PDE4A phosphodiesterase 4A [Homo sapiens (human)] - Gene

Summary

Official Symbol: PDE4Aprovided by HGNC
Official Full Name: phosphodiesterase 4Aprovided by HGNC
Primary source: HGNC:HGNC:8780
See related: Ensembl:ENSG00000065989 MIM:600126; AllianceGenome:HGNC:8780
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PDE4; DPDE2; PDE46
Summary: The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]
Expression: Ubiquitous expression in testis (RPKM 5.3), brain (RPKM 5.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (10416773..10469631)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (10543231..10596068)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (10527449..10580307)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.
Title: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.
Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
Title: Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.
Title: Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.
Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behcet's Disease.
Title: Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behçet's Disease.
Phosphodiesterase (PDE) 4 inhibition boosts Schwann cell myelination in a 3D regeneration model.
Title: Phosphodiesterase (PDE) 4 inhibition boosts Schwann cell myelination in a 3D regeneration model.
Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.
Title: Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.
Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation.
Title: Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation.
The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease.
Title: The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease.
Overexpression of PDE4A Acts as Checkpoint Inhibitor Against cAMP-Mediated Immunosuppression in vitro.
Title: Overexpression of PDE4A Acts as Checkpoint Inhibitor Against cAMP-Mediated Immunosuppression in vitro.
these results suggest that FCPR16 (PDE4 Inhibitor)is effective in protecting SH-SY5Y cells and neurons against oxidative stress via AMPK-dependent autophagy. Our findings indicate the potential application of FCPR16 in Parkinson's disease (PD) treatment.
Title: Inhibition of PDE4 by FCPR16 induces AMPK-dependent autophagy and confers neuroprotection in SH-SY5Y cells and neurons exposed to MPP(+)-induced oxidative insult.

Submit: New GeneRIF Correction See all GeneRIFs (60)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity	PubMed
	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
	tat	HIV-1 Tat protein, in combination with anti-CD3/CD28 mAbs, promotes IL-2 production and proliferation of primary CD4+ T lymphocytes by recruiting cyclic nucleoside phosphodiesterase 4, resulting in increased susceptibility to HIV-1 infection	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G06567 (e-PCR)
- UniSTS:34058

PDE4A (e-PCR)
- UniSTS:504116

RH98678 (e-PCR)
- UniSTS:86614

PDE4A (e-PCR)
- UniSTS:254044

PDE4Asts1 (e-PCR)
- UniSTS:254044

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3',5'-cyclic-AMP phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3',5'-cyclic-AMP phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables 3',5'-cyclic-AMP phosphodiesterase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables 3',5'-cyclic-AMP phosphodiesterase activity	TAS Traceable Author Statement more info
enables 3',5'-cyclic-GMP phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cAMP binding	IGI Inferred from Genetic Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
involved_in cAMP catabolic process	IEA Inferred from Electronic Annotation more info
involved_in cAMP-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein kinase A signaling	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of smell	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in perinuclear region of cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in ruffle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: 3',5'-cyclic-AMP phosphodiesterase 4A; cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Names: cAMP-specific phosphodiesterase 4A; phosphodiesterase 4A, cAMP-specific (dunce; phosphodiesterase E2 dunce homolog, Drosophila; phosphodiesterase isozyme 4

NP_001104777.1

EC 3.1.4.53

NP_001104778.1

EC 3.1.4.53

NP_001104779.1

EC 3.1.4.53

NP_001230050.1

EC 3.1.4.53

NP_006193.1

EC 3.1.4.53

XP_011526357.1

EC 3.1.4.53

XP_016882354.1

EC 3.1.4.53

XP_047294866.1

EC 3.1.4.53

XP_047294867.1

EC 3.1.4.53

XP_047294868.1

EC 3.1.4.53

XP_047294869.1

EC 3.1.4.53

XP_047294870.1

EC 3.1.4.53

XP_047294871.1

EC 3.1.4.53

XP_054177156.1

EC 3.1.4.53

XP_054177157.1

EC 3.1.4.53

XP_054177158.1

EC 3.1.4.53

XP_054177159.1

EC 3.1.4.53

XP_054177160.1

EC 3.1.4.53

XP_054177161.1

EC 3.1.4.53

XP_054177162.1

EC 3.1.4.53

XP_054177163.1

EC 3.1.4.53

NCBI Reference Sequences (RefSeq)

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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.

Genomic

NG_029594.1 RefSeqGene

Range

8766..57858

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001111307.2 → NP_001104777.1 3',5'-cyclic-AMP phosphodiesterase 4A isoform 1

See identical proteins and their annotated locations for NP_001104777.1

Status: REVIEWED

Description

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

Source sequence(s)

AC011461, AC011548, BC038234, BE266386, BQ009232, L20965

Consensus CDS

CCDS45961.1

UniProtKB/Swiss-Prot

O75522, O76092, P27815, Q16255, Q16691, Q5DM53, Q6PMT2, Q8IVA7, Q8WUQ3, Q9H3H2

Related

ENSP00000370078.3, ENST00000380702.7

Conserved Domains (1) summary

pfam00233
Location:432 → 673

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_001111308.1 → NP_001104778.1 3',5'-cyclic-AMP phosphodiesterase 4A isoform 2

See identical proteins and their annotated locations for NP_001104778.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as PDE4A11) contains an alternative 5' terminal exon compared to variant 1. It encodes a shorter isoform (2) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC011461, AW138155, AY593872, AY618547, BC038234, BE266386, BQ009232, L20965

Consensus CDS

CCDS45962.1

UniProtKB/Swiss-Prot

P27815

Related

ENSP00000293683.4, ENST00000293683.9

Conserved Domains (1) summary

pfam00233
Location:406 → 647

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_001111309.1 → NP_001104779.1 3',5'-cyclic-AMP phosphodiesterase 4A isoform 3

See identical proteins and their annotated locations for NP_001104779.1

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as HSPDE4A10) contains an alternative 5' terminal exon compared to variant 1. It encodes a shorter isoform (3) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC011461, AF073745, AW138155, BC038234, BE266386, BQ009232, L20965

Consensus CDS

CCDS45963.1

UniProtKB/Swiss-Prot

P27815

Related

ENSP00000394754.1, ENST00000440014.6

Conserved Domains (1) summary

pfam00233
Location:371 → 612

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_001243121.2 → NP_001230050.1 3',5'-cyclic-AMP phosphodiesterase 4A isoform 5

See identical proteins and their annotated locations for NP_001230050.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains additional exons at the 5' end compared to variant 1. It encodes a shorter isoform (5, also known as PDE4A8) with a distinct N-terminus compared to isoform 1. This isoform is expressed predominantly in skeletal muscle and brain, a pattern that differs from that of other isoforms, and thus may have a specific function in regulating cAMP levels in human skeletal muscle and brain (PMID:18095939).

Source sequence(s)

AC011461, AC011548, AW138155, AY593872, S75213

Consensus CDS

CCDS58649.1

UniProtKB/Swiss-Prot

P27815

Related

ENSP00000468507.1, ENST00000592685.5

Conserved Domains (1) summary

pfam00233
Location:410 → 651

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_006202.3 → NP_006193.1 3',5'-cyclic-AMP phosphodiesterase 4A isoform 4

See identical proteins and their annotated locations for NP_006193.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternative 5' terminal exon and is missing several 5' coding exons compared to variant 1. It encodes a shorter isoform (4) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC011461, AC011529, BC038234, BE266386, BQ009232, L20965

Consensus CDS

CCDS12238.1

UniProtKB/Swiss-Prot

P27815

Related

ENSP00000341007.2, ENST00000344979.7

Conserved Domains (1) summary

pfam00233
Location:193 → 434

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

10416773..10469631

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047438910.1 → XP_047294866.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X2
XM_011528055.4 → XP_011526357.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X5

Conserved Domains (1) summary

pfam00233
Location:432 → 643

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
XM_017026865.3 → XP_016882354.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X1
XM_047438913.1 → XP_047294869.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X6
XM_047438911.1 → XP_047294867.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X3
XM_047438914.1 → XP_047294870.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X7
XM_047438912.1 → XP_047294868.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X4
XM_047438915.1 → XP_047294871.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X8

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

10543231..10596068

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054321182.1 → XP_054177157.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X2
XM_054321185.1 → XP_054177160.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X5
XM_054321181.1 → XP_054177156.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X1
XM_054321186.1 → XP_054177161.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X6
XM_054321183.1 → XP_054177158.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X3
XM_054321187.1 → XP_054177162.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X7
XM_054321184.1 → XP_054177159.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X4
XM_054321188.1 → XP_054177163.1 cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X8