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Protein

cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Gene

PDE3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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 regulationi

Inhibited by cGMP.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei752Proton donorBy similarity1
Metal bindingi756Divalent metal cation 1By similarity1
Metal bindingi836Divalent metal cation 1By similarity1
Metal bindingi837Divalent metal cation 1By similarity1
Metal bindingi837Divalent metal cation 2By similarity1
Metal bindingi950Divalent metal cation 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • cAMP catabolic process Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cellular response to cGMP Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: UniProtKB
  • cGMP-mediated signaling Source: UniProtKB
  • diterpenoid metabolic process Source: Ensembl
  • lipid metabolic process Source: ProtInc
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of vascular permeability Source: UniProtKB
  • oocyte maturation Source: Ensembl
  • positive regulation of oocyte development Source: Ensembl
  • positive regulation of vascular permeability Source: UniProtKB
  • regulation of meiotic nuclear division Source: Ensembl
  • response to cAMP Source: Ensembl
  • response to drug Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, cGMP, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS10538-MONOMER.
BRENDAi3.1.4.17. 2681.
ReactomeiR-HSA-418457. cGMP effects.
R-HSA-418555. G alpha (s) signalling events.
SABIO-RKQ14432.
SIGNORiQ14432.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:PDE3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:8778. PDE3A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei61 – 81HelicalSequence analysisAdd BLAST21
Transmembranei130 – 150HelicalSequence analysisAdd BLAST21
Transmembranei160 – 180HelicalSequence analysisAdd BLAST21
Transmembranei185 – 205HelicalSequence analysisAdd BLAST21
Transmembranei210 – 230HelicalSequence analysisAdd BLAST21
Transmembranei232 – 252HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Hypertension and brachydactyly syndrome (HTNB)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals.
See also OMIM:112410
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073869445T → A in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726865dbSNPEnsembl.1
Natural variantiVAR_073870445T → N in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726864dbSNPEnsembl.1
Natural variantiVAR_073871445T → S in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 Publication1
Natural variantiVAR_073872447A → T in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726866dbSNPEnsembl.1
Natural variantiVAR_073873447A → V in HTNB; gain of function mutationwith increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726867dbSNPEnsembl.1
Natural variantiVAR_073874449G → V in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726868dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5139.
MIMi112410. phenotype.
OpenTargetsiENSG00000172572.
PharmGKBiPA33126.

Chemistry databases

ChEMBLiCHEMBL241.
DrugBankiDB01223. Aminophylline.
DB01427. Amrinone.
DB00261. Anagrelide.
DB00201. Caffeine.
DB01166. Cilostazol.
DB04880. Enoximone.
DB05266. Ibudilast.
DB00922. Levosimendan.
DB00235. Milrinone.
DB01303. Oxtriphylline.
DB00277. Theophylline.
DB08811. Tofisopam.
GuidetoPHARMACOLOGYi1298.

Polymorphism and mutation databases

BioMutaiPDE3A.
DMDMi47117888.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001987991 – 1141cGMP-inhibited 3',5'-cyclic phosphodiesterase AAdd BLAST1141

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei312PhosphoserineCombined sources1
Modified residuei492PhosphoserineCombined sources1
Modified residuei520PhosphoserineCombined sources1
Modified residuei524PhosphoserineBy similarity1
Modified residuei1033PhosphoserineBy similarity1
Modified residuei1036PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14432.
MaxQBiQ14432.
PaxDbiQ14432.
PeptideAtlasiQ14432.
PRIDEiQ14432.

PTM databases

iPTMnetiQ14432.
PhosphoSitePlusiQ14432.

Expressioni

Gene expression databases

BgeeiENSG00000172572.
CleanExiHS_PDE3A.
GenevisibleiQ14432. HS.

Organism-specific databases

HPAiHPA014492.

Interactioni

Protein-protein interaction databases

BioGridi111165. 27 interactors.
DIPiDIP-42197N.
IntActiQ14432. 15 interactors.
MINTiMINT-3295914.
STRINGi9606.ENSP00000351957.

