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Reviewed, UniProtKB/Swiss-Prot Q14432 (PDE3A_HUMAN)

Last modified January 19, 2010. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    cGMP-inhibited 3',5'-cyclic phosphodiesterase A
    EC=3.1.4.17
Alternative name(s):
    Cyclic GMP-inhibited phosphodiesterase A
      Short name=CGI-PDE A
Gene names
Name: PDE3A
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1141 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes By similarity.

Catalytic activity

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 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 By similarity.

Enzyme regulation

Inhibited by cGMP.

Subcellular location

Membrane; Multi-pass membrane protein Potential.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   LigandMetal-binding
cAMP
cGMP
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processlipid metabolic process

Traceable author statement. Source: ProtInc

signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular componentextrinsic to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functioncGMP-inhibited cyclic-nucleotide phosphodiesterase activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11411141cGMP-inhibited 3',5'-cyclic phosphodiesterase A
PRO_0000198799

Regions

Transmembrane61 – 8121 Potential
Transmembrane130 – 15021 Potential
Transmembrane160 – 18021 Potential
Transmembrane185 – 20521 Potential
Transmembrane210 – 23021 Potential
Transmembrane232 – 25221 Potential
Region728 – 1086359Catalytic By similarity
Compositional bias95 – 984Poly-Ala
Compositional bias99 – 1024Poly-Glu
Compositional bias288 – 2914Poly-Arg
Compositional bias440 – 4456Poly-Thr
Compositional bias870 – 8734Poly-Ala
Compositional bias1040 – 10456Poly-Glu
Compositional bias1121 – 11255Poly-Glu

Sites

Active site7521Proton donor By similarity
Metal binding7561Divalent metal cation 1 By similarity
Metal binding8361Divalent metal cation 1 By similarity
Metal binding8371Divalent metal cation 1 By similarity
Metal binding8371Divalent metal cation 2 By similarity
Metal binding9501Divalent metal cation 1 By similarity

Amino acid modifications

Modified residue3121Phosphoserine Ref.8 Ref.10
Modified residue4281Phosphoserine Ref.10 Ref.7
Modified residue4401Phosphothreonine Ref.9
Modified residue4951Phosphoserine By similarity

Natural variations

Natural variant121D → N: dbSNP rs12305038. Ref.3
VAR_059543

Experimental info

Sequence conflict691S → C in AAB18673. Ref.3
Sequence conflict1101G → A in AAB18673. Ref.3
Sequence conflict354 – 37118HGLIT…PPNVC → TASLPTSWQTLLFHQTCA Ref.3
Sequence conflict354 – 37118HGLIT…PPNVC → TASLPTSWQTLLFHQTCA Ref.4

Secondary structure

............................... 1141
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14432-1 [UniParc].

Last modified May 10, 2004. Version 3.
Checksum: E69504130F39EFEA

FASTA1,141124,979
        10         20         30         40         50         60 
MAVPGDAARV RDKPVHSGVS QAPTAGRDCH HRADPASPRD SGCRGCWGDL VLQPLRSSRK 

        70         80         90        100        110        120 
LSSALCAGSL SFLLALLVRL VRGEVGCDLE QCKEAAAAEE EEAAPGAEGG VFPGPRGGAP 

       130        140        150        160        170        180 
GGGARLSPWL QPSALLFSLL CAFFWMGLYL LRAGVRLPLA VALLAACCGG EALVQIGLGV 

       190        200        210        220        230        240 
GEDHLLSLPA AGVVLSCLAA ATWLVLRLRL GVLMIALTSA VRTVSLISLE RFKVAWRPYL 

       250        260        270        280        290        300 
AYLAGVLGIL LARYVEQILP QSAEAAPREH LGSQLIAGTK EDIPVFKRRR RSSSVVSAEM 

       310        320        330        340        350        360 
SGCSSKSHRR TSLPCIPREQ LMGHSEWDHK RGPRGSQSSG TSITVDIAVM GEAHGLITDL 

       370        380        390        400        410        420 
LADPSLPPNV CTSLRAVSNL LSTQLTFQAI HKPRVNPVTS LSENYTCSDS EESSEKDKLA 

       430        440        450        460        470        480 
IPKRLRRSLP PGLLRRVSST WTTTTSATGL PTLEPAPVRR DRSTSIKLQE APSSSPDSWN 

       490        500        510        520        530        540 
NPVMMTLTKS RSFTSSYAIS AANHVKAKKQ SRPGALAKIS PLSSPCSSPL QGTPASSLVS 

       550        560        570        580        590        600 
KISAVQFPES ADTTAKQSLG SHRALTYTQS APDLSPQILT PPVICSSCGR PYSQGNPADE 

       610        620        630        640        650        660 
PLERSGVATR TPSRTDDTAQ VTSDYETNNN SDSSDIVQNE DETECLREPL RKASACSTYA 

