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Protein

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

Gene

PDE3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

Keywordsi

Molecular functionHydrolase
LigandcAMP, cGMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.17 2681
ReactomeiR-HSA-418457 cGMP effects
R-HSA-418555 G alpha (s) signalling events
SABIO-RKiQ14432
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

EuPathDBiHostDB:ENSG00000172572.6
HGNCiHGNC:8778 PDE3A
MIMi123805 gene
neXtProtiNX_Q14432

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 dbSNP:rs794726865EnsemblClinVar.1
Natural variantiVAR_073870445T → N in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726864EnsemblClinVar.1
Natural variantiVAR_073871445T → S in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726864EnsemblClinVar.1
Natural variantiVAR_073872447A → T in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726866EnsemblClinVar.1
Natural variantiVAR_073873447A → V in HTNB; gain of function mutationwith increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726867EnsemblClinVar.1
Natural variantiVAR_073874449G → V in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726868EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5139
MalaCardsiPDE3A
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
Cross-linki1120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14432
MaxQBiQ14432
PaxDbiQ14432
PeptideAtlasiQ14432
PRIDEiQ14432
ProteomicsDBi59987

PTM databases

iPTMnetiQ14432
PhosphoSitePlusiQ14432

Expressioni

Gene expression databases

BgeeiENSG00000172572 Expressed in 170 organ(s), highest expression level in heart right ventricle
CleanExiHS_PDE3A
GenevisibleiQ14432 HS

Organism-specific databases

HPAiHPA014492

Interactioni

Binary interactionsi

Protein-protein interaction databases

BioGridi111165, 28 interactors
DIPiDIP-42197N
IntActiQ14432, 18 interactors
MINTiQ14432
STRINGi9606.ENSP00000351957

Chemistry databases

BindingDBiQ14432

Structurei

3D structure databases

ProteinModelPortaliQ14432
SMRiQ14432
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini674 – 1093PDEasePROSITE-ProRule annotationAdd BLAST420

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
OMAiPNEEETC
OrthoDBiEOG091G0BTI
PhylomeDBiQ14432
TreeFamiTF329631

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

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 → N1 PublicationCorresponds to variant dbSNP:rs12305038Ensembl.1
Natural variantiVAR_073869445T → A in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726865EnsemblClinVar.1
Natural variantiVAR_073870445T → N in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726864EnsemblClinVar.1
Natural variantiVAR_073871445T → S in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726864EnsemblClinVar.1
Natural variantiVAR_073872447A → T in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726866EnsemblClinVar.1
Natural variantiVAR_073873447A → V in HTNB; gain of function mutationwith increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726867EnsemblClinVar.1
Natural variantiVAR_073874449G → V in HTNB; gain of function mutation with increased cAMP-hydrolytic activity. 1 PublicationCorresponds to variant dbSNP:rs794726868EnsemblClinVar.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

Similar proteinsi

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, 28 interactors
DIPiDIP-42197N
IntActiQ14432, 18 interactors
MINTiQ14432
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
ProteomicsDBi59987

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5139
DisGeNETi5139
EuPathDBiHostDB:ENSG00000172572.6
GeneCardsiPDE3A
HGNCiHGNC:8778 PDE3A
HPAiHPA014492
MalaCardsiPDE3A
MIMi112410 phenotype
123805 gene
neXtProtiNX_Q14432
OpenTargetsiENSG00000172572
PharmGKBiPA33126
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEGG Eukaryota
ENOG410XT2V LUCA
GeneTreeiENSGT00760000119066
HOGENOMiHOG000060144
HOVERGENiHBG053541
KOiK19021
OMAiPNEEETC
OrthoDBiEOG091G0BTI
PhylomeDBiQ14432
TreeFamiTF329631

Enzyme and pathway databases

BRENDAi3.1.4.17 2681
ReactomeiR-HSA-418457 cGMP effects
R-HSA-418555 G alpha (s) signalling events
SABIO-RKiQ14432
SIGNORiQ14432

Miscellaneous databases

ChiTaRSiPDE3A human
GenomeRNAii5139
PROiPR:Q14432
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172572 Expressed in 170 organ(s), highest expression level in heart right ventricle
CleanExiHS_PDE3A
GenevisibleiQ14432 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDE3A_HUMAN
AccessioniPrimary (citable) accession number: Q14432
Secondary accession number(s): O60865, Q13348, Q17RD1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 10, 2004
Last modified: September 12, 2018
This is version 171 of the entry and version 3 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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