Protein detail
PDE4D
3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D)
Entry name PDE4D | UniProt ID | EVMP confidence score 0.63 |
Supporting publications (n) 7 | Transmembrane count | Protein classification Disease related genesEnzymesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted intracellular proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information11
Protein Names
3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D)
Protein Class (6)
Disease related genesEnzymesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted intracellular proteins
Protein Function (6)
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- Enzymes
- ENZYME proteins:Hydrolases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym
DPDE3
Gene Description
Phosphodiesterase 4D
Chromosome
5
Position
58969038-60522120
Supporting publications (n)
7
EVMP confidence score
0.63
Fluorescence & Localization3
Tissue SpecifickidneyCell SpecificCardiomyocytes
Function & Pathway8
Protein Function (6)
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- Enzymes
- ENZYME proteins:Hydrolases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component (9)
Molecular Function (14)
- GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
- GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
- GO:0005246 calcium channel regulator activity
- GO:0005515 protein binding
- GO:0019899 enzyme binding
- GO:0030545 signaling receptor regulator activity
- GO:0030552 cAMP binding
- GO:0031698 beta-2 adrenergic receptor binding
- GO:0044325 transmembrane transporter binding
- GO:0046872 metal ion binding
Page 1 of 2
Biological Process (3)
KEGG (5)
Reactome (8)
- R-hsa-9855142 cellular responses to mechanical stimuli
- R-hsa-8953897 cellular responses to stimuli
- R-hsa-180024 darpp 32 events
- R-hsa-418594 g alpha i signalling events
- R-hsa-418555 g alpha s signalling events
- R-hsa-111885 opioid signalling
- R-hsa-372790 signaling by gpcr
- R-hsa-9860927 turbulent oscillatory disturbed flow shear stress activates signaling by piezo1 and integrins in endothelial cells
Canonical Pathways (3)
- M86 Pid arf6 pathway
- M232 Pid ecadherin stabilization pathway
- M91 Pid tcptp pathway
Mediation Categories (5)
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence35
Enzyme-Mediated Modification (12)
12 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| PDE4D | MAPK1 | P28482 | S | 715 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapper | ProtMapper:10828059SIGNOR:16973330ProtMapper:10022832SIGNOR:10022832SIGNOR:10828059ProtMapper:16973330 |
| PDE4D | MAPK1 | P28482 | S | 579 | phosphorylation | PhosphoSiteSIGNOR | SIGNOR:10828059 |
| PDE4D | MAPK1 | P28482 | S | 413 | phosphorylation | PhosphoSite | |
| PDE4D | MAPK1 | P28482 | S | 490 | phosphorylation | PhosphoSite | |
| PDE4D | MAPK3 | P27361 | S | 715 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapper | ProtMapper:10828059SIGNOR:10828059 |
| PDE4D | MAPK3 | P27361 | S | 579 | phosphorylation | PhosphoSite | |
| PDE4D | MAPK3 | P27361 | S | 651 | phosphorylation | PhosphoSite | |
| PDE4D | PRKACA | P17612 | S | 54 | phosphorylation | HPRDPhosphoSiteKEA | HPRD:8663227HPRD:18212344HPRD:20068231KEA:8663227 |
| PDE4D | PRKACA | P17612 | S | 13 | phosphorylation | PhosphoSiteKEA | KEA:8663227 |
| PDE4D | PRKACA | P17612 | S | 126 | phosphorylation | PhosphoSite |
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Ligand-Receptor Signaling (10)
10 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| apical_cell_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network (4)
4 records.
