Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVH64PO)

DOT Name Cytosolic carboxypeptidase 3 (AGBL3)
Synonyms EC 3.4.17.-; ATP/GTP-binding protein-like 3; Protein deglutamylase CCP3
Gene Name AGBL3
Related Disease
Arthritis ( )
Rheumatoid arthritis ( )
Systemic lupus erythematosus ( )
Osteoarthritis ( )
UniProt ID
CBPC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.4.17.-
Pfam ID
PF18027 ; PF00246
Sequence
MSEDSEKEDYSDRTISDEDESDEDMFMKFVSEDLHRCALLTADSFGDPFFPRTTQILLEY
QLGRWVPRLREPRDLYGVSSSGPLSPTRWPYHCEVIDEKVQHIDWTPSCPEPVYIPTGLE
TEPLYPDSKEATVVYLAEDAYKEPCFVYSRVGGNRTPLKQPVDYRDNTLMFEARFESGNL
QKVVKVAEYEYQLTVRPDLFTNKHTQWYYFQVTNMRAGIVYRFTIVNFTKPASLYSRGMR
PLFYSEKEAKAHHIGWQRIGDQIKYYRNNPGQDGRHYFSLTWTFQFPHNKDTCYFAHCYP
YTYTNLQEYLSGINNDPVRSKFCKIRVLCHTLARNMVYILTITTPLKNSDSRKRKAVILT
ARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTFVFKVVPMLNPDGVIVGNYRCSLAGR
DLNRNYTSLLKESFPSVWYTRNMVHRLMEKREVILYCDLHGHSRKENIFMYGCDGSDRSK
TLYLQQRIFPLMLSKNCPDKFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTMEATFCGS
TLGNKRGTHFSTKDLESMGYHFCDSLLDYCDPDRTKYYRCLKELEEMERHITLEKVFEDS
DTPVIDITLDVESSSRGSDSSESIDSLTYLLKLTSQKKHLKTKKERNSTIASHQNARGQE
VYDRGHLLQRHTQSNSDVKDTRPNEPDDYMVDYFRRQLPNQGLAHCKLRLPGSRHSPASA
SRVAGTTGTRHHTWLIFVFLVEMGKKIPLKGTDLYGNCFKVTSLQSPMGKQTSTWTEKTR
IPTEDLHHNLKSKIKECISFQSKKTGINWTDDEKRSYKDKGIVQTQEILQYLLPIVHSTK
NMQTTQIKQLFNPRTNFQIQHQLNPATCRNIKKYSTSWTAPRNHPFVIQGDVMANSSEWV
QSKPHRSLESLSPLKGPKKNKHSQIWAIKNEDIKPLSSKWETASSSFGMDANVLKYKSLQ
AEETNQQSSKHTALHLTKNKDEQANKNDGQPTLYLKFQRES
Function
Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK. May catalyze the hydrolysis of aspartate from the carboxy-terminus of target proteins. Does not show detyrosinase or deglycylase activities from the carboxy-terminus of target proteins; [Isoform 2]: Metallocarboxypeptidase that mediates tubulin deglutamylation.
Reactome Pathway
Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthritis DIST1YEL Definitive Biomarker [1]
Rheumatoid arthritis DISTSB4J Strong Biomarker [2]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [3]
Osteoarthritis DIS05URM moderate Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Cytosolic carboxypeptidase 3 (AGBL3). [5]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Cytosolic carboxypeptidase 3 (AGBL3). [6]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Cytosolic carboxypeptidase 3 (AGBL3). [8]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Cytosolic carboxypeptidase 3 (AGBL3). [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 Cytosolic carboxypeptidase 3 (AGBL3). [7]
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References

1 The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population.Rheumatology (Oxford). 2017 Dec 1;56(12):2229-2236. doi: 10.1093/rheumatology/kex360.
2 The role of synthetic manufactured peptides containing common citrullinated epitopes in rheumatoid arthritis diagnosis.Clin Immunol. 2019 Feb;199:7-11. doi: 10.1016/j.clim.2018.12.004. Epub 2018 Dec 10.
3 A novel bedside test for ACPA: the CCPoint test is moving the laboratory to the rheumatologist's office.Immunol Res. 2017 Feb;65(1):363-368. doi: 10.1007/s12026-016-8846-2.
4 Comparison of second- and third-generation immunoassays for detection of anti-cyclic citrullinated peptide antibodies.Scand J Clin Lab Invest. 2018 Oct;78(6):477-482. doi: 10.1080/00365513.2018.1499957. Epub 2018 Aug 3.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
7 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.
8 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
9 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.