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P27815 (PDE4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A

EC=3.1.4.53
Alternative name(s):
DPDE2
PDE46
Gene names
Name:PDE4A
Synonyms:DPDE2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length886 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. Ref.13 Ref.18

Catalytic activity

Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.

Cofactor

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. Ref.18

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-[(3-butoxy-4-methoxyphenyl)-methyl]-2-imidazolidinone (Ro 20-1724), roflumilast and denbufylline. Ref.5 Ref.6 Ref.7

Pathway

Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Subunit structure

Isoform 1 interacts with LYN. Isoform 2 and isoform 6 interact weakly with LYN. Isoform 1, isoform 2 and isoform 6 interact with ARRB2. Ref.5 Ref.6

Subcellular location

Isoform 1: Cytoplasmperinuclear region Ref.5 Ref.6 Ref.7.

Isoform 2: Cytoplasmperinuclear region. Cell projectionruffle membrane Ref.5 Ref.6 Ref.7.

Isoform 4: Membrane; Peripheral membrane protein. Note: Isoform 4 has propensity for association with membranes. Ref.5 Ref.6 Ref.7

Isoform 6: Cytoplasmperinuclear region Ref.5 Ref.6 Ref.7.

Isoform 7: Cytoplasm. Membrane. Note: Predominantly cytoplasmic. Ref.5 Ref.6 Ref.7

Tissue specificity

Isoform 1 is widely expressed. Isoform 2 is abundant in liver, stomach, testis, thyroid and adrenal glands. It is also found in placenta, kidney, pancreas, ovary, uterus, skin, monocytes, mast cells, macrophages, as well as in bronchial smooth muscle. Isoform 6 is expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes. Isoform 7 is expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Isoform 7 is expressed in the brain. Found in specific neuronal subpopulations in cortex, spinal cord and cerebellum (at protein level). Ref.5 Ref.6 Ref.7

Post-translational modification

Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation By similarity. Phosphorylated at Ser-686 and Ser-688 when expressed in S.frugiperda cells. Isoform 2 and isoform 7 are activated by phosphorylation at Ser-119 and Ser-123 respectively by PKA. Ref.6 Ref.7 Ref.13

Proteolytically cleaved by caspase-3. Ref.6

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=4.0 µM for cAMP (isoform 2) Ref.5 Ref.6

KM=3 µM for cAMP (isoform 6)

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandcAMP
Metal-binding
   Molecular functionHydrolase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcAMP catabolic process

Inferred from mutant phenotype PubMed 17704206. Source: UniProtKB

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

regulation of cAMP-mediated signaling

Inferred from electronic annotation. Source: Ensembl

regulation of protein kinase A signaling

Inferred from electronic annotation. Source: Ensembl

sensory perception of smell

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 8940140. Source: ProtInc

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

membrane

Traceable author statement Ref.4. Source: ProtInc

perinuclear region of cytoplasm

Inferred from direct assay Ref.5. Source: UniProtKB

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_function3',5'-cyclic-AMP phosphodiesterase activity

Inferred from direct assay PubMed 17404263. Source: BHF-UCL

cAMP binding

Inferred from genetic interaction Ref.1. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P27815-1)

Also known as: PDE4A4; PDE4A4B; PDE46;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P27815-2)

Also known as: TM3; PDE4A11;

The sequence of this isoform differs from the canonical sequence as follows:
     1-107: MEPPTVPSER...GGAGGGSSRR → MARPRGLGRI...LGRQAWAGAG
Note: Contains a phosphoserine at position 119.
Isoform 3 (identifier: P27815-3)

Also known as: PDE4A7; PDE4A6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-209: MEPPTVPSER...NVPVPSNKRS → MCPFPVTTV
Isoform 4 (identifier: P27815-4)

Also known as: PDE4A1; RD1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-261: MEPPTVPSER...RSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ
Isoform 5 (identifier: P27815-5)

Also known as: PDE4A8A; 2EL;

The sequence of this isoform differs from the canonical sequence as follows:
     1-367: MEPPTVPSER...KTDQEELLAQ → MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ
     644-657: GFIDYIVHPLWETW → QARGIDGRAQGGFY
     658-886: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Probably represents a non-functional splice isoform.
Isoform 6 (identifier: P27815-6)

Also known as: PDE4A10;

The sequence of this isoform differs from the canonical sequence as follows:
     1-107: MEPPTVPSER...GGAGGGSSRR → MRSGAAPRAR...RRHPPGRSVS
Isoform 7 (identifier: P27815-7)

Also known as: PDE4A8;

