Details of Drug Off-Target (DOT)

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

DOT Name	Carboxypeptidase Q (CPQ)
Synonyms	EC 3.4.17.-; Lysosomal dipeptidase; Plasma glutamate carboxypeptidase
Gene Name	CPQ
Related Disease	Acute myelogenous leukaemia ( ) Behcet disease ( ) Malaria ( ) Neoplasm ( ) Advanced cancer ( ) Ankylosing spondylitis ( ) B-cell neoplasm ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Fibromyalgia ( ) Glioma ( ) Hepatitis C virus infection ( ) High blood pressure ( ) Huntington disease ( ) Hyperthyroidism ( ) Immunodeficiency ( ) Intervertebral disc degeneration ( ) Kidney neoplasm ( ) Liver cancer ( ) Lung cancer ( ) Lung carcinoma ( ) Melanoma ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Pancreatic adenocarcinoma ( ) Papillary renal cell carcinoma ( ) Postmenopausal osteoporosis ( ) Psoriasis ( ) Renal cell carcinoma ( ) Visceral leishmaniasis ( ) Autoimmune disease ( ) Bone osteosarcoma ( ) Coronary heart disease ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Squamous cell carcinoma ( ) Type-1/2 diabetes ( ) Brucellosis ( ) Breast cancer ( ) Breast carcinoma ( ) Neurodevelopmental disorder ( ) Rheumatoid arthritis ( )
UniProt ID	CBPQ_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.4.17.-
Pfam ID	PF04389
Sequence	MKFLIFAFFGGVHLLSLCSGKAICKNGISKRTFEEIKEEIASCGDVAKAIINLAVYGKAQ NRSYERLALLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLEKVHLEPVRIPHWERGEESA VMLEPRIHKIAILGLGSSIGTPPEGITAEVLVVTSFDELQRRASEARGKIVVYNQPYINY SRTVQYRTQGAVEAAKVGALASLIRSVASFSIYSPHTGIQEYQDGVPKIPTACITVEDAE MMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYPEQVVLVSGHLDSWDVGQGA MDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLV MESDAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITQVLSHGEGTDINFWIQAGVPGA SLLDDLYKYFFFHHSHGDTMTVMDPKQMNVAAAVWAVVSYVVADMEEMLPRS
Function	Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides. Catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids. May play a role in the liberation of thyroxine hormone from its thyroglobulin (Tg) precursor.
Tissue Specificity	Mainly detected in blood plasma. Abundant in placenta and kidney. Present at low level in muscles, liver and skin fibroblasts. Not detected in brain or white blood cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Behcet disease	DISSYMBS	Definitive	Genetic Variation	[2]
Malaria	DISQ9Y50	Definitive	Altered Expression	[3]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[6]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[7]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Fibromyalgia	DISZJDS2	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[13]
High blood pressure	DISY2OHH	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Altered Expression	[15]
Hyperthyroidism	DISX87ZH	Strong	Altered Expression	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[17]
Intervertebral disc degeneration	DISG3AIM	Strong	Altered Expression	[18]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[19]
Liver cancer	DISDE4BI	Strong	Altered Expression	[8]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[20]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[20]
Melanoma	DIS1RRCY	Strong	Biomarker	[21]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[23]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[9]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[24]
Psoriasis	DIS59VMN	Strong	Biomarker	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[26]
Autoimmune disease	DISORMTM	moderate	Biomarker	[27]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[28]
Coronary heart disease	DIS5OIP1	moderate	Biomarker	[29]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[28]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[31]
Brucellosis	DISEAYGH	Disputed	Biomarker	[32]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[33]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[33]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[34]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[35]
------------------------------------------------------------------------------------


⏷ Show the Full List of 44 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Carboxypeptidase Q (CPQ) affects the response to substance of Progesterone.	[46]
------------------------------------------------------------------------------------

1 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 Carboxypeptidase Q (CPQ).	[36]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carboxypeptidase Q (CPQ).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carboxypeptidase Q (CPQ).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carboxypeptidase Q (CPQ).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carboxypeptidase Q (CPQ).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carboxypeptidase Q (CPQ).	[41]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Carboxypeptidase Q (CPQ).	[42]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Carboxypeptidase Q (CPQ).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carboxypeptidase Q (CPQ).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Carboxypeptidase Q (CPQ).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carboxypeptidase Q (CPQ).	[45]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