       670        680        690        700        710        720 
PETMMFLDKP ILAPEPLVMD NLDSIMEQLN TWNFPIFDLV ENIGRKCGRI LSQVSYRLFE 

       730        740        750        760        770        780 
DMGLFEAFKI PIREFMNYFH ALEIGYRDIP YHNRIHATDV LHAVWYLTTQ PIPGLSTVIN 

       790        800        810        820        830        840 
DHGSTSDSDS DSGFTHGHMG YVFSKTYNVT DDKYGCLSGN IPALELMALY VAAAMHDYDH 

       850        860        870        880        890        900 
PGRTNAFLVA TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLINLD HVEFKHFRFL 

       910        920        930        940        950        960 
VIEAILATDL KKHFDFVAKF NGKVNDDVGI DWTNENDRLL VCQMCIKLAD INGPAKCKEL 

       970        980        990       1000       1010       1020 
HLQWTDGIVN EFYEQGDEEA SLGLPISPFM DRSAPQLANL QESFISHIVG PLCNSYDSAG 

      1030       1040       1050       1060       1070       1080 
LMPGKWVEDS DESGDTDDPE EEEEEAPAPN EEETCENNES PKKKTFKRRK IYCQITQHLL 

      1090       1100       1110       1120       1130       1140 
QNHKMWKKVI EEEQRLAGIE NQSLDQTPQS HSSEQIQAIK EEEEEKGKPR GEEIPTQKPD 


Q 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase."
Meacci E., Taira M., Moos M. Jr., Smith C.J., Movsesian M.A., Degerman E., Belfrage P., Manganiello V.
Proc. Natl. Acad. Sci. U.S.A. 89:3721-3725(1992) [PubMed: 1315035] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Myocardium.
[2]Liu H., Manganiello V.
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 12; 63-64 AND 354-371.
[3]"Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis."
Cheung P.P., Xu H., McLaughlin M.M., Ghazaleh F.A., Livi G.P., Colman R.W.
Blood 88:1321-1329(1996) [PubMed: 8695850] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-12.
Tissue: Blood.
[4]"Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum."
Kuthe A., Eckel H., Stief C.G., Uckert S., Forssmann W.-G., Jonas U., Maegert H.-J.
Chem. Biol. Interact. 119:593-598(1999) [PubMed: 10421499] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Penis.
[5]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[6]"Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase."
Degerman E., Moos M. Jr., Rascon A., Vasta V., Meacci E., Smith C.J., Lindgren S., Andersson K.-E., Belfrage P., Manganiello V.
Biochim. Biophys. Acta 1205:189-198(1994) [PubMed: 8155697] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[7]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY.
Tissue: Epithelium.
[8]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, MASS SPECTROMETRY.
Tissue: Platelet.
[9]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-440, MASS SPECTROMETRY.
[10]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312 AND SER-428, MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Wikipedia

PDE3 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M91667 mRNA. Translation: AAA35912.2.
U36798 mRNA. Translation: AAB18673.1.
AJ005036 mRNA. Translation: CAA06304.1.
BC117369 mRNA. Translation: AAI17370.1.
BC117371 mRNA. Translation: AAI17372.1.
IPIIPI00291205.
PIRA44093.
RefSeqNP_000912.3.
UniGeneHs.591150

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LRCmodel-A812-1017[»]
SMRQ14432. Positions 677-1087.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ14432.

PTM databases

PhosphoSiteQ14432.

Proteomic databases

PRIDEQ14432.

Genome annotation databases

EnsemblENST00000359062; ENSP00000351957; ENSG00000172572; Homo sapiens. [Genome view]
GeneID5139.
KEGGhsa:5139.
UCSCuc001reh.1. human.

Organism-specific databases

CTD5139.
GeneCardsGC12P020413.
HGNCHGNC:8778. PDE3A.
HPAHPA014492.
MIM123805. gene.
PharmGKBPA33126.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG12959.
HOGENOMHBG712991.
HOVERGENQ14432.
InParanoidQ14432.
OMAYSQGNPA.
OrthoDBEOG91NX56.
PhylomeDBQ14432.

Enzyme and pathway databases

BRENDA3.1.4.17. 247.
ReactomeREACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpressQ14432.
BgeeQ14432.
CleanExHS_PDE3A.
GenevestigatorQ14432.
GermOnlineENSG00000172572. Homo sapiens.

Family and domain databases

InterProIPR003607. Metal-dep_PHydrolase_HD_dom.
IPR002073. PDEase.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01223. Aminophylline.
DB01427. Amrinone.
DB00261. Anagrelide.
DB01166. Cilostazol.
DB04880. Enoximone.
DB00235. Milrinone.
DB00277. Theophylline.
NextBio19816.
SOURCESearch...

Entry information

Entry namePDE3A_HUMAN
AccessionPrimary (citable) accession number: Q14432
Secondary accession number(s): O60865, Q13348, Q17RD1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 10, 2004
Last modified: January 19, 2010
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents