PDE2A phosphodiesterase 2A, cGMP-stimulated [Homo sapiens] - Gene

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Summary

Official Symbol: PDE2Aprovided by HGNC
Official Full Name: phosphodiesterase 2A, cGMP-stimulatedprovided by HGNC
Primary source: HGNC:8777
See related: Ensembl:ENSG00000186642; HPRD:04041; MIM:602658; Vega:OTTHUMG00000102045
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PDE2A1; PED2A4; cGSPDE; CGS-PDE

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Genomic context

Location :: 11q13.4

Sequence :: Chromosome: 11; NC_000011.9 (72287185..72385494, complement)

See PDE2A in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

found in smooth muscle wall of blood vessels transversing the clitoral supepithelial and stromal space
Title: Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5).
Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design
Title: Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design.
the phosphodiesterase 2A isoform localized to mitochondria regulates respiration
Title: A phosphodiesterase 2A isoform localized to mitochondria regulates respiration.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Poor replication of candidate genes for major depressive disorder using genome-wide association data.
report the X-ray crystal structures of a PDE protein that includes both catalytic and regulatory domains, namely, PDE2A containing the N-terminal GAF domains and the catalytic domain.
Title: Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct.
Phosphodiesterase 2 mediates redox-sensitive endothelial cell proliferation and angiogenesis by thrombin via Rac1 and NADPH oxidase 2.
Title: Phosphodiesterase 2 mediates redox-sensitive endothelial cell proliferation and angiogenesis by thrombin via Rac1 and NADPH oxidase 2.
TNF-alpha-mediated up-regulation of PDE2 may destabilize endothelial barrier function in sepsis
Title: Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability.
Inhibition of PDE2 resulted in higher levels of intracellular cAMP than inhibition of PDE3A suggesting this PDE may be the more important regulator of cAMP in human platelets.
Title: Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases.
roles of GAF domains in mouse phosphodiesterase 2A [PDE2a]
Title: The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding.

Submit: New GeneRIF Correction

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat decreases the intracellular levels of cAMP and CREB ser-133 phosphorylation through a signal transduction pathway involving sequential activation of phosphatidylinositol 3-kinase, AKT, and cyclic nucleoside phosphodiesterases	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
O00408	O00408	PDE2A		HPRD	PubMed
BioGRID:111164	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
3',5'-cyclic-nucleotide phosphodiesterase activity	IEA Inferred from Electronic Annotation more info
TPR domain binding	IPI Inferred from Physical Interaction more info	PubMed
cAMP binding	IMP Inferred from Mutant Phenotype more info	PubMed
cGMP binding	IDA Inferred from Direct Assay more info	PubMed
cGMP binding	IMP Inferred from Mutant Phenotype more info	PubMed
cGMP-stimulated cyclic-nucleotide phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
calcium channel activity	TAS Traceable Author Statement more info	PubMed
cyclic-nucleotide phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
drug binding	IDA Inferred from Direct Assay more info	PubMed
drug binding	IPI Inferred from Physical Interaction more info	PubMed
hydrolase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
phosphoric diester hydrolase activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
blood coagulation	TAS Traceable Author Statement more info
cAMP catabolic process	IDA Inferred from Direct Assay more info	PubMed
cAMP catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
cAMP-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
cGMP catabolic process	IDA Inferred from Direct Assay more info	PubMed
cGMP-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
calcium ion transmembrane transport	TAS Traceable Author Statement more info	PubMed
cellular response to cGMP	IDA Inferred from Direct Assay more info	PubMed
cellular response to drug	IEP Inferred from Expression Pattern more info	PubMed
cellular response to drug	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to granulocyte macrophage colony-stimulating factor stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to macrophage colony-stimulating factor stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to mechanical stimulus	ISS Inferred from Sequence or Structural Similarity more info
cellular response to transforming growth factor beta stimulus	IEP Inferred from Expression Pattern more info	PubMed
establishment of endothelial barrier	ISS Inferred from Sequence or Structural Similarity more info
metabolic process	IDA Inferred from Direct Assay more info	PubMed
monocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
negative regulation of cAMP biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein import into nucleus, translocation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
negative regulation of vascular permeability	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of vascular permeability	IMP Inferred from Mutant Phenotype more info	PubMed
protein targeting to mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	ISS Inferred from Sequence or Structural Similarity more info
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
membrane raft	IEA Inferred from Electronic Annotation more info
mitochondrial matrix	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
presynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: cGMP-dependent 3',5'-cyclic phosphodiesterase

Names: cGMP-dependent 3',5'-cyclic phosphodiesterase; cGMP-stimulated phosphodiesterase 1; cGMP-stimulated phosphodiesterase 4; cyclic GMP-stimulated phosphodiesterase

