Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT74EK7Z)

DOT Name cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)
Synonyms EC 3.1.4.17
Gene Name PDE10A
Related Disease
Infantile-onset generalized dyskinesia with orofacial involvement ( )
Obsolete dyskinesia, limb and orofacial, infantile-onset ( )
Striatal degeneration, autosomal dominant 2 ( )
Childhood-onset benign chorea with striatal involvement ( )
UniProt ID
PDE10_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2OUN ; 2OUP ; 2OUQ ; 2OUR ; 2OUS ; 2OUU ; 2OUV ; 2OUY ; 2WEY ; 2Y0J ; 2ZMF ; 3SN7 ; 3SNI ; 3SNL ; 3UI7 ; 3UUO ; 3WI2 ; 3WS8 ; 3WS9 ; 3WYK ; 3WYL ; 3WYM ; 4AEL ; 4AJD ; 4AJF ; 4AJG ; 4AJM ; 4BBX ; 4DDL ; 4DFF ; 4FCB ; 4FCD ; 4HEU ; 4HF4 ; 4LKQ ; 4LLJ ; 4LLK ; 4LLP ; 4LLX ; 4LM0 ; 4LM1 ; 4LM2 ; 4LM3 ; 4LM4 ; 4MRW ; 4MRZ ; 4MS0 ; 4MSA ; 4MSC ; 4MSE ; 4MSH ; 4MSN ; 4MUW ; 4MVH ; 4P0N ; 4P1R ; 4PHW ; 4TPM ; 4TPP ; 4WN1 ; 4XY2 ; 4YQH ; 4YS7 ; 4ZO5 ; 5AXP ; 5AXQ ; 5B4K ; 5B4L ; 5C1W ; 5C28 ; 5C29 ; 5C2A ; 5C2E ; 5C2H ; 5DH4 ; 5DH5 ; 5EDE ; 5EDG ; 5EDH ; 5EDI ; 5I2R ; 5K9R ; 5SDU ; 5SDV ; 5SDW ; 5SDX ; 5SDY ; 5SDZ ; 5SE0 ; 5SE1 ; 5SE2 ; 5SE3 ; 5SE4 ; 5SE5 ; 5SE6 ; 5SE7 ; 5SE8 ; 5SE9 ; 5SEA ; 5SEB ; 5SEC ; 5SED ; 5SEE ; 5SEF ; 5SEG ; 5SEH ; 5SEI ; 5SEJ ; 5SEK ; 5SEL ; 5SEM ; 5SEN ; 5SEO ; 5SEP ; 5SEQ ; 5SER ; 5SES ; 5SET ; 5SEU ; 5SEV ; 5SEW ; 5SEX ; 5SEY ; 5SEZ ; 5SF0 ; 5SF1 ; 5SF2 ; 5SF3 ; 5SF4 ; 5SF5 ; 5SF6 ; 5SF7 ; 5SF8 ; 5SF9 ; 5SFA ; 5SFB ; 5SFC ; 5SFD ; 5SFE ; 5SFF ; 5SFG ; 5SFH ; 5SFI ; 5SFJ ; 5SFK ; 5SFL ; 5SFM ; 5SFN ; 5SFO ; 5SFP ; 5SFQ ; 5SFR ; 5SFS ; 5SFT ; 5SFU ; 5SFV ; 5SFW ; 5SFX ; 5SFY ; 5SFZ ; 5SG0 ; 5SG1 ; 5SG2 ; 5SG3 ; 5SG4 ; 5SG5 ; 5SG6 ; 5SG7 ; 5SG8 ; 5SG9 ; 5SGB ; 5SGC ; 5SGD ; 5SGE ; 5SGF ; 5SGG ; 5SGH ; 5SGI ; 5SGJ ; 5SGK ; 5SGL ; 5SGM ; 5SGN ; 5SGO ; 5SGP ; 5SGQ ; 5SGR ; 5SGS ; 5SGT ; 5SGU ; 5SGV ; 5SGW ; 5SGX ; 5SGY ; 5SGZ ; 5SH0 ; 5SH1 ; 5SH2 ; 5SH3 ; 5SH4 ; 5SH5 ; 5SH6 ; 5SH7 ; 5SH8 ; 5SH9 ; 5SHA ; 5SHB ; 5SHC ; 5SHD ; 5SHE ; 5SHF ; 5SHG ; 5SHH ; 5SHI ; 5SHJ ; 5SHK ; 5SHL ; 5SHM ; 5SHN ; 5SHO ; 5SHP ; 5SHQ ; 5SHR ; 5SHS ; 5SHT ; 5SHU ; 5SHV ; 5SHW ; 5SHX ; 5SHY ; 5SHZ ; 5SI0 ; 5SI1 ; 5SI2 ; 5SI3 ; 5SI4 ; 5SI5 ; 5SI6 ; 5SI7 ; 5SI8 ; 5SI9 ; 5SIA ; 5SIB ; 5SID ; 5SIE ; 5SIF ; 5SIG ; 5SIH ; 5SII ; 5SIJ ; 5SIK ; 5SIL ; 5SIM ; 5SIN ; 5SIO ; 5SIP ; 5SIQ ; 5SIR ; 5SIS ; 5SIT ; 5SIU ; 5SIV ; 5SIW ; 5SIX ; 5SIY ; 5SIZ ; 5SJ0 ; 5SJ1 ; 5SJ2 ; 5SJ3 ; 5SJ4 ; 5SJ5 ; 5SJ6 ; 5SJ7 ; 5SJ8 ; 5SJ9 ; 5SJA ; 5SJB ; 5SJC ; 5SJD ; 5SJE ; 5SJF ; 5SJG ; 5SJH ; 5SJI ; 5SJJ ; 5SJK ; 5SJL ; 5SJM ; 5SJN ; 5SJO ; 5SJP ; 5SJQ ; 5SJR ; 5SJS ; 5SJT ; 5SJU ; 5SJV ; 5SJW ; 5SJX ; 5SJY ; 5SJZ ; 5SK0 ; 5SK1 ; 5SK2 ; 5SK3 ; 5SK4 ; 5SK5 ; 5SK6 ; 5SK7 ; 5SK8 ; 5SK9 ; 5SKA ; 5SKB ; 5SKC ; 5SKD ; 5SKE ; 5SKF ; 5SKG ; 5SKH ; 5SKI ; 5SKJ ; 5SKK ; 5SKL ; 5SKM ; 5SKN ; 5SKO ; 5SKP ; 5SKQ ; 5SKR ; 5SKS ; 5SKT ; 5SKU ; 5SKV ; 5UWF ; 5XUI ; 5XUJ ; 5ZNL ; 6IJH ; 6IJI ; 6KDX ; 6KDZ ; 6KE0 ; 6KO0 ; 6KO1 ; 6KZE ; 6MSA ; 6MSC ; 7BPI ; 7QPF ; 7QPM ; 7QPQ ; 7QPV ; 7QQ4 ; 8DI4
EC Number
3.1.4.17
Pfam ID
PF01590 ; PF00233
Sequence
MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAE
RAAPPRPPLSSAGRPSPAGGPGALSARGGGCGWVAARAPLALAFSSRVPSSSPSFFYFWP
PPPPPPPSFLPSSSAFHLPVRLPGREGAAAAAAAGGGGDAGGGGGGGQEAAPLSVPTSSS
HRGGGGSGGGRRRLFLSPALQGLLLPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGG
