Details of the Target

General Information of Target

Target ID LDTP03403
Target Name 3',5'-cyclic-AMP phosphodiesterase 4A (PDE4A)
Gene Name PDE4A
Gene ID 5141
Synonyms
DPDE2; 3',5'-cyclic-AMP phosphodiesterase 4A; EC 3.1.4.53; DPDE2; PDE46; cAMP-specific phosphodiesterase 4A
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Target Type
Successful
Target Bioclass
Enzyme
Family
Cyclic nucleotide phosphodiesterase family, PDE4 subfamily
Subcellular location
Membrane; Cytoplasm, perinuclear region; Cytoplasm, cytosol; Peripheral membrane protein
Function
Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.; [Isoform 1]: Efficiently hydrolyzes cAMP.; [Isoform 2]: Efficiently hydrolyzes cAMP.; [Isoform 3]: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP.; [Isoform 4]: Efficiently hydrolyzes cAMP.; [Isoform 6]: Efficiently hydrolyzes cAMP.; [Isoform 7]: Efficiently hydrolyzes cAMP.
TTD ID
T61744
Uniprot ID
P27815
DrugMap ID
TTZ97H5
Ensemble ID
ENST00000293683.9
HGNC ID
HGNC:8780
ChEMBL ID
CHEMBL254

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 SNV: p.I65T; p.R696M .
EFO21 SNV: p.E58K .
FTC133 SNV: p.S190G .
HT1080 SNV: p.D517A .
JHH7 SNV: p.G119S .
JURKAT SNV: p.A733V; p.Q758Ter .
KYSE510 SNV: p.P210S .
LNCaP clone FGC SNV: p.A823V .
MCC26 SNV: p.D498V .
MEWO SNV: p.R252C .
MOLT4 SNV: p.R603H .
PF382 SNV: p.Q400H .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info  		C218(10.96)  LDD1705  [1]
IPM
 Probe Info  		N.A.  LDD2156  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0024  KB05 T cell C218(10.96)  LDD1705  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Caspase-6 (CASP6) Peptidase C14A family P55212
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1 (PFKFB1) Phosphoglycerate mutase family P16118
Transmembrane reductase CYB561D2 (CYB561D2) . O14569
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Endophilin-B1 (SH3GLB1) Endophilin family Q9Y371
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Oxidative stress-induced growth inhibitor 1 (OSGIN1) OKL38 family Q9UJX0