NP_001137311.1

EC 3.1.4.17

NP_001139681.1

EC 3.1.4.17

NP_002590.1

EC 3.1.4.17

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001143839.3 → NP_001137311.1 cGMP-dependent 3',5'-cyclic phosphodiesterase isoform 2 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AI498038, AP005019, BC040974, DA227593, U67733

Consensus CDS

CCDS44670.1

UniProtKB/TrEMBL

F6W5Z0

UniProtKB/Swiss-Prot

O00408

UniProtKB/TrEMBL

Q8IW54

Related

ENSP00000442256, OTTHUMP00000237359, ENST00000544570, OTTHUMT00000397109

Conserved Domains (4) summary

cd00077
Location:648 – 824
Blast Score: 135

HDc; Metal dependent phosphohydrolases with conserved 'HD' motif

pfam00233
Location:648 – 885
Blast Score: 822

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam13185
Location:402 – 542
Blast Score: 139

GAF_2; GAF domain

cl15785
Location:402 – 551
Blast Score: 285

GAF; GAF domain
NM_001146209.2 → NP_001139681.1 cGMP-dependent 3',5'-cyclic phosphodiesterase isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (3) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AI498038, AP005019, AY495087, BC040974, U67733

Consensus CDS

CCDS53678.1

UniProtKB/Swiss-Prot

O00408

UniProtKB/TrEMBL

Q8IW54

Related

ENSP00000446399, OTTHUMP00000237361, ENST00000540345, OTTHUMT00000397111

Conserved Domains (4) summary

cd00077
Location:646 – 822
Blast Score: 134

HDc; Metal dependent phosphohydrolases with conserved 'HD' motif

pfam00233
Location:646 – 883
Blast Score: 823

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam13185
Location:400 – 540
Blast Score: 140

GAF_2; GAF domain

cl15785
Location:400 – 549
Blast Score: 285

GAF; GAF domain
NM_001243784.1 → NP_001230713.1 cGMP-dependent 3',5'-cyclic phosphodiesterase isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (4) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AI498038, AP005019, BC040974, DA219662, DA329075, U67733

UniProtKB/Swiss-Prot

O00408

UniProtKB/TrEMBL

Q8IW54

Conserved Domains (4) summary

cd00077
Location:634 – 810
Blast Score: 135

HDc; Metal dependent phosphohydrolases with conserved 'HD' motif

pfam00233
Location:634 – 871
Blast Score: 826

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam13185
Location:388 – 528
Blast Score: 139

GAF_2; GAF domain

cl15785
Location:388 – 537
Blast Score: 286

GAF; GAF domain
NM_002599.4 → NP_002590.1 cGMP-dependent 3',5'-cyclic phosphodiesterase isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AI498038, AP005019, BC040974, DA243617, U67733

Consensus CDS

CCDS8216.1

UniProtKB/Swiss-Prot

O00408

UniProtKB/TrEMBL

Q8IW54

Related

ENSP00000334910, OTTHUMP00000128215, ENST00000334456, OTTHUMT00000219839

Conserved Domains (4) summary

cd00077
Location:655 – 831
Blast Score: 136

HDc; Metal dependent phosphohydrolases with conserved 'HD' motif

pfam00233
Location:655 – 892
Blast Score: 825

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam13185
Location:409 – 549
Blast Score: 140

GAF_2; GAF domain

cl15785
Location:409 – 558
Blast Score: 285

GAF; GAF domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

72287185..72385494, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

68580048..68680748, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AP003065.2 (8384..70405)	None
genomic	AP005019.1 (62295..98500)	None
genomic	CH471076.1	EAW74861.1
		EAW74862.1
mRNA	AI498038.1	None
mRNA	AK092278.1	BAG52517.1
mRNA	AK095024.1	BAG52972.1
mRNA	AK131525.1	BAD18664.1
mRNA	AK295676.1	BAG58533.1
mRNA	AK312434.1	BAG35343.1
mRNA	AY495087.1	AAS75513.1
mRNA	AY495088.1	AAS75514.1
mRNA	BC040974.1	AAH40974.1
mRNA	BI760519.1	None
mRNA	DA219662.1	None
mRNA	DA227593.1	None
mRNA	DA243617.1	None
mRNA	DA325165.1	None
mRNA	DA329075.1	None
mRNA	DA332549.1	None
mRNA	DA504595.1	None
mRNA	DA801834.1	None
mRNA	DB068707.1	None
mRNA	U67733.1	AAC51320.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O00408.1	GenPept	UniProtKB/Swiss-Prot:O00408
Q5J792	GenPept	UniProtKB/TrEMBL:Q5J792
Q6ZMR1	GenPept	UniProtKB/TrEMBL:Q6ZMR1
Q8IW54	GenPept	UniProtKB/TrEMBL:Q8IW54