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PDE4A phosphodiesterase 4A [ Homo sapiens (human) ]

Gene ID: 5141, updated on 7-Dec-2018

Summary

Official Symbol
PDE4Aprovided by HGNC
Official Full Name
phosphodiesterase 4Aprovided by HGNC
Primary source
HGNC:HGNC:8780
See related
Ensembl:ENSG00000065989 MIM:600126
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

Genomic context

See PDE4A in Genome Data Viewer
Location:
19p13.2
Exon count:
22
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 19 NC_000019.10 (10416773..10469631)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (10527449..10580307)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene tyrosine kinase 2 Neighboring gene cell division cycle 37 Neighboring gene microRNA 1181 Neighboring gene kelch like ECH associated protein 1 Neighboring gene sphingosine-1-phosphate receptor 5

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • DARPP-32 events, organism-specific biosystem (from REACTOME)
    DARPP-32 events, organism-specific biosystemDopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified as a major target for dopamine and protein kinase A (PKA) in striatum. Recent advances now indicate that regulation D...
  • G Protein Signaling Pathways, organism-specific biosystem (from WikiPathways)
    G Protein Signaling Pathways, organism-specific biosystemG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. G proteins are so called because they function as "molecular switches". They...
  • G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
  • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
    GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
  • Morphine addiction, organism-specific biosystem (from KEGG)
    Morphine addiction, organism-specific biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
  • Morphine addiction, conserved biosystem (from KEGG)
    Morphine addiction, conserved biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
  • Opioid Signalling, organism-specific biosystem (from REACTOME)
    Opioid Signalling, organism-specific biosystemOpioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as...
  • Purine metabolism, organism-specific biosystem (from KEGG)
    Purine metabolism, organism-specific biosystem
    Purine metabolism
  • Purine metabolism, conserved biosystem (from KEGG)
    Purine metabolism, conserved biosystem
    Purine metabolism
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • cAMP signaling pathway, organism-specific biosystem (from KEGG)
    cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
  • cAMP signaling pathway, conserved biosystem (from KEGG)
    cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
3',5'-cyclic-AMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
3',5'-cyclic-AMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
PubMed 
3',5'-cyclic-AMP phosphodiesterase activity IGI
Inferred from Genetic Interaction
more info
PubMed 
3',5'-cyclic-AMP phosphodiesterase activity TAS
Traceable Author Statement
more info
 
cAMP binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cAMP binding IGI
Inferred from Genetic Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
cAMP catabolic process IEA
Inferred from Electronic Annotation
more info
 
cellular response to drug IEA
Inferred from Electronic Annotation
more info
 
regulation of cAMP-mediated signaling IEA
Inferred from Electronic Annotation
more info
 
regulation of protein kinase A signaling IEA
Inferred from Electronic Annotation
more info
 
sensory perception of smell IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
membrane TAS
Traceable Author Statement
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
perinuclear region of cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
 
ruffle membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Names
phosphodiesterase 4A, cAMP-specific (dunce
phosphodiesterase E2 dunce homolog, Drosophila
phosphodiesterase isozyme 4
NP_001104777.1
NP_001104778.1
NP_001104779.1
NP_001230050.1
NP_006193.1
XP_011526356.1
XP_011526357.1
XP_016882354.1
XP_024307302.1

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.

Genomic

  1. NG_029594.1 RefSeqGene

    Range
    5001..57859
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001111307.2NP_001104777.1  cAMP-specific 3',5'-cyclic 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
    P27815
    Related
    ENSP00000370078.3, ENST00000380702.6
    Conserved Domains (1) summary
    pfam00233
    Location:432673
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  2. NM_001111308.1NP_001104778.1  cAMP-specific 3',5'-cyclic 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:406647
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  3. NM_001111309.1NP_001104779.1  cAMP-specific 3',5'-cyclic 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:371612
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  4. NM_001243121.1NP_001230050.1  cAMP-specific 3',5'-cyclic 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:410651
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  5. NM_006202.2NP_006193.1  cAMP-specific 3',5'-cyclic 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, AW138155, BC038234, BE266386, BQ009232, L20965
    Consensus CDS
    CCDS12238.1
    UniProtKB/Swiss-Prot
    P27815
    Related
    ENSP00000341007.2, ENST00000344979.7
    Conserved Domains (1) summary
    pfam00233
    Location:193434
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p12 Primary Assembly

    Range
    10416773..10469631
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011528054.1XP_011526356.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X2

    See identical proteins and their annotated locations for XP_011526356.1

    UniProtKB/Swiss-Prot
    P27815
    Conserved Domains (1) summary
    pfam00233
    Location:410651
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  2. XM_017026865.2XP_016882354.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X1

  3. XM_011528055.3XP_011526357.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X3

    Conserved Domains (1) summary
    pfam00233
    Location:432643
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  4. XM_024451534.1XP_024307302.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X4

    Conserved Domains (1) summary
    pfam00233
    Location:128365
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
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