Protein Complex Composition (8)
8 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| A2ML1L2HGDHNPPAPDE4DIPPM20D1 | A8K2U0P01160Q5VU43Q6GTS8Q9H9P8 | 0:0:0:0:0 | hu.MAP2 | |||
| PDE4DPOMPPSMA1PSMA2PSMA6PSMA7PSMB1PSMB2PSMB3PSMB7PSMB8PSMB9TAP1TAP2UBC | O14818P0CG48P20618P25786P25787P28062P28065P49720P49721P60900Q03518Q03519Q08499Q99436Q9Y244 | 1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC7720 | ||
| CLASP2KIF18BMAPRE1PDE4DIP | O75122Q15691Q5VU43Q86Y91 | 0:0:0:0 | hu.MAP | |||
| ITPKBPDE4BPDE4D | P27987Q07343Q08499 | 0:0:0 | hu.MAP2 | |||
| ITPKBPDE4D | P27987Q08499 | 0:0 | hu.MAP | |||
| PDE4BPDE4D | Q07343Q08499 | 0:0 | hu.MAP2 | |||
| PDE4D | Q08499 | 12 | PDB | PDB:6ftwPDB:6fw3PDB:6imtPDB:1oynPDB:2fm5PDB:3g4lPDB:4w1oPDB:6imrPDB:6imoPDB:7cbqPDB:3iadPDB:7w4yPDB:3g4gPDB:6bojPDB:6imdPDB:9lo7PDB:8wdnPDB:6fe7PDB:6hwoPDB:3sl6PDB:7abjPDB:7xabPDB:5wqaPDB:6imiPDB:3v9bPDB:6im6PDB:6iagPDB:5lboPDB:7f2kPDB:3g4iPDB:6fetPDB:5tkbPDB:7f2lPDB:2pw3PDB:7a8qPDB:1zknPDB:3sl3PDB:7a9vPDB:6kjzPDB:7w4xPDB:4ogbPDB:6f6uPDB:6f8xPDB:7ay6PDB:3sl8PDB:6inmPDB:7yqfPDB:6f8wPDB:7cbjPDB:7b9hPDB:6inkPDB:1xorPDB:6ftaPDB:6imbPDB:3g58PDB:6rcwPDB:7xaaPDB:1ptwPDB:1q9mPDB:6fdiPDB:8ylcPDB:6f8uPDB:7f2mPDB:6akrPDB:7ysxPDB:1y2kPDB:8k4cPDB:6ft0PDB:8w4qPDB:8zq2PDB:1y2cPDB:7abdPDB:5wh6PDB:6zbaPDB:6indPDB:1tbbPDB:8zquPDB:7abePDB:3g4kPDB:3sl5PDB:8wdoPDB:8xxsPDB:6f8vPDB:8k4hPDB:3sl4PDB:4wcuPDB:1xoqPDB:6febPDB:1xonPDB:7aagPDB:1mkdPDB:6ibfPDB:8w4rPDB:6f8rPDB:1y2bPDB:1y2ePDB:6f8tPDB:1y2dPDB:6njhPDB:1xomPDB:5k1iPDB:7xbbPDB:6fdcPDB:2qynPDB:8zq1PDB:6njjPDB:6kk0PDB:8zqwPDB:6njiPDB:1tb7PDB:5k32PDB:2fm0PDB:7ab9PDB:6lrmPDB:5wh5 | ||
| KIF18BMAPRE1PDE4DIPSYBU | Q15691Q5VU43Q86Y91Q9NX95 | 0:0:0:0 | hu.MAP |
Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | Western blottingFlow cytometry | 1 | 38321535 |
Sequence, Structure & Domains14
Sequences
Length
809
Mass
91,115
Sequence
MEAEGSSAPARAGSGEGSDSAGGATLKAPKHLWRHEQHHQYPLRQPQFRLLHPHHHLPPPPPPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRRFDVDNGTSAGRSPLDPMTSPGSGLILQANFVHSQRRESFLYRSDSDYDLSPKSMSRNSSIASDIHGDDLIVTPFAQVLASLRTVRNNFAALTNLQDRAPSKRSPMCNQPSINKATITEEAYQKLASETLEELDWCLDQLETLQTRHSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNTFLDKQHEVEIPSPTQKEKEKKKRPMSQISGVKKLMHSSSLTNSSIPRFGVKTEQEDVLAKELEDVNKWGLHVFRIAELSGNRPLTVIMHTIFQERDLLKTFKIPVDTLITYLMTLEDHYHADVAYHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVGFKLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLQNMVHCADLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCDKHNASVEKSQVGFIDYIVHPLWETWADLVHPDAQDILDTLEDNREWYQSTIPQSPSPAPDDPEEGRQGQTEKFQFELTLEEDGESDTEKDSGSQVEEDTSCSDSKTLCTQDSESTEIPLDEQVEEEAVGEEEESQPEACVIDDRSPDT
Alternative Products
