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Protein

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A

Gene

Pde9a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart. Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (By similarity). In brain, involved in cognitive function, such as learning and long-term memory (PubMed:18674549, PubMed:22070409, PubMed:22328573).By similarity3 Publications

Catalytic activityi

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 Zn2+ ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.By similarity
  • Mg2+By similarityNote: Binds 1 Mg2+ ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.By similarity

Enzyme regulationi

Specifically inhibited by BAY-73-6691 (1-(2-chlorophenyl)-6-((2R)-3,3,3- trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one) (PubMed:18674549). Specifically inhibited by PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) (PubMed:22070409).2 Publications

Pathwayi: 3',5'-cyclic GMP degradation

This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
Proteins known to be involved in this subpathway in this organism are:
  1. High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (Pde9a), cGMP-specific 3',5'-cyclic phosphodiesterase (Pde5a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a)
This subpathway is part of the pathway 3',5'-cyclic GMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei251Proton donorBy similarity1
Metal bindingi255Zinc; via tele nitrogenBy similarity1
Metal bindingi291Zinc; via tele nitrogenBy similarity1
Metal bindingi292MagnesiumBy similarity1
Metal bindingi292ZincBy similarity1
Binding sitei292cGMPBy similarity1
Metal bindingi401ZincBy similarity1
Binding sitei401cGMPBy similarity1
Binding sitei423cGMPBy similarity1
Binding sitei423Inhibitor specific to Pde9aBy similarity1
Binding sitei452InhibitorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi251 – 255cGMPBy similarity5
Nucleotide bindingi451 – 452cGMPBy similarity2

GO - Molecular functioni

  • 3',5'-cyclic-GMP phosphodiesterase activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cGMP, Magnesium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.4.35. 5301.
ReactomeiR-RNO-418457. cGMP effects.
UniPathwayiUPA00763; UER00748.

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9ACurated (EC:3.1.4.35By similarity)
Gene namesi
Name:Pde9aImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi621035. Pde9a.

Subcellular locationi

  • Cell projectionruffle membrane By similarity
  • Cytoplasmperinuclear region By similarity
  • Golgi apparatus By similarity
  • Endoplasmic reticulum By similarity
  • Cell membranesarcolemma By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3638358.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004331571 – 534High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AAdd BLAST534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei318PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8QZV1.
PRIDEiQ8QZV1.

PTM databases

iPTMnetiQ8QZV1.
PhosphoSitePlusiQ8QZV1.

Expressioni

Tissue specificityi

Widely expressed in brain: highly expressed in the basal forebrain, cerebellum and olfactory bulb (PubMed:11698617, PubMed:14501210). Expressed at highest level in cerebellar Purkinje cells (PubMed:14501210).2 Publications

Gene expression databases

BgeeiENSRNOG00000001174.
GenevisibleiQ8QZV1. RN.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001559.

Chemistry databases

BindingDBiQ8QZV1.

Structurei

3D structure databases

ProteinModelPortaliQ8QZV1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 489CatalyticBy similarityAdd BLAST263

