Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Pde4d. (This text reflects annotations as of Thursday, January 16, 2014.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Pde4d
  • participates in the following biological processes:
    • cAMP catabolic process ^[5]
  • performs the following molecular functions:
    • 3',5'-cyclic-nucleotide phosphodiesterase activity ^[5]
  • is located in the following cellular components:
    • calcium channel complex ^[4]
    • voltage-gated calcium channel complex ^[5]
• The gene product of Pde4d has been shown to bind to the gene products of Adrb1. ^[7] Researchers have inferred, based on physical interactions, that the gene product of Pde4d
  • performs the following molecular functions:
    • ATPase binding ^[2]
    • ion channel binding ^{[4, 5]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Pde4d
  • participates in the following biological processes:
    • aging ^[3]
    • cAMP catabolic process ^[6]
    • cellular response to epinephrine stimulus ^[4]
    • cellular response to lipopolysaccharide ^[1]
    • leukocyte migration ^[1]
    • multicellular organism growth ^[3]
    • negative regulation of heart contraction ^[2]
    • negative regulation of peptidyl-serine phosphorylation ^[4]
    • negative regulation of relaxation of cardiac muscle ^[5]
    • neutrophil chemotaxis ^[1]
    • regulation of cardiac muscle cell contraction ^{[2, 5]}
    • regulation of heart rate ^[4]
    • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum ^[4]
    • regulation of ryanodine-sensitive calcium-release channel activity ^[4]
    • smooth muscle contraction ^[6]
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Pde4d
  • participates in the following biological processes:
    • regulation of cell communication by electrical coupling involved in cardiac conduction ^[4]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Pde4d:
  • participates in the following biological processes:
    • adrenergic receptor signaling pathway
    • cAMP catabolic process
    • cellular protein complex assembly
    • cellular response to cAMP
    • cellular response to epinephrine stimulus
    • establishment of endothelial barrier
    • memory
    • positive regulation of interferon-gamma production
    • positive regulation of interleukin-2 production
    • positive regulation of interleukin-5 production
    • positive regulation of smooth muscle cell migration
    • positive regulation of smooth muscle cell proliferation
    • regulation of cardiac muscle cell contraction
    • regulation of G-protein coupled receptor protein signaling pathway
    • regulation of protein kinase A signaling
    • regulation of receptor activity
    • T cell receptor signaling pathway
  • performs the following molecular functions:
    • 3',5'-cyclic-AMP phosphodiesterase activity
    • ATPase binding
    • beta-2 adrenergic receptor binding
    • cAMP binding
    • cyclic-nucleotide phosphodiesterase activity
    • drug binding
    • enzyme binding
    • ion channel binding
    • protein domain specific binding
    • scaffold protein binding
    • SH3 domain binding
    • ubiquitin protein ligase binding
  • is located in the following cellular components:
    • calcium channel complex
    • centrosome
    • cytosol
    • Golgi apparatus
    • myofibril
    • plasma membrane

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Summary text based on GO annotations supported by structural data

• Pde4d encodes a protein or proteins that contain the following InterPro domains: 3'5'-cyclic nucleotide phosphodiesterase, 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain, 3'5'-cyclic nucleotide phosphodiesterase, conserved site, HD/PDEase domain, indicating that the gene product:
  • participates in the following biological processes:
    • signal transduction
  • performs the following molecular functions:
    • catalytic activity
    • phosphoric diester hydrolase activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Pde4d indicates that it:
  • performs the following molecular functions:
    • hydrolase activity
    • metal ion binding
  • is located in the following cellular components:
    • cytoplasm
    • cytoskeleton
    • membrane

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References

1. Ariga M et al. (2004) Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation. J Immunol, 173:7531-8. (PubMed:15585880)
2. Beca S et al. (2011) Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-type Ca2+ current. Circ Res, 109:1024-30. (PubMed:21903937)
3. Jin SL et al. (1999) Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice. Proc Natl Acad Sci U S A, 96:11998-2003. (PubMed:10518565)
4. Lehnart SE et al. (2005) Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell, 123:25-35. (PubMed:16213210)
5. Leroy J et al. (2011) Phosphodiesterase 4B in the cardiac L-type Ca(2) channel complex regulates Ca(2) current and protects against ventricular arrhythmias in mice. J Clin Invest, 121:2651-61. (PubMed:21670503)
6. Mehats C et al. (2003) PDE4D plays a critical role in the control of airway smooth muscle contraction. FASEB J, 17:1831-41. (PubMed:14519662)
7. Richter W et al. (2008) Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4. EMBO J, 27:384-93. (PubMed:18188154)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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