Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJD4K8A)

DOT Name	Glutaminyl-peptide cyclotransferase-like protein (QPCTL)
Synonyms	EC 2.3.2.5; Golgi-resident glutaminyl-peptide cyclotransferase; isoQC; gQC
Gene Name	QPCTL
Related Disease	Advanced cancer ( ) Amyloidosis ( ) Burkitt lymphoma ( ) Obesity ( ) Rheumatoid arthritis ( )
UniProt ID	QPCTL_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3PB4; 3PB6; 3PB7; 3PB8; 3PB9
EC Number	2.3.2.5
Pfam ID	PF04389
Sequence	MRSGGRGRPRLRLGERGLMEPLLPPKRRLLPRVRLLPLLLALAVGSAFYTIWSGWHRRTE ELPLGRELRVPLIGSLPEARLRRVVGQLDPQRLWSTYLRPLLVVRTPGSPGNLQVRKFLE ATLRSLTAGWHVELDPFTASTPLGPVDFGNVVATLDPRAARHLTLACHYDSKLFPPGSTP FVGATDSAVPCALLLELAQALDLELSRAKKQAAPVTLQLLFLDGEEALKEWGPKDSLYGS RHLAQLMESIPHSPGPTRIQAIELFMLLDLLGAPNPTFYSHFPRTVRWFHRLRSIEKRLH RLNLLQSHPQEVMYFQPGEPFGSVEDDHIPFLRRGVPVLHLISTPFPAVWHTPADTEVNL HPPTVHNLCRILAVFLAEYLGL
Function	Responsible for the biosynthesis of pyroglutamyl peptides.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amyloidosis	DISHTAI2	Strong	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Glutaminyl-peptide cyclotransferase-like protein (QPCTL).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glutaminyl-peptide cyclotransferase-like protein (QPCTL).	[7]
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References

1	Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRP axis and a target for cancer immunotherapy.Nat Med. 2019 Apr;25(4):612-619. doi: 10.1038/s41591-019-0356-z. Epub 2019 Mar 4.
2	Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated A is induced by pyroglutamate-A formation.J Neurosci. 2011 Sep 7;31(36):12790-801. doi: 10.1523/JNEUROSCI.1794-11.2011.
3	Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma is directly mediated through the promoter G-quadruplex.J Biol Chem. 2011 Nov 25;286(47):41018-27. doi: 10.1074/jbc.M111.274720. Epub 2011 Sep 28.
4	A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity.Int J Obes (Lond). 2015 Feb;39(2):295-302. doi: 10.1038/ijo.2014.96. Epub 2014 Jun 3.
5	Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis-A pilot study.Arch Oral Biol. 2019 Jan;97:223-230. doi: 10.1016/j.archoralbio.2018.10.022. Epub 2018 Oct 28.
6	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.
7	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.