLIVHSEKRRAAQGTLSDQQANPSSLLQRGGGFQGVGNGVRRWQKL
EGNDFHENLVEKQHPQQPQVITSYNSQGTQLTVEVHPRDAMPQLLKKFSLAKRLQGDKNG
NTRPRQPGGKDAHAYPWDRSSLKSMSLDLQQFEKLDIYASQVTAKSGLDELVSDLLQEAH
TDLERVRAIWIWICHHIEYDIAAAQEKDRQAFKPTDILRTQKTNCDGYAGLFERMCRLAG
VQCMTVPGYSKGFGYQTGQSFSGEFDHAWNAVYLEGRWHLVDSTWGSGLVDTITSKFTFL
YNEFYFLTHPALFIEDHFPDNKNWQLLKPPQSLRQFENNMYHKSEFYNKGMLSAHPETSM
IRTVNGKATVTIESCAPTLFMFMLNGKQEHGLLSLRKNGMKLEVYPPTMGTHKLQIFAKG
NSDIYSSVLEYTLKCNYVDMGVQLPAELHQPVGPSWFSEQMGIMKPSHPDPIIHTSDGRC
SISFSVEEGINVLASLHGDDGPITEETQRRYIFQLHREKQTELKVQLPHAGKFALKIFVK
KRQEPGNYIFVFNYLVCCANTKVNWPMFPESFGNWGQDNELLEPLSGVLPANRNVPFKLK
LHGIAKVLVKGQDTWPLTLNHEGYWEGSCSTAGCQEVYVMVLENANHNFYSYILKYKVNA
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Function
Probable cytoskeleton-associated protease required for normal muscle growth. Involved in function, maturation and stabilization of the neuromuscular junction. May act by cleaving muscle-specific proteins such as FLNC.
Tissue Specificity Highly expressed in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hereditary spastic paraplegia DISGZQV1 Strong CausalMutation [1]
Myofibrillar myopathy 7 DISY3XHI Strong Autosomal recessive [2]
Myopathy DISOWG27 Strong Biomarker [3]
Neuromuscular disease DISQTIJZ Strong Genetic Variation [4]
Congenital myopathy DISLSK9G moderate Biomarker [5]
Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome DISCJZO8 Supportive Autosomal recessive [1]
Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome DISNX3L0 Supportive Autosomal recessive [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
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 Kyphoscoliosis peptidase (KY). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Kyphoscoliosis peptidase (KY). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Kyphoscoliosis peptidase (KY). [10]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Kyphoscoliosis peptidase (KY). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Kyphoscoliosis peptidase (KY). [9]
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References

1 Progressive hereditary spastic paraplegia caused by a homozygous KY mutation. Eur J Hum Genet. 2017 Aug;25(8):966-972. doi: 10.1038/ejhg.2017.85. Epub 2017 May 10.
2 The kyphoscoliosis (ky) mouse is deficient in hypertrophic responses and is caused by a mutation in a novel muscle-specific protein. Hum Mol Genet. 2001 Jan 1;10(1):9-16. doi: 10.1093/hmg/10.1.9.
3 Transcriptional upregulation of Bag3, a chaperone-assisted selective autophagy factor, in animal models of KY-deficient hereditary myopathy.Dis Model Mech. 2018 Jul 6;11(7):dmm033225. doi: 10.1242/dmm.033225.
4 A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency.Eur J Hum Genet. 2016 Dec;24(12):1771-1777. doi: 10.1038/ejhg.2016.98. Epub 2016 Aug 3.
5 Kyphoscoliosis peptidase (KY) mutation causes a novel congenital myopathy with core targetoid defects. Acta Neuropathol. 2016 Sep;132(3):475-8. doi: 10.1007/s00401-016-1602-9. Epub 2016 Aug 2.
6 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
7 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.
8 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.
9 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.
10 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.