Details of the Target

General Information of Target

Target ID LDTP06118
Target Name cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (PDE3A)
Gene Name PDE3A
Gene ID 5139
Synonyms
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A; EC 3.1.4.17; Cyclic GMP-inhibited phosphodiesterase A; CGI-PDE A; cGMP-inhibited cAMP phosphodiesterase; cGI-PDE
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAVPGDAARVRDKPVHSGVSQAPTAGRDCHHRADPASPRDSGCRGCWGDLVLQPLRSSRK
LSSALCAGSLSFLLALLVRLVRGEVGCDLEQCKEAAAAEEEEAAPGAEGGVFPGPRGGAP
GGGARLSPWLQPSALLFSLLCAFFWMGLYLLRAGVRLPLAVALLAACCGGEALVQIGLGV
GEDHLLSLPAAGVVLSCLAAATWLVLRLRLGVLMIALTSAVRTVSLISLERFKVAWRPYL
AYLAGVLGILLARYVEQILPQSAEAAPREHLGSQLIAGTKEDIPVFKRRRRSSSVVSAEM
SGCSSKSHRRTSLPCIPREQLMGHSEWDHKRGPRGSQSSGTSITVDIAVMGEAHGLITDL
LADPSLPPNVCTSLRAVSNLLSTQLTFQAIHKPRVNPVTSLSENYTCSDSEESSEKDKLA
IPKRLRRSLPPGLLRRVSSTWTTTTSATGLPTLEPAPVRRDRSTSIKLQEAPSSSPDSWN
NPVMMTLTKSRSFTSSYAISAANHVKAKKQSRPGALAKISPLSSPCSSPLQGTPASSLVS
KISAVQFPESADTTAKQSLGSHRALTYTQSAPDLSPQILTPPVICSSCGRPYSQGNPADE
PLERSGVATRTPSRTDDTAQVTSDYETNNNSDSSDIVQNEDETECLREPLRKASACSTYA
PETMMFLDKPILAPEPLVMDNLDSIMEQLNTWNFPIFDLVENIGRKCGRILSQVSYRLFE
DMGLFEAFKIPIREFMNYFHALEIGYRDIPYHNRIHATDVLHAVWYLTTQPIPGLSTVIN
DHGSTSDSDSDSGFTHGHMGYVFSKTYNVTDDKYGCLSGNIPALELMALYVAAAMHDYDH
PGRTNAFLVATSAPQAVLYNDRSVLENHHAAAAWNLFMSRPEYNFLINLDHVEFKHFRFL
VIEAILATDLKKHFDFVAKFNGKVNDDVGIDWTNENDRLLVCQMCIKLADINGPAKCKEL
HLQWTDGIVNEFYEQGDEEASLGLPISPFMDRSAPQLANLQESFISHIVGPLCNSYDSAG
LMPGKWVEDSDESGDTDDPEEEEEEAPAPNEEETCENNESPKKKTFKRRKIYCQITQHLL
QNHKMWKKVIEEEQRLAGIENQSLDQTPQSHSSEQIQAIKEEEEEKGKPRGEEIPTQKPD
Q
Target Type
Successful
Target Bioclass
Enzyme
Family
Cyclic nucleotide phosphodiesterase family, PDE3 subfamily
Subcellular location
Membrane
Function
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has also activity toward cUMP. Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling.
TTD ID
T88975
Uniprot ID
Q14432
DrugMap ID
TT06AWU
Ensemble ID
ENST00000359062.4
HGNC ID
HGNC:8778
ChEMBL ID
CHEMBL241