Event=Alternative splicing; Named isoforms=12; Name=4; Synonyms=hPDE4D4; IsoId=Q08499-1; Sequence=Displayed; Name=3; Synonyms=hPDE4D3; IsoId=Q08499-2; Sequence=VSP_004577; Name=10; IsoId=Q08499-3; Sequence=VSP_004578; Name=1; Synonyms=hPDE4D1; IsoId=Q08499-4; Sequence=VSP_004579; Name=2; Synonyms=hPDE4D2; IsoId=Q08499-5; Sequence=VSP_004580; Name=5; Synonyms=hPDE4D5; IsoId=Q08499-6; Sequence=VSP_012384; Name=N3; Synonyms=PDE4DN3; IsoId=Q08499-7; Sequence=VSP_012384, VSP_012391, VSP_012392; Name=6; Synonyms=PDE4D6; IsoId=Q08499-8; Sequence=VSP_012383, VSP_012393; Name=8; Synonyms=PDE4D8; IsoId=Q08499-9; Sequence=VSP_012386, VSP_012389; Name=9; Synonyms=PDE4D9; IsoId=Q08499-10; Sequence=VSP_012385, VSP_012390; Name=7; Synonyms=PDE4D7; IsoId=Q08499-11; Sequence=VSP_012387, VSP_012388; Name=12; IsoId=Q08499-12; Sequence=VSP_012384, VSP_023326, VSP_023327
Alternative Sequence
1..302; Missing (in isoform 2); 1..291; Missing (in isoform 6); 1..269; MEAEGSSAPARAGSGEGSDSAGGATLKAPKHLWRHEQHHQYPLRQPQFRLLHPHHHLPPPPPPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRRFDVDNGTSAGRSPLDPMTSPGSGLILQANFVHSQRRESFLYRSDSDYDLSPKSMSRNSSIASDIHGDDLIVTPFAQVLASLRTVRNNFAALTNLQDRAPSKRSPMCNQPSINKATIT -> MKEQPSCAGTGHPMAGYGRMAPFELASGPVKRLRTESPFPCLFA (in isoform 1); 1..205; Missing (in isoform 10); 1..152; MEAEGSSAPARAGSGEGSDSAGGATLKAPKHLWRHEQHHQYPLRQPQFRLLHPHHHLPPPPPPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MMHVNNFPFRRHSWIC (in isoform 3); 1..152; MEAEGSSAPARAGSGEGSDSAGGATLKAPKHLWRHEQHHQYPLRQPQFRLLHPHHHLPPPPPPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MAQQTSPDTLTVPEVDNPHCPNPWLNEDLVKSLRENLLQHEKSKTARKSVSPKLSPVISPRNSPRLLRRMLLSSNIPKQRRFTVAHTC (in isoform 5, isoform N3 and isoform 12); 1..130; Missing (in isoform 9); 1..122; Missing (in isoform 8); 1..61; Missing (in isoform 7); 62..152; PPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MKRNTCDLLSRSKSASEETLHSSNEEEDPFRGMEPYLVRRLSCRNIQLPPLAFRQLEQADLKSESENIQRPTSLPLKILPLIAITSAESSG (in isoform 7); 123..152; RTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MAFVWDPLGATVPGPSTRAKSRLRFSKSYS (in isoform 8); 131..152; GHRPGLKKSRMSWPSSFQGLRR -> MSIIMKPRSRSTSSLRTAEAVC (in isoform 9); 270..283; EEAYQKLASETLEE -> GSWMELNPYTLLDM (in isoform 12); 270..279; EEAYQKLASE -> GLYNGIIAFL (in isoform N3); 280..809; Missing (in isoform N3); 284..809; Missing (in isoform 12); 292..306; ETLQTRHSVSEMASN -> MPEANYLLSVSWGYI (in isoform 6)
3D Structural Models
Turn
266..271; 484..486; 502..505; 545..547; 550..553; 658..660; 662..664; 690..694; 735..738
Helix
261..265; 275..280; 328..336; 389..397; 398..400; 408..414; 419..430; 433..436; 441..453; 464..478; 481..483; 489..501; 511..516; 520..525; 530..541; 542..544; 556..571; 575..577; 578..590; 595..597; 605..620; 623..625; 628..652; 667..677; 679..689; 695..710; 730..734
Beta Strand
256..259; 272..274; 383..386; 460..463; 598..600
3D Structure