Chemistry databases

BindingDBiQ14432.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LRCmodel-A812-1017[»]
ProteinModelPortaliQ14432.
SMRiQ14432.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni728 – 1086CatalyticBy similarityAdd BLAST359

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi95 – 98Poly-Ala4
Compositional biasi99 – 102Poly-Glu4
Compositional biasi288 – 291Poly-Arg4
Compositional biasi440 – 445Poly-Thr6
Compositional biasi870 – 873Poly-Ala4
Compositional biasi1040 – 1045Poly-Glu6
Compositional biasi1121 – 1125Poly-Glu5

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEGG. Eukaryota.
ENOG410XT2V. LUCA.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000060144.
HOVERGENiHBG053541.
KOiK19021.
OMAiLTSPCHS.
OrthoDBiEOG091G0BTI.
PhylomeDBiQ14432.
TreeFamiTF329631.

Family and domain databases

Gene3Di1.10.1300.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14432-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVPGDAARV RDKPVHSGVS QAPTAGRDCH HRADPASPRD SGCRGCWGDL
60 70 80 90 100
VLQPLRSSRK LSSALCAGSL SFLLALLVRL VRGEVGCDLE QCKEAAAAEE
110 120 130 140 150
EEAAPGAEGG VFPGPRGGAP GGGARLSPWL QPSALLFSLL CAFFWMGLYL
160 170 180 190 200
LRAGVRLPLA VALLAACCGG EALVQIGLGV GEDHLLSLPA AGVVLSCLAA
210 220 230 240 250
ATWLVLRLRL GVLMIALTSA VRTVSLISLE RFKVAWRPYL AYLAGVLGIL
260 270 280 290 300
LARYVEQILP QSAEAAPREH LGSQLIAGTK EDIPVFKRRR RSSSVVSAEM
310 320 330 340 350
SGCSSKSHRR TSLPCIPREQ LMGHSEWDHK RGPRGSQSSG TSITVDIAVM
360 370 380 390 400
GEAHGLITDL LADPSLPPNV CTSLRAVSNL LSTQLTFQAI HKPRVNPVTS
410 420 430 440 450
LSENYTCSDS EESSEKDKLA IPKRLRRSLP PGLLRRVSST WTTTTSATGL
460 470 480 490 500
PTLEPAPVRR DRSTSIKLQE APSSSPDSWN NPVMMTLTKS RSFTSSYAIS
510 520 530 540 550
AANHVKAKKQ SRPGALAKIS PLSSPCSSPL QGTPASSLVS KISAVQFPES
560 570 580 590 600
ADTTAKQSLG SHRALTYTQS APDLSPQILT PPVICSSCGR PYSQGNPADE
610 620 630 640 650
PLERSGVATR TPSRTDDTAQ VTSDYETNNN SDSSDIVQNE DETECLREPL
660 670 680 690 700
RKASACSTYA PETMMFLDKP ILAPEPLVMD NLDSIMEQLN TWNFPIFDLV
710 720 730 740 750
ENIGRKCGRI LSQVSYRLFE DMGLFEAFKI PIREFMNYFH ALEIGYRDIP
760 770 780 790 800
YHNRIHATDV LHAVWYLTTQ PIPGLSTVIN DHGSTSDSDS DSGFTHGHMG
810 820 830 840 850
YVFSKTYNVT DDKYGCLSGN IPALELMALY VAAAMHDYDH PGRTNAFLVA
860 870 880 890 900
TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLINLD HVEFKHFRFL
910 920 930 940 950
VIEAILATDL KKHFDFVAKF NGKVNDDVGI DWTNENDRLL VCQMCIKLAD
960 970 980 990 1000
INGPAKCKEL HLQWTDGIVN EFYEQGDEEA SLGLPISPFM DRSAPQLANL
1010 1020 1030 1040 1050
QESFISHIVG PLCNSYDSAG LMPGKWVEDS DESGDTDDPE EEEEEAPAPN
1060 1070 1080 1090 1100
EEETCENNES PKKKTFKRRK IYCQITQHLL QNHKMWKKVI EEEQRLAGIE
1110 1120 1130 1140
NQSLDQTPQS HSSEQIQAIK EEEEEKGKPR GEEIPTQKPD Q
Length:1,141
Mass (Da):124,979
Last modified:May 10, 2004 - v3
Checksum:iE69504130F39EFEA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69S → C in AAB18673 (PubMed:8695850).Curated1
Sequence conflicti110G → A in AAB18673 (PubMed:8695850).Curated1
Sequence conflicti354 – 371HGLIT…PPNVC → TASLPTSWQTLLFHQTCA (PubMed:8695850).CuratedAdd BLAST18
Sequence conflicti354 – 371HGLIT…PPNVC → TASLPTSWQTLLFHQTCA in CAA06304 (PubMed:10421499).CuratedAdd BLAST18

