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UniProtKB/Swiss-Prot entry P27815


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PDE4A_HUMAN
Primary accession number P27815
Secondary accession numbers O75522 O76092 Q16255 Q16691 Q8WUQ3
Integrated into Swiss-Prot on August 1, 1992
Sequence was last modified on October 17, 2006 (Sequence version 3)
Annotations were last modified on    November 25, 2008 (Entry version 83)
Name and origin of the protein
Protein name cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Synonyms EC 3.1.4.17
DPDE2
PDE46
Gene name
Name: PDE4A
Synonyms: DPDE2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=8413254 [NCBI, ExPASy, EBI, Israel, Japan]
Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K.;
"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.";
Mol. Cell. Biol. 13:6558-6571(1993).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3; 4 AND 5).
TISSUE=Brain;
PubMed=9677330 [NCBI, ExPASy, EBI, Israel, Japan]
Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.;
"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.";
Biochem. J. 333:693-703(1998).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 112-886.
TISSUE=Monocyte;
PubMed=2160582 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase.";
Mol. Cell. Biol. 10:2678-2686(1990).
[4]
SEQUENCE REVISION.
McLaughlin M.M.;
Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5).
PubMed=7772058 [NCBI, ExPASy, EBI, Israel, Japan]
Horton Y.M., Sullivan M., Houslay M.D.;
"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.";
Biochem. J. 308:683-691(1995).
[6]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
DOI=10.1016/0898-6568(94)00039-5; PubMed=7888306 [NCBI, ExPASy, EBI, Israel, Japan]
Sullivan M., Egerton M., Shakur Y., Marquardsen A., Houslay M.D.;
"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).";
Cell. Signal. 6:793-812(1994).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION, PHOSPHORYLATION AT SER-686 AND SER-688, AND MASS SPECTROMETRY.
DOI=10.1006/abbi.2001.2513; PubMed=11566027 [NCBI, ExPASy, EBI, Israel, Japan]
Lario P.I., Bobechko B., Bateman K., Kelly J., Vrielink A., Huang Z.;
"Purification and characterization of the human pde4a catalytic domain (pde4a(330-723)) expressed in sf9 cells.";
Arch. Biochem. Biophys. 394:54-60(2001).
[9]
SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
DOI=10.1186/gb-2004-5-2-r8; PubMed=14759258 [NCBI, ExPASy, EBI, Israel, Japan]
Hillman R.T., Green R.E., Brenner S.E.;
"An unappreciated role for RNA surveillance.";
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L20965; AAA03588.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069491; AAC35012.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069487; AAC35012.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069489; AAC35012.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069490; AAC35012.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069491; AAC35013.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069489; AAC35013.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069490; AAC35013.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069491; AAC35014.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069489; AAC35014.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069490; AAC35014.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069491; AAC35015.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069488; AAC35015.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069489; AAC35015.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069490; AAC35015.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U68532; AAC63832.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U97584; AAC25679.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M37744; AAA69697.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U18087; AAC50458.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U18088; AAA98540.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S75213; AAB33798.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC019864; AAH19864.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A54442; A54442.
S55348; S55348.
RefSeq NP_001104777.1; -.
UniGene Hs.89901
3D structure databases
PDB
2QYK; X-ray; 2.10 A; A/B=351-683.[ExPASy / RCSB / EBI]
PDBsum 2QYK; -.
ModBase P27815.
PTM databases
PhosphoSite P27815; -.
Organism-specific databases
H-InvDB HIX0014746; -.
HGNC HGNC:8780; PDE4A.
GenAtlas PDE4A.
HPA CAB017632; -.
MIM 600126; gene. [NCBI / EBI]
PharmGKB PA33128; -.
GeneCards P27815.
Gene expression databases
ArrayExpress P27815; -.
CleanEx HS_PDE4A; -.
GermOnline ENSG00000065989; Homo sapiens.
Ontologies
GO
GO:0016020; Cellular component: membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005624; Cellular component: membrane fraction (traceable author statement from ProtInc).
GO:0005625; Cellular component: soluble fraction (traceable author statement from ProtInc).
GO:0004115; Molecular function: 3',5'-cyclic-AMP phosphodiesterase activity (traceable author statement from ProtInc).
GO:0007165; Biological process: signal transduction (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR003607; Met-dep_phosphohydro_HD.
IPR002073; PDEase.
Graphical view of domain structure.
Pfam PF00233; PDEase_I; 1.
Pfam graphical view of domain structure.
PRINTS PR00387; PDIESTERASE1.
SMART SM00471; HDc; 1.
SMART graphical view of domain structure.
PROSITE PS00126; PDEASE_I; 1.
BLOCKS P27815.
ProtoNet P27815.
Genome annotation databases
Ensembl ENSG00000065989; Homo sapiens. [Contig view]
GeneID 5141; -.
KEGG hsa:5141; -.
Phylogenomic databases
HOGENOM P27815; -.
HOVERGEN P27815; -.
Other
DrugBank DB01166; Cilostazol.
DB00975; Dipyridamole.
DB00651; Dyphylline.
DB00824; Enprofylline.
DB01088; Iloprost.
DB00235; Milrinone.
DB00806; Pentoxifylline.
DB00692; Phentolamine.
DB00820; Tadalafil.
DB00277; Theophylline.
NextBio 19824; -.
SOURCE PDE4A; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; cAMP; Hydrolase; Membrane; Phosphoprotein.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   886  886     cAMP-specific 3',5'-cyclic phosphodiesterase 4A. PRO_0000198806
REGION   330   723  394     Catalytic. 
MOD_RES   686   686        Phosphoserine (Probable). 
MOD_RES   688   688        Phosphoserine (Probable). 
VAR_SEQ   1   367        MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTP IRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLR TTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKT MSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTN VPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSG NQVSEYISTTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQ PPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD QEELLAQ -> MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ (in isoform 5). VSP_004559
VAR_SEQ   1   261        MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTP IRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLR TTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKT MSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTN VPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW CLEQLETMQTYRSVSEMASHK -> MPLVDFFCETCSKPWLVGWWDQ (in isoform 4). VSP_004558
VAR_SEQ   1   209        MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTP IRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLR TTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKT MSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTN VPVPSNKRS -> MCPFPVTTV (in isoform 3). VSP_004557
VAR_SEQ   1   107        MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTP IRIQQRGYSDSAERAERERQPHRPIERADAMDTSDRPGLR TTRMSWPSSFHGTGTGSGGAGGGSSRR -> MARPRGLGRIPELQLVAFPVAVAAEDEAFLPEPLAPRAPR RPRSPPSSPVFFASPSPTFRRRLRLLRSCQDLGRQA WAGAG (in isoform 2). VSP_004556
VAR_SEQ   644   657        GFIDYIVHPLWETW -> QARGIDGRAQGGFY (in isoform 5). VSP_004560
VAR_SEQ   658   886        Missing (in isoform 5). VSP_004561
CONFLICT   736   736        A -> E (in Ref. 3; AAA69697 and 5; AAC50458). 
Sequence information
Length: 886 AA [This is the length of the unprocessed precursor] Molecular weight: 98143 Da [This is the MW of the unprocessed precursor] CRC64: 92BB9B98BED711E7 [This is a checksum on the sequence]
        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 

P27815 in FASTA format

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BLAST logo BLAST submission on ExPASy/SIB
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Tools Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
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