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C74(5.08)  LDD3314  [1]
IA-alkyne
 Probe Info  		C315(0.00); C816(0.00)  LDD0162  [2]
IPM
 Probe Info  		C407(0.00); C526(0.00)  LDD0025  [3]
JW-RF-010
 Probe Info  		N.A.  LDD0026  [3]
TFBX
 Probe Info  		C315(0.00); C526(0.00)  LDD0027  [3]
Acrolein
 Probe Info  		C526(0.00); C407(0.00); C1073(0.00)  LDD0217  [4]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [4]
Methacrolein
 Probe Info  		C526(0.00); C315(0.00); C303(0.00)  LDD0218  [4]
HHS-465
 Probe Info  		N.A.  LDD2240  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa C526(0.00); C407(0.00); C1073(0.00); C315(0.00)  LDD0222  [4]
 LDCM0022  KB02 A101D C74(3.10); C526(1.65)  LDD2250  [1]
 LDCM0023  KB03 A101D C526(2.00); C1073(1.79)  LDD2667  [1]
 LDCM0024  KB05 IGR37 C74(5.08)  LDD3314  [1]
 LDCM0109  NEM HeLa N.A.  LDD0232  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (ARFGEF1) . Q9Y6D6
Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (ARFGEF2) . Q9Y6D5

The Drug(s) Related To This Target

Approved
Click To Hide/Show 11 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Aminophylline Small molecular drug D03TYI
Amrinone Small molecular drug DB01427
Anagrelide Small molecular drug D0D1HW
Caffeine Small molecular drug DB00201
Cilostazol Small molecular drug D03VPC
Enoximone Small molecular drug D0E0SW
Levosimendan Small molecular drug DB00922
Milrinone Small molecular drug DB00235
Oxtriphylline Small molecular drug DB01303
Theophylline Small molecular drug DB00277
Vesnarinone Small molecular drug D0L0ZF
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bemoradan Small molecular drug D08HKT
Investigative
Click To Hide/Show 29 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
1,3,9,9a-tetrahydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D07LCE
1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D0N6MR
1,3-dihydro-naphtho[2,3-d]Imidazol-2-one Small molecular drug D0T3UP
1,5-dihydro-imidazo[2,1-b]Quinazolin-2-one Small molecular drug D0TE6A
2-morpholino-7-(2-phenylethynyl)-4h-chromen-4-one Small molecular drug D04BXL
2-morpholino-7-phenyl-4h-chromen-4-one Small molecular drug D0MJ1L
5-methyl-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D0J7NR
6-(2-imidazol-1-yl-vinyl)-1h-quinolin-2-one Small molecular drug D0TZ8C
6-imidazol-1-yl-3,4-dihydro-1h-quinolin-2-one Small molecular drug D04KDB
7-chloro-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D0NI4Z
7-ethoxy-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D0DX3V
7-fluoro-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D09GTN
7-iodo-1,5-dihydro-imidazo[2,1-b]Quinazolin-2-one Small molecular drug D0E3ID
7-methyl-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D05HFD
8-chloro-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D08XKO
8-methyl-1,3-dihydro-imidazo[4,5-b]Quinolin-2-one Small molecular drug D03GAQ
8-methyl-2-morpholino-7-phenoxy-4h-chromen-4-one Small molecular drug D08WIJ
8-methyl-2-morpholino-7-phenyl-4h-chromen-4-one Small molecular drug D07BFF
Benzoylenurea Small molecular drug D06XVV
Ibudilast Small molecular drug DB05266
Isobutylmethylxanthine Small molecular drug D0R6MT
Kuraidin Small molecular drug D06GUJ
Kurarinol Small molecular drug D0W4ZU
Sophoflavescenol Small molecular drug D00QCL
Tetrahydrobenximidazole Small molecular drug D00YPO
Tofisopam Small molecular drug DB08811
Trapidil Small molecular drug DB09283
2-morpholin-4-yl-8-phenylethynyl-chromen-4-one . D0W3RR
6-pyridin-3-yl-3,4-dihydro-1h-quinolin-2-one . D09CPC
Discontinued
Click To Hide/Show 5 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bmy-20844 Small molecular drug D08NXX
Ci-930 Small molecular drug D0BK6B
Emd-53998 Small molecular drug D0Y6HV
Imazodan Small molecular drug D09UMA
Las-31180 Small molecular drug D01OFY

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
4 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
5 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010