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000008058.
HOVERGENiHBG053545.
InParanoidiF1LRG6.
KOiK13761.
OMAiPRAFKIN.
OrthoDBiEOG091G082I.
PhylomeDBiQ8QZV1.
TreeFamiTF314638.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8QZV1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAGSSSYRP KAIYLDIDGR IQKVVFSKYC NSSDIMDLFC IATGLPRNTT
60 70 80 90 100
ISLLTTDDAM VSIDPTMPAN SERTPYKVRP VAVKQVSERE ELVQGVLAQV
110 120 130 140 150
AEQFSRAFKI NELKAEVANH LAMLEKRVEL EGLKVVEIEK CKSDIKKMRE
160 170 180 190 200
ELAARNNRTN CPCKYSFLDN KKLTPRRDVP TYPKYLLSPE TIEALRKPTF
210 220 230 240 250
DVWLWEPNEM LSCLEHMYHD LGLVRDFSIN PITLRRWLLC VHDNYRSNPF
260 270 280 290 300
HNFRHCFCVT QMMYSMVWLC GLQEKFSQMD ILVLMTAAIC HDLDHPGYNN
310 320 330 340 350
TYQINARTEL AVRYNDISPL ENHHCAIAFQ ILARPECNIF ASVPPEGFRQ
360 370 380 390 400
IRQGMITLIL ATDMARHAEI MDSFKEKMEN FDYSNEEHLT LLKMILIKCC
410 420 430 440 450
DISNEVRPME VAEPWVDCLL EEYFMQSDRE KSEGLPVAPF MDRDKVTKAT
460 470 480 490 500
AQIGFIKFVL IPMFETVTKL FPIVEETMLR PLWESREHYE ELKQLDDAMK
510 520 530
ELQKKTENLT SGATENAPEK TRDAKDNEDR SPPN
Length:534
Mass (Da):61,756
Last modified:June 1, 2002 - v1
Checksum:i4AB9382BA2D2CB54
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF372654 mRNA. Translation: AAL99404.1.
AY145898 mRNA. Translation: AAN64274.1.
AABR06100132 Genomic DNA. No translation available.
AABR06100133 Genomic DNA. No translation available.
AABR06100134 Genomic DNA. No translation available.
AABR06100135 Genomic DNA. No translation available.
BC161837 mRNA. Translation: AAI61837.1.
RefSeqiNP_612552.1. NM_138543.1.
XP_008771015.1. XM_008772793.2.
XP_008771016.1. XM_008772794.2.
XP_008771017.1. XM_008772795.2.
UniGeneiRn.20981.

Genome annotation databases

EnsembliENSRNOT00000001559; ENSRNOP00000001559; ENSRNOG00000001174.
GeneIDi191569.
KEGGirno:191569.
UCSCiRGD:621035. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF372654 mRNA. Translation: AAL99404.1.
AY145898 mRNA. Translation: AAN64274.1.
AABR06100132 Genomic DNA. No translation available.
AABR06100133 Genomic DNA. No translation available.
AABR06100134 Genomic DNA. No translation available.
AABR06100135 Genomic DNA. No translation available.
BC161837 mRNA. Translation: AAI61837.1.
RefSeqiNP_612552.1. NM_138543.1.
XP_008771015.1. XM_008772793.2.
XP_008771016.1. XM_008772794.2.
XP_008771017.1. XM_008772795.2.
UniGeneiRn.20981.

3D structure databases

ProteinModelPortaliQ8QZV1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001559.

Chemistry databases

BindingDBiQ8QZV1.
ChEMBLiCHEMBL3638358.

PTM databases

iPTMnetiQ8QZV1.
PhosphoSitePlusiQ8QZV1.

Proteomic databases

PaxDbiQ8QZV1.
PRIDEiQ8QZV1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001559; ENSRNOP00000001559; ENSRNOG00000001174.
GeneIDi191569.
KEGGirno:191569.
UCSCiRGD:621035. rat.

Organism-specific databases

CTDi5152.
RGDi621035. Pde9a.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000008058.
HOVERGENiHBG053545.
InParanoidiF1LRG6.
KOiK13761.
OMAiPRAFKIN.
OrthoDBiEOG091G082I.
PhylomeDBiQ8QZV1.
TreeFamiTF314638.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
BRENDAi3.1.4.35. 5301.
ReactomeiR-RNO-418457. cGMP effects.

Miscellaneous databases

PROiQ8QZV1.

Gene expression databases

BgeeiENSRNOG00000001174.
GenevisibleiQ8QZV1. RN.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE9A_RAT
AccessioniPrimary (citable) accession number: Q8QZV1
Secondary accession number(s): F1LRG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2015
Last sequence update: June 1, 2002
Last modified: November 30, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.