The Drug(s) Related To This Target

Approved
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Amrinone Small molecular drug DB01427
Caffeine Small molecular drug DB00201
Crisaborole Small molecular drug DB05219
Dipyridamole Small molecular drug DB00975
Drotaverine Small molecular drug DB06751
Dyphylline Small molecular drug D02PWM
Enprofylline Small molecular drug D09AMZ
Iloprost Small molecular drug DB01088
Oxtriphylline Small molecular drug DB01303
Theophylline Small molecular drug DB00277
Phase 3
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Denbufylline Small molecular drug D01XHG
Sotb07 . D06VFP
Phase 2
Click To Hide/Show 14 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Awd-12-281 Small molecular drug D0F4TV
Cc-1088 Small molecular drug D0U2DH
Ht-0712 Small molecular drug D07OCV
Lirimilast Small molecular drug D0F5IY
Mk-0873 Small molecular drug D0M7CB
Oglemilast Small molecular drug D0L8KJ
Piclamilast Small molecular drug D0Z2FB
Revamilast Small molecular drug D0X0PW
Tofimilast Small molecular drug D09TFB
Tofisopam Small molecular drug DB82TO
An-2898 . D00JED
Gpd-1116 . D01XFZ
Ox-914 . D0RJ1W
Ta-7906 . D02POH
Phase 1
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Gsk-356278 Small molecular drug D0K9DI
Ronomilast Small molecular drug D0O8JW
Ave-8112 . D01WZL
Mem-1414 . D03CWX
Investigative
Click To Hide/Show 48 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(2,5-diphenyl-furan-3-yl)-phenyl-methanone Small molecular drug D0W7BI
(R)-rolipram Small molecular drug D01RUN
(S)-rolipram Small molecular drug D02FZD
1-butyl-3-methyl-3,7-dihydro-purine-2,6-dione Small molecular drug D00JBC
1-methyl-3-propyl-3,7-dihydro-purine-2,6-dione Small molecular drug D00TQR
2,5-bis-(3,4-dimethoxy-phenyl)-furan Small molecular drug D01CAY
2,5-bis-(3-cyclopentyloxy-4-methoxy-phenyl)-furan Small molecular drug D0N2KP
4-(2,5-diphenyl-furan-3-yl)-morpholine Small molecular drug D0J4AT
6-azido-8-(3-iodo-phenyl)-quinoline Small molecular drug D04XRV
6-imidazol-1-ylmethyl-8-phenyl-quinoline Small molecular drug D0L0NY
8-(3-azido-phenyl)-6-iodo-quinoline Small molecular drug D0V8DB
8-(3-azido-phenyl)-6-pyridin-4-ylmethyl-quinoline Small molecular drug D0Z5SB
8-(3-nitro-phenyl)-6-phenyl-[1,7]Naphthyridine Small molecular drug D02NKD
8-(3-nitro-phenyl)-6-pyridin-4-ylmethyl-quinoline Small molecular drug D0K4HG
Benzyl-(2-imidazol-1-yl-quinazolin-4-yl)-amine Small molecular drug D09AUL
Benzyl-(2-phenyl-quinazolin-4-yl)-amine Small molecular drug D0J7GF
Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine Small molecular drug D01TOR
Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine Small molecular drug D0U8YQ
Benzyl-(2-thiophen-2-yl-quinazolin-4-yl)-amine Small molecular drug D02NWF
Ci-1044 Small molecular drug D0DL6J
Ibudilast Small molecular drug DB05266
Isobutylmethylxanthine Small molecular drug D0R6MT
Kf-66490 Small molecular drug D0E5VP
Kuraidin Small molecular drug D06GUJ
Kurarinol Small molecular drug D0W4ZU
L-454560 Small molecular drug D0JD4C
L-791943 Small molecular drug D0V1IM
L-869298 Small molecular drug D0W7WV
Nitraquazone Small molecular drug D0V5BX
Rolipram Small molecular drug D0T5PO
Rolipram Small molecular drug DB01954
Rs-14491 Small molecular drug D0O3BL
Rs-25344 Small molecular drug D0P2HX
Sophoflavescenol Small molecular drug D00QCL
Trapidil Small molecular drug DB09283
Ucb-101333-3 Small molecular drug D02ZPV
(4r)-4-(3-butoxy-4-methoxybenzyl)Imidazolidin-2-one . DB06842
4-[8-(3-nitrophenyl)-17-naphthyridin-6-yl]Benzoic Acid . DB08299
Al-59640 . D04BMR
Asp-3258 . D0N7HS
Cd-160130 . D0U4SS
Ch-3697 . D05YEL
Chf-5480 . D0K9PS
Nis-62949 . D0Y3PP
Ocid-2987 . D0S6MA
Propentofylline . DB06479
Tas-203 . D0S1HX
Zl-n-91 . D04JNC
Discontinued
Click To Hide/Show 16 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cdp840 Small molecular drug D0UG4T
Ci-1018 Small molecular drug D00DBE
Cilomilast Small molecular drug D02EMR
D-22888 Small molecular drug D0R1QJ
D-4418 Small molecular drug D0K1OA
Gsk256066 Small molecular drug D0U7PS
Sch-351591 Small molecular drug D01FXD
Torbafylline Small molecular drug D0F7TV
Ym-976 Small molecular drug D0C7JT
Daxalipram . D0I0GM
Gw-3600 . D01QUF
Kw-4490 . D03ZVD
Las-37779 . D0V2CN
Nik-616 . D07UHY
Tjn-598 . D01OUA
V-11294a . D08SNX

References

1 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
2 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019