GGQTPRRPQGASFALAAAAALLFGSDMEDGPSNNASCFRRLTECFLSPSLTDEKVKAYLS
LHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAPKEVSRYQDTNMQGVVYELNSYIEQ
RLDTGGDNQLLLYELSSIIKIATKADGFALYFLGECNNSLCIFTPPGIKEGKPRLIPAGP
ITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLESGTRIQSVLCLPIVTAIGDLIGIL
ELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVCRGLAKQTELNDFLLDVSKTYFDNI
VAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELYSDLFDIGEEKEGKPVFKKTKEIRF
SIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYTGYTTRNILCMPIVSRGSVIGVVQM
VNKISGSAFSKTDENNFKMFAVFCALALHCANMYHRIRHSECIYRVTMEKLSYHSICTSE
EWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMS
VKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSY
LQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNIFSTLSSSEYEQVLEIIRKAIIATD
LALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPVTKLTANDIYA
EFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKA
CRDNLSQWEKVIRGEETATWISSPSVAQKAAASED
Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition.
Tissue Specificity Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
cAMP sig.ling pathway (hsa04024 )
Morphine addiction (hsa05032 )
Reactome Pathway
G alpha (s) signalling events (R-HSA-418555 )
cGMP effects (R-HSA-418457 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Infantile-onset generalized dyskinesia with orofacial involvement DIS85278 Strong Autosomal recessive [1]
Obsolete dyskinesia, limb and orofacial, infantile-onset DISCW72D Strong Autosomal recessive [2]
Striatal degeneration, autosomal dominant 2 DISBIK77 Strong Autosomal dominant [2]
Childhood-onset benign chorea with striatal involvement DISIP0T0 Supportive Autosomal dominant [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Biotransformations of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
[3H]cAMP DMZRQU7 Investigative cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A) increases the hydrolysis of [3H]cAMP. [11]
Cyclic guanosine monophosphate DMOU93V Investigative cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A) increases the hydrolysis of Cyclic guanosine monophosphate. [11]
------------------------------------------------------------------------------------
10 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 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [8]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [8]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [8]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [8]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A). [9]
------------------------------------------------------------------------------------

References

1 Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy. Am J Hum Genet. 2016 Apr 7;98(4):735-43. doi: 10.1016/j.ajhg.2016.03.015.
2 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
3 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
4 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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 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.
10 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
11 Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem. 1999 Jun 25;274(26):18438-45. doi: 10.1074/jbc.274.26.18438.