References

1	In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia.Oncotarget. 2017 Jan 24;8(4):6341-6352. doi: 10.18632/oncotarget.13856.
2	Behet's disease: An immunogenetic perspective.J Cell Physiol. 2019 Jun;234(6):8055-8074. doi: 10.1002/jcp.27576. Epub 2018 Oct 20.
3	Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite.PLoS Pathog. 2018 May 16;14(5):e1007031. doi: 10.1371/journal.ppat.1007031. eCollection 2018 May.
4	A Macropinocytosis-Intensifying Albumin Domain-Based scFv Antibody and Its Conjugate Directed against K-Ras Mutant Pancreatic Cancer.Mol Pharm. 2018 Jun 4;15(6):2403-2412. doi: 10.1021/acs.molpharmaceut.8b00234. Epub 2018 May 23.
5	Crystal structures of human procathepsin H.PLoS One. 2018 Jul 25;13(7):e0200374. doi: 10.1371/journal.pone.0200374. eCollection 2018.
6	ERAP1/ERAP2 and RUNX3 polymorphisms are not associated with ankylosing spondylitis susceptibility in Chinese Han.Clin Exp Immunol. 2018 Jul;193(1):95-102. doi: 10.1111/cei.13121. Epub 2018 Mar 30.
7	Emerging therapies for acute myeloid leukemia.J Hematol Oncol. 2017 Apr 18;10(1):93. doi: 10.1186/s13045-017-0463-6.
8	In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe.Chem Sci. 2017 May 1;8(5):3479-3483. doi: 10.1039/c6sc05712h. Epub 2017 Mar 2.
9	Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.Nat Genet. 2015 Jan;47(1):13-21. doi: 10.1038/ng.3146. Epub 2014 Nov 17.
10	Synthesis, docking, cytotoxicity, and LTA(4)H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy.Bioorg Med Chem. 2017 Feb 1;25(3):1277-1285. doi: 10.1016/j.bmc.2016.12.048. Epub 2016 Dec 29.
11	Altered Serum Oxytocinase and Enkephalin-Degrading Aminopeptidase Activities in Patients With Fibromyalgia.Biol Res Nurs. 2019 Jul;21(4):431-439. doi: 10.1177/1099800419854207. Epub 2019 May 26.
12	Differential Effects of Doxazosin on Renin-Angiotensin-System- Regulating Aminopeptidase Activities in Neuroblastoma and Glioma Tumoral Cells.CNS Neurol Disord Drug Targets. 2019;18(1):29-36. doi: 10.2174/1871527317666181029111739.
13	Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the hepatitis C virus-infected liver.J Interferon Cytokine Res. 2007 Dec;27(12):985-90. doi: 10.1089/jir.2007.0039.
14	Whole genome resequencing identifies the CPQ gene as a determinant of ascites syndrome in broilers.PLoS One. 2018 Jan 2;13(1):e0189544. doi: 10.1371/journal.pone.0189544. eCollection 2018.
15	Oxidative stress and plasma aminopeptidase activity in Huntington's disease.J Neural Transm (Vienna). 2010 Mar;117(3):325-32. doi: 10.1007/s00702-009-0364-0. Epub 2010 Jan 22.
16	Cystinyl and pyroglutamyl-beta-naphthylamide hydrolyzing activities are modified coordinately between hypothalamus, liver and plasma depending on the thyroid status of adult male rats.J Physiol Pharmacol. 2018 Apr;69(2). doi: 10.26402/jpp.2018.2.04. Epub 2018 Jun 13.
17	SCID mouse model of Epstein-Barr virus-induced lymphomagenesis of immunodeficient humans.Int J Cancer. 1991 Feb 20;47(4):510-7. doi: 10.1002/ijc.2910470407.
18	Correlation Between Proteolytic Enzymes and Microangiogenesis in Degenerative Intervertebral Disc Nucleus.J Invest Surg. 2021 Jun;34(6):679-684. doi: 10.1080/08941939.2019.1679921. Epub 2019 Dec 18.
19	Proximal CD13 Versus Distal GATA-3 Expression in Renal Neoplasia According to WHO 2016 Classification.Appl Immunohistochem Mol Morphol. 2018 May/Jun;26(5):316-323. doi: 10.1097/PAI.0000000000000435.
20	Hypermethylation of PGCP gene is associated with human bronchial epithelial cells immortalization.Gene. 2018 Feb 5;642:505-512. doi: 10.1016/j.gene.2017.11.063. Epub 2017 Nov 28.