NMR spectroscopy (1); X-ray crystallography (117)
Domain & Motif Annotations
Compositional Bias
58..89; Pro residues; 90..102; Low complexity; 762..773; Polar residues; 779..796; Acidic residues
Domain (FT)
386..715; PDEase
Region
1..107; Disordered; 343..364; Disordered; 710..729; Disordered; 739..809; Disordered
Protein Families (2)
- Cyclic nucleotide phosphodiesterase family
- PDE4 subfamily
Sequence Similarities
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Clinical Relevance9
Disease Involvement (2)
Disease variantFDA approved drug targets
Related Diseases (22)
Acute upper respiratory infectionAllergic/hypersensitivity disorderAlzheimer diseaseAmyloidosisAsthmaAtopic eczemaChoreiform disorderChronic arterial occlusive diseaseChronic obstructive pulmonary diseaseCrohn diseaseMature B-cell leukaemiaMild neurocognitive disorderMood disorderMultiple sclerosisMycosis fungoidesParkinsonismPneumoniaPostoperative inflammationPsoriasisRheumatoid arthritisTonus and reflex abnormalityVitamin deficiency
Biomarker
Investigative; Terminated; Phase 2; Phase 3; Phase 1; Discontinued in Phase 2; Discontinued in Phase 1; Approved
Drug Targets
FDA approved drug targets
Drugs (41)
REVAMILASTOXTRIPHYLLINECILOMILASTTETOMILASTROFLUMILASTIBUDILASTRESVERATROLHT-0712THEOPHYLLINE SODIUM GLYCINATEDENBUFYLLINERONOMILASTBPN14770LIRIMILASTTRANIMILASTCRISABOROLETOFIMILASTGSK-356278ASPIRINFLAVOXATE HYDROCHLORIDELOTAMILASTAPREMILASTROLIPRAMDOVRAMILASTDROTAVERINDIURETICZATOLMILASTMK-0873OGLEMILASTTHEOPHYLLINEGSK-256066PICLAMILASTAMINOPHYLLINEDIFAMILASTETAZOLATEDYPHYLLINEAMLEXANOXENSIFENTRINEPENTOXIFYLLINEQUETIAPINE FUMARATESELECTIVE CYTOKINE INHIBITORY DRUG CC-1088PAPAVERINE
Antibody
Interaction Protein
ENSG00000141480
Interaction Count
1
Interaction Dataset
intact_biogrid
Supporting Publications7
| PMID | Title | Abstract |
|---|---|---|
| 30071318 | Changes in the urinary extracellular vesicle proteome are associated with nephronophthisis-related ciliopathies. | No abstract available |
| 30760538 | Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection. | No abstract available |
| 31320591 | Exosomes regulate neurogenesis and circuit assembly. | No abstract available |
| 31508500 | Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping. | No abstract available |
| 33729255 | A new urinary exosome enrichment method by a combination of ultrafiltration and TiO2 nanoparticles. | No abstract available |
| 38938674 | Gestational age at birth influences protein and RNA content in human milk extracellular vesicles. | No abstract available |
| 39949490 | CRISPR-dCas9 Activation of TSG-6 in MSCs Modulates the Cargo of MSC-Derived Extracellular Vesicles and Attenuates Inflammatory Responses in Human Intervertebral Disc Cells In Vitro. | No abstract available |