Protein detail

PDE4A

3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A)

Entry name PDE4A	UniProt ID P27815	EVMP confidence score 0.50
Supporting publications (n) 3	Transmembrane count	Protein classification EnzymesFDA approved drug targetsMetabolic proteinsPredicted intracellular proteins

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information11

Protein Names

3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A)

Protein Class (4)

EnzymesFDA approved drug targetsMetabolic proteinsPredicted intracellular proteins

Protein Function (4)

Predicted intracellular proteins
Enzymes
FDA approved drug targets:Small molecule drugs
ENZYME proteins:Hydrolases

Ensembl

ENSG00000065989

Entrez Gene Symbol

PDE4A

Gene Synonym

DPDE2

Gene Description

Phosphodiesterase 4A

Chromosome

Position

10416773-10469630

Supporting publications (n)

EVMP confidence score

0.50

Fluorescence & Localization2

Tissue Specificparathyroid gland

Function & Pathway8

Protein Function (4)

Predicted intracellular proteins
Enzymes
FDA approved drug targets:Small molecule drugs
ENZYME proteins:Hydrolases

Cellular Component (8)

Molecular Function (5)

Biological Process (3)

KEGG (5)

Reactome (5)

Canonical Pathways (3)

M36 Pid il27 pathway
M196 Pid il23 pathway
M54 Pid il12 2pathway

Mediation Categories (2)

Clinical-translation mediationReceptor-signaling mediation

Relations & Evidence12

Enzyme-Mediated Modification (2)

2 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
PDE4A	MAPKAPK2	P49137	S	152	phosphorylation	SIGNOR	SIGNOR:21323643
PDE4A	PRKACA	P17612	S	145	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper

Ligand-Receptor Signaling (7)

7 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
receptor	receptor	scConnect	No	Yes	No	No	No

Regulatory Interaction Network (1)

1 record.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
MAPK2	P49137	PDE4A	P27815	Yes	No	Yes	SIGNOR_ProtMapperiPTMnetSIGNORProtMapper	SIGNOR:21323643 ProtMapper:21323643

Protein Complex Composition (1)

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	PDE4A	P27815	2	PDB	PDB:3tvxPDB:2qykPDB:3i8v

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
	Mass spectrometry	1	32384937

Sequence, Structure & Domains14

Sequences

Length

886

Mass

98,143

Sequence

MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTDQEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYMLTLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDMVLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLELYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEEISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLTQQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLPSTAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT

Alternative Products

Event=Alternative splicing; Named isoforms=7; Comment=Additional isoforms seem to exist.; Name=1; Synonyms=PDE4A4, PDE4A4B, PDE46; IsoId=P27815-1; Sequence=Displayed; Name=2; Synonyms=TM3, PDE4A11; IsoId=P27815-2; Sequence=VSP_004556; Name=3; Synonyms=PDE4A7, PDE4A6; IsoId=P27815-3; Sequence=VSP_004557; Name=4; Synonyms=PDE4A1, RD1; IsoId=P27815-4; Sequence=VSP_004558; Name=5; Synonyms=PDE4A8A, 2EL; IsoId=P27815-5; Sequence=VSP_004559, VSP_004560, VSP_004561; Name=6; Synonyms=PDE4A10; IsoId=P27815-6; Sequence=VSP_038185; Name=7; Synonyms=PDE4A8; IsoId=P27815-7; Sequence=VSP_038186

Alternative Sequence

1..367; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTDQEELLAQ -> MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ (in isoform 5); 1..261; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHK -> MPLVDFFCETCSKPWLVGWWDQ (in isoform 4); 1..209; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRS -> MCPFPVTTV (in isoform 3); 1..107; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR -> MARPRGLGRIPELQLVAFPVAVAAEDEAFLPEPLAPRAPRRPRSPPSSPVFFASPSPTFRRRLRLLRSCQDLGRQAWAGAG (in isoform 2); 1..107; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR -> MRSGAAPRARPRPPALALPPTGPESLTHFPFSDEDTRRHPPGRSVS (in isoform 6); 1..107; MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR -> MKRSRSALSVAGTGDERSRETPESDRANMLGADLRRPRRRLSSGPGLGWAQPEPSDPGVPLPPRPTTLPLLIPPRISITRAENDS (in isoform 7); 644..657; GFIDYIVHPLWETW -> QARGIDGRAQGGFY (in isoform 5); 658..886; Missing (in isoform 5)

3D Structural Models

Turn

386..388; 455..457; 473..476; 496..498; 521..524; 633..635; 661..665

Helix

362..368; 369..371; 379..385; 390..401; 404..407; 412..424; 435..449; 452..454; 460..472; 482..487; 491..495; 501..512; 513..515; 527..542; 546..548; 549..561; 576..591; 594..596; 599..622; 638..648; 650..660; 666..682

Beta Strand

430..434; 567..569

3D Structure

X-ray crystallography (3)

Domain & Motif Annotations

Compositional Bias

36..46; Low complexity; 51..78; Basic and acidic residues; 93..104; Gly residues; 315..328; Pro residues; 876..886; Gly residues

Domain (FT)

357..686; PDEase

Region

1..128; Disordered; 294..331; Disordered; 682..705; Disordered; 866..886; Disordered

Protein Families (2)

Cyclic nucleotide phosphodiesterase family
PDE4 subfamily

Sequence Similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Clinical Relevance6

Disease Involvement

FDA approved drug targets

Biomarker

Investigative; Terminated; Approved; Phase 2; Discontinued in Phase 3; Phase 1; Phase 3; Discontinued in Phase 2; Discontinued in Phase 1

Drug Targets

FDA approved drug targets

Antibody (3)

CAB017632 HPA043310 HPA076091

Supporting Publications3

PMID	Title	Abstract
37922300	Proteomic profiling of urinary extracellular vesicles differentiates breast cancer patients from healthy women.	No abstract available
38731868	The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.	No abstract available
40784529	Serum-derived exosome proteomics unveils the distinct and adjustable nature of the dampness constitution in traditional Chinese medicine.	No abstract available