The sequence of this isoform differs from the canonical sequence as follows:
     1-107: MEPPTVPSER...GGAGGGSSRR → MKRSRSALSV...ISITRAENDS
Note: Contains a phosphoserine at position 123.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 886886cAMP-specific 3',5'-cyclic phosphodiesterase 4A
PRO_0000198806

Regions

Nucleotide binding433 – 4375cAMP By similarity
Region330 – 723394Catalytic

Sites

Active site4331Proton donor By similarity
Metal binding4371Divalent metal cation 1
Metal binding4731Divalent metal cation 1
Metal binding4741Divalent metal cation 1
Metal binding4741Divalent metal cation 2
Metal binding5911Divalent metal cation 1
Binding site4741cAMP By similarity
Binding site5911cAMP By similarity
Binding site6421cAMP By similarity
Site69 – 702Cleavage; by caspase-3
Site5941Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue1521Phosphoserine; by MAPKAPK2 By similarity
Modified residue1651Phosphoserine Ref.16
Modified residue6861Phosphoserine Probable
Modified residue6881Phosphoserine Probable
Cross-link358Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.17

Natural variations

Alternative sequence1 – 367367MEPPT…ELLAQ → MVLPSDQGFKLLGNVLQGPE PYRLLTSGLRLHQ in isoform 5.
VSP_004559
Alternative sequence1 – 261261MEPPT…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 4.
VSP_004558
Alternative sequence1 – 209209MEPPT…SNKRS → MCPFPVTTV in isoform 3.
VSP_004557
Alternative sequence1 – 107107MEPPT…GSSRR → MARPRGLGRIPELQLVAFPV AVAAEDEAFLPEPLAPRAPR RPRSPPSSPVFFASPSPTFR RRLRLLRSCQDLGRQAWAGA G in isoform 2.
VSP_004556
Alternative sequence1 – 107107MEPPT…GSSRR → MRSGAAPRARPRPPALALPP TGPESLTHFPFSDEDTRRHP PGRSVS in isoform 6.
VSP_038185
Alternative sequence1 – 107107MEPPT…GSSRR → MKRSRSALSVAGTGDERSRE TPESDRANMLGADLRRPRRR LSSGPGLGWAQPEPSDPGVP LPPRPTTLPLLIPPRISITR AENDS in isoform 7.
VSP_038186
Alternative sequence644 – 65714GFIDY…LWETW → QARGIDGRAQGGFY in isoform 5.
VSP_004560
Alternative sequence658 – 886229Missing in isoform 5.
VSP_004561
Natural variant7361A → E. Ref.3 Ref.11
Corresponds to variant rs1051738 [ dbSNP | Ensembl ].
VAR_059544
Natural variant8081H → Y.
Corresponds to variant rs2230190 [ dbSNP | Ensembl ].
VAR_059545

Secondary structure

..................................................... 886
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE4A4) (PDE4A4B) (PDE46) [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: 92BB9B98BED711E7

FASTA88698,143
        10         20         30         40         50         60 
MEPPTVPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD SAERAERERQ 

        70         80         90        100        110        120 
PHRPIERADA MDTSDRPGLR TTRMSWPSSF HGTGTGSGGA GGGSSRRFEA ENGPTPSPGR 

       130        140        150        160        170        180 
SPLDSQASPG LVLHAGAATS QRRESFLYRS DSDYDMSPKT MSRNSSVTSE AHAEDLIVTP 

       190        200        210        220        230        240 
FAQVLASLRS VRSNFSLLTN VPVPSNKRSP LGGPTPVCKA TLSEETCQQL ARETLEELDW 

       250        260        270        280        290        300 
CLEQLETMQT YRSVSEMASH KFKRMLNREL THLSEMSRSG NQVSEYISTT FLDKQNEVEI 

       310        320        330        340        350        360 
PSPTMKEREK QQAPRPRPSQ PPPPPVPHLQ PMSQITGLKK LMHSNSLNNS NIPRFGVKTD 

       370        380        390        400        410        420 
QEELLAQELE NLNKWGLNIF CVSDYAGGRS LTCIMYMIFQ ERDLLKKFRI PVDTMVTYML 

       430        440        450        460        470        480 
TLEDHYHADV AYHNSLHAAD VLQSTHVLLA TPALDAVFTD LEILAALFAA AIHDVDHPGV 

       490        500        510        520        530        540 
SNQFLINTNS ELALMYNDES VLENHHLAVG FKLLQEDNCD IFQNLSKRQR QSLRKMVIDM 

       550        560        570        580        590        600 
VLATDMSKHM TLLADLKTMV ETKKVTSSGV LLLDNYSDRI QVLRNMVHCA DLSNPTKPLE 

       610        620        630        640        650        660 
LYRQWTDRIM AEFFQQGDRE RERGMEISPM CDKHTASVEK SQVGFIDYIV HPLWETWADL 