21	ER-aminopeptidase 1 determines the processing and presentation of an immunotherapy-relevant melanoma epitope.Eur J Immunol. 2020 Feb;50(2):270-283. doi: 10.1002/eji.201948116. Epub 2019 Nov 27.
22	Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers.Adv Clin Exp Med. 2016 Jan-Feb;25(1):117-28. doi: 10.17219/acem/60715.
23	Comparison of robotic vs laparoscopic vs open distal pancreatectomy. A systematic review and network meta-analysis.HPB (Oxford). 2019 Oct;21(10):1268-1276. doi: 10.1016/j.hpb.2019.04.010. Epub 2019 May 9.
24	Liuwei Dihuang Pill () Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression.Chin J Integr Med. 2018 Jun;24(6):415-422. doi: 10.1007/s11655-016-2744-2. Epub 2016 Dec 27.
25	Functional Genomics and Its Bench-to-Bedside Translation Pertaining to the Identified Susceptibility Alleles and Loci in Ankylosing Spondylitis.Curr Rheumatol Rep. 2016 Oct;18(10):63. doi: 10.1007/s11926-016-0612-x.
26	A novel recombinant Leishmania donovani p45, a partial coding region of methionine aminopeptidase, generates protective immunity by inducing a Th1 stimulatory response against experimental visceral leishmaniasis.Int J Parasitol. 2012 May 1;42(5):429-35. doi: 10.1016/j.ijpara.2012.02.013. Epub 2012 Mar 27.
27	The role of ERAP1 in autoinflammation and autoimmunity.Hum Immunol. 2019 May;80(5):302-309. doi: 10.1016/j.humimm.2019.02.013. Epub 2019 Feb 25.
28	Possible contribution of aminopeptidase N(APN/CD13) to migration and invasion of human osteosarcoma cell lines.Int J Oncol. 2014 Dec;45(6):2475-85. doi: 10.3892/ijo.2014.2664. Epub 2014 Sep 22.
29	Identification of new genes differentially expressed in coronary artery disease by expression profiling.Physiol Genomics. 2003 Sep 29;15(1):65-74. doi: 10.1152/physiolgenomics.00181.2002.
30	A bispecific fusion protein and a bifunctional enediyne-energized fusion protein consisting of TRAIL, EGFR peptide ligand, and apoprotein of lidamycin against EGFR and DR4/5 show potent antitumor activity.Anticancer Drugs. 2015 Jan;26(1):64-73. doi: 10.1097/CAD.0000000000000160.
31	Renin-angiotensin system inhibitors and angioedema: anesthetic implications.Curr Opin Anaesthesiol. 2012 Jun;25(3):356-62. doi: 10.1097/ACO.0b013e328352dda5.
32	Purification and characterization of an immunogenic aminopeptidase of Brucella melitensis.Infect Immun. 2003 Sep;71(9):5238-44. doi: 10.1128/IAI.71.9.5238-5244.2003.
33	Circulating renin-angiotensin system-regulating specific aminopeptidase activities in pre- and post- menopausal women with breast cancer treated or not with neoadyuvant chemotherapy. A two years follow up study.Breast. 2019 Feb;43:28-30. doi: 10.1016/j.breast.2018.10.010. Epub 2018 Nov 1.
34	Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.Genes Brain Behav. 2018 Feb;17(2):126-138. doi: 10.1111/gbb.12419. Epub 2017 Sep 15.
35	CD13/aminopeptidase N-induced lymphocyte involvement in inflamed joints of patients with rheumatoid arthritis.Arthritis Rheum. 2002 Sep;46(9):2330-8. doi: 10.1002/art.10517.
36	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.
37	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
38	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.
39	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
40	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
41	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
42	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
43	Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
44	Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
45	Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
46	Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.