Names & Taxonomy

Uniprot ID:
P27815
Entry Name:
PDE4A_HUMAN
Status:
reviewed
Protein Names:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46)
Gene Names:
PDE4A DPDE2
Gene Names Primary:
PDE4A
Organism:
Homo sapiens (Human)

Structure

Length:
886
Sequence:
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTDQEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYMLTLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDMVLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLELYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEEISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLTQQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLPSTAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Cytoplasm, perinuclear region.; Isoform 2: Cytoplasm, perinuclear region. Cell projection, ruffle membrane.; Isoform 4: Membrane; Peripheral membrane protein. Note=Isoform 4 has propensity for association with membranes.; Isoform 6: Cytoplasm, perinuclear region.; Isoform 7: Cytoplasm. Membrane. Note=Predominantly cytoplasmic.

Function

Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Pathway:
Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Catalytic Activity:
Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate.
Cofactor:
COFACTOR: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.0 uM for cAMP (isoform 2)
Enzyme Regulation:
ENZYME REGULATION: Isoform 1, isoform 2, isoform 6 and isoform 7 are inhibited by rolipram and cilomilast. Isoform 1, isoform 2 and isoform 6 are inhibited by 4--2-imidazolidinone (Ro 20-1724), roflumilast and denbufylline.
Active Site:
ACT_SITE 433 433 Proton donor.
Cross Reference Drug Bank:
DB05676 DB00201 DB00975 DB06751 DB00651 DB00824 DB05266 DB01088 DB00920 DB01303 DB00806 DB01656 DB00277 DB08811
Gene Ontology Go:
cytosol
membrane
perinuclear region of cytoplasm
ruffle membrane
3',5'-cyclic-AMP phosphodiesterase activity
cAMP binding
metal ion binding
cAMP catabolic process
cellular response to drug
regulation of cAMP-mediated signaling
regulation of protein kinase A signaling
sensory perception of smell
signal transduction
Gene Ontology Biological Process:
cAMP catabolic process
cellular response to drug
regulation of cAMP-mediated signaling
regulation of protein kinase A signaling
sensory perception of smell
signal transduction
Gene Ontology Molecular Function:
3',5'-cyclic-AMP phosphodiesterase activity
cAMP binding
metal ion binding
Gene Ontology Cellular Component:
cytosol
membrane
perinuclear region of cytoplasm
ruffle membrane
Keywords:
3D-structure
Alternative splicing
Cell membrane
Cell projection
Complete proteome
Cytoplasm
Hydrolase
Isopeptide bond
Membrane
Metal-binding
Phosphoprotein
Polymorphism
Reference proteome
Ubl conjugation
cAMP

Publication

PubMed ID:
8413254 7888306 7772058 9677330 11306681 15738310 18095939 15057824 15489334 2160582 11566027 14759258 18669648 19690332 20196770 17727341