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05954312D → N.1 PublicationCorresponds to variant rs12305038dbSNPEnsembl.1
Natural variantiVAR_073869445T → A in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726865dbSNPEnsembl.1
Natural variantiVAR_073870445T → N in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726864dbSNPEnsembl.1
Natural variantiVAR_073871445T → S in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 Publication1
Natural variantiVAR_073872447A → T in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726866dbSNPEnsembl.1
Natural variantiVAR_073873447A → V in HTNB; gain of function mutationwith increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726867dbSNPEnsembl.1
Natural variantiVAR_073874449G → V in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant rs794726868dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31754.1.
PIRiA44093.
RefSeqiNP_000912.3. NM_000921.4.
UniGeneiHs.386791.
Hs.737522.

Genome annotation databases

EnsembliENST00000359062; ENSP00000351957; ENSG00000172572.
GeneIDi5139.
KEGGihsa:5139.
UCSCiuc001reh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

PDE3 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31754.1.
PIRiA44093.
RefSeqiNP_000912.3. NM_000921.4.
UniGeneiHs.386791.
Hs.737522.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LRCmodel-A812-1017[»]
ProteinModelPortaliQ14432.
SMRiQ14432.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111165. 27 interactors.
DIPiDIP-42197N.
IntActiQ14432. 15 interactors.
MINTiMINT-3295914.
STRINGi9606.ENSP00000351957.

Chemistry databases

BindingDBiQ14432.
ChEMBLiCHEMBL241.
DrugBankiDB01223. Aminophylline.
DB01427. Amrinone.
DB00261. Anagrelide.
DB00201. Caffeine.
DB01166. Cilostazol.
DB04880. Enoximone.
DB05266. Ibudilast.
DB00922. Levosimendan.
DB00235. Milrinone.
DB01303. Oxtriphylline.
DB00277. Theophylline.
DB08811. Tofisopam.
GuidetoPHARMACOLOGYi1298.

PTM databases

iPTMnetiQ14432.
PhosphoSitePlusiQ14432.

Polymorphism and mutation databases

BioMutaiPDE3A.
DMDMi47117888.

Proteomic databases

EPDiQ14432.
MaxQBiQ14432.
PaxDbiQ14432.
PeptideAtlasiQ14432.
PRIDEiQ14432.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359062; ENSP00000351957; ENSG00000172572.
GeneIDi5139.
KEGGihsa:5139.
UCSCiuc001reh.3. human.

Organism-specific databases

CTDi5139.
DisGeNETi5139.
GeneCardsiPDE3A.
HGNCiHGNC:8778. PDE3A.
HPAiHPA014492.
MIMi112410. phenotype.
123805. gene.
neXtProtiNX_Q14432.
OpenTargetsiENSG00000172572.
PharmGKBiPA33126.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEGG. Eukaryota.
ENOG410XT2V. LUCA.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000060144.
HOVERGENiHBG053541.
KOiK19021.
OMAiLTSPCHS.
OrthoDBiEOG091G0BTI.
PhylomeDBiQ14432.
TreeFamiTF329631.

Enzyme and pathway databases

BioCyciZFISH:HS10538-MONOMER.
BRENDAi3.1.4.17. 2681.
ReactomeiR-HSA-418457. cGMP effects.
R-HSA-418555. G alpha (s) signalling events.
SABIO-RKQ14432.
SIGNORiQ14432.

Miscellaneous databases

ChiTaRSiPDE3A. human.
GenomeRNAii5139.
PROiQ14432.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172572.
CleanExiHS_PDE3A.
GenevisibleiQ14432. HS.

Family and domain databases

Gene3Di1.10.1300.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE3A_HUMAN
AccessioniPrimary (citable) accession number: Q14432
Secondary accession number(s): O60865, Q13348, Q17RD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 10, 2004
Last modified: November 2, 2016
This is version 158 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.