       670        680        690        700        710        720 
VHPDAQEILD TLEDNRDWYY SAIRQSPSPP PEEESRGPGH PPLPDKFQFE LTLEEEEEEE 

       730        740        750        760        770        780 
ISMAQIPCTA QEALTAQGLS GVEEALDATI AWEASPAQES LEVMAQEASL EAELEAVYLT 

       790        800        810        820        830        840 
QQAQSTGSAP VAPDEFSSRE EFVVAVSHSS PSALALQSPL LPAWRTLSVS EHAPGLPGLP 

       850        860        870        880 
STAAEVEAQR EHQAAKRACS ACAGTFGEDT SALPAPGGGG SGGDPT 

« Hide

Isoform 2 (TM3) (PDE4A11) [UniParc].

Checksum: 6A4FC32E8AF7559D
Show »

FASTA86095,236
Isoform 3 (PDE4A7) (PDE4A6) [UniParc].

Checksum: 35F0A712804410AF
Show »

FASTA68676,380
Isoform 4 (PDE4A1) (RD1) [UniParc].

Checksum: 622A0BA91B7AC938
Show »

FASTA64772,222
Isoform 5 (PDE4A8A) (2EL) [UniParc].

Checksum: 14D0EEF3D6CD4BEE
Show »

FASTA32336,706
Isoform 6 (PDE4A10) [UniParc].

Checksum: B50A342801E605FB
Show »

FASTA82591,323
Isoform 7 (PDE4A8) [UniParc].

Checksum: 1AB6019FC85E37E4
Show »

FASTA86495,571

References

« Hide 'large scale' references
[1]"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs."
Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K.
Mol. Cell. Biol. 13:6558-6571(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)."
Sullivan M., Egerton M., Shakur Y., Marquardsen A., Houslay M.D.
Cell. Signal. 6:793-812(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19."
Horton Y.M., Sullivan M., Houslay M.D.
Biochem. J. 308:683-691(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), VARIANT GLU-736.
[4]"Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2."
Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.
Biochem. J. 333:693-703(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
Tissue: Brain.
[5]"Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic AMP-specific phosphodiesterase PDE4A10."
Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E., Sullivan M., Houslay M.D.
Mol. Pharmacol. 59:996-1011(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY, INTERACTION WITH LYN.
Tissue: Brain.
[6]"Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene."
Wallace D.A., Johnston L.A., Huston E., Macmaster D., Houslay T.M., Cheung Y.-F., Campbell L., Millen J.E., Smith R.A., Gall I., Knowles R.G., Sullivan M., Houslay M.D.
Mol. Pharmacol. 67:1920-1934(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHORYLATION AT SER-119 (ISOFORM 2), CLEAVAGE BY CASPASE-3 (ISOFORM 1), INTERACTION WITH LYN AND ARRB2.
[7]"Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change."
Mackenzie K.F., Topping E.C., Bugaj-Gaweda B., Deng C., Cheung Y.-F., Olsen A.E., Stockard C.R., High Mitchell L., Baillie G.S., Grizzle W.E., De Vivo M., Houslay M.D., Wang D., Bolger G.B.
Biochem. J. 411:361-369(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-123 (ISOFORM 7).
[8]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[11]"Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase."
Livi G.P., Kmetz P., McHale M.M., Cieslinski L.B., Sathe G.M., Taylor D.P., Davis R.L., Torphy T.J., Balcarek J.M.
Mol. Cell. Biol. 10:2678-2686(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-886, VARIANT GLU-736.
Tissue: Monocyte.
[12]McLaughlin M.M.
Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[13]"Purification and characterization of the human pde4a catalytic domain (pde4a(330-723)) expressed in sf9 cells."
Lario P.I., Bobechko B., Bateman K., Kelly J., Vrielink A., Huang Z.
Arch. Biochem. Biophys. 394:54-60(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-686 AND SER-688, IDENTIFICATION BY MASS SPECTROMETRY.
[14]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK."
Li X., Vadrevu S., Dunlop A., Day J., Advant N., Troeger J., Klussmann E., Jaffrey E., Hay R.T., Adams D.R., Houslay M.D., Baillie G.S.
Biochem. J. 428:55-65(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-358 BY PIAS4.
[18]"Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors."
Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J., Ke H.
Biochem. J. 408:193-201(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 351-683 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP, FUNCTION, COFACTOR.
[19]"Crystal structure of human PDE4a with 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone."
Cheng R.K.Y., Crawley L., Barker J., Wood M., Felicetti B., Whittaker M.
Submitted (JUL-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 351-683 IN COMPLEX WITH METAL IONS AND INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L20965 mRNA. Translation: AAA03588.1.
S75213 mRNA. Translation: AAB33798.1.
U18087 mRNA. Translation: AAC50458.1.
U18088 mRNA. Translation: AAA98540.1.
AF069491 expand/collapse EMBL AC list , AF069487, AF069489, AF069490 Genomic DNA. Translation: AAC35012.1.
AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35013.1.
AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35014.1.
AF069491 expand/collapse EMBL AC list , AF069488, AF069489, AF069490 Genomic DNA. Translation: AAC35015.1.
U68532 mRNA. Translation: AAC63832.1.
U97584 mRNA. Translation: AAC25679.1.
AF073745 mRNA. Translation: AAD34217.2.
AY618547 mRNA. Translation: AAU82096.1.
AY593872 mRNA. Translation: AAT00628.1.
AC011548 Genomic DNA. No translation available.
AC011529 Genomic DNA. No translation available.
AC011461 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84104.1.
CH471106 Genomic DNA. Translation: EAW84105.1.
CH471106 Genomic DNA. Translation: EAW84108.1.
BC019864 mRNA. Translation: AAH19864.1.
BC038234 mRNA. Translation: AAH38234.1.
M37744 mRNA. Translation: AAA69697.1.
CCDSCCDS12238.1. [P27815-4]
CCDS45961.1. [P27815-1]
CCDS45962.1. [P27815-2]
CCDS45963.1. [P27815-6]
CCDS58649.1. [P27815-7]
PIRA54442.
S55348.
RefSeqNP_001104777.1. NM_001111307.1. [P27815-1]
NP_001104778.1. NM_001111308.1. [P27815-2]
NP_001104779.1. NM_001111309.1. [P27815-6]
NP_001230050.1. NM_001243121.1. [P27815-7]
NP_006193.1. NM_006202.2. [P27815-4]
UniGeneHs.89901.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QYKX-ray2.10A/B351-683[»]
3I8VX-ray2.25A/B351-683[»]
3TVXX-ray2.84A/B351-683[»]
ProteinModelPortalP27815.
SMRP27815. Positions 259-293, 328-710.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111167. 7 interactions.
IntActP27815. 1 interaction.

Chemistry

BindingDBP27815.
ChEMBLCHEMBL2111340.
DrugBankDB01166. Cilostazol.
DB00975. Dipyridamole.
DB00651. Dyphylline.
DB00824. Enprofylline.
DB01088. Iloprost.
DB00235. Milrinone.
DB00806. Pentoxifylline.
DB00692. Phentolamine.
DB00820. Tadalafil.
DB00277. Theophylline.
GuidetoPHARMACOLOGY1300.

PTM databases

PhosphoSiteP27815.

Polymorphism databases

DMDM116242706.

Proteomic databases

MaxQBP27815.
PaxDbP27815.
PRIDEP27815.

Protocols and materials databases

DNASU5141.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293683; ENSP00000293683; ENSG00000065989. [P27815-2]
ENST00000344979; ENSP00000341007; ENSG00000065989. [P27815-4]
ENST00000352831; ENSP00000270474; ENSG00000065989. [P27815-1]
ENST00000380702; ENSP00000370078; ENSG00000065989. [P27815-7]
ENST00000440014; ENSP00000394754; ENSG00000065989. [P27815-6]
ENST00000592685; ENSP00000468507; ENSG00000065989. [P27815-7]
GeneID5141.
KEGGhsa:5141.
UCSCuc002moj.2. human. [P27815-1]
uc002mok.2. human. [P27815-2]
uc002mol.2. human. [P27815-6]
uc002mom.2. human. [P27815-4]
uc002moo.2. human. [P27815-5]
uc021uow.1. human. [P27815-7]

Organism-specific databases

CTD5141.
GeneCardsGC19P010527.
HGNCHGNC:8780. PDE4A.
HPACAB017632.
HPA043310.
MIM600126. gene.
neXtProtNX_P27815.
PharmGKBPA33128.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG122287.
HOVERGENHBG108239.
InParanoidP27815.
KOK01120.
OMAPSPTMKD.
OrthoDBEOG7HQNBC.
PhylomeDBP27815.
TreeFamTF314638.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressP27815.
BgeeP27815.
CleanExHS_PDE4A.
GenevestigatorP27815.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDE4A. human.
EvolutionaryTraceP27815.
GeneWikiPDE4A.
GenomeRNAi5141.
NextBio19824.
PROP27815.
SOURCESearch...

Entry information

Entry namePDE4A_HUMAN
AccessionPrimary (citable) accession number: P27815
Secondary accession number(s): O75522 expand/collapse secondary AC list , O76092, Q16255, Q16691, Q5DM53, Q6PMT2, Q8IVA7, Q8WUQ3, Q9H3H2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM