cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B

Function

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological process. Regulates angiogenesis by inhibiting the cAMP-dependent guanine nucleotide exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma-mediated signaling. Controls cardiac contractility by reducing cAMP concentration in cardiocytes (By similarity).

Classification

Family (Pfam)

PF00233 PDEase_I

InterPro

HD/PDEase_dom, PDEase_catalytic_dom, PDEase_catalytic_dom_sf, PDEase_CS

Functional cluster

RNA Polymerase II Transcription Factors

Experimental structures · PDB · 4

• 1SO2 X-ray 2.40A
• 1SOJ X-ray 2.90A
• 8SYC X-ray 2.70A
• 9YUD X-ray 2.70A

A predicted model is available from AlphaFold.

Gene Ontology · 21

• GO:0005829 cytosol
• GO:0005783 endoplasmic reticulum
• GO:0005794 Golgi apparatus
• GO:0032045 guanyl-nucleotide exchange factor complex
• GO:0016020 membrane
• GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
• GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
• GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
• GO:0046872 metal ion binding
• GO:0043422 protein kinase B binding
• GO:0001525 angiogenesis
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0008286 insulin receptor signaling pathway
• GO:0106072 negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0016525 negative regulation of angiogenesis
• GO:0141162 negative regulation of cAMP/PKA signal transduction
• GO:0007162 negative regulation of cell adhesion
• GO:0033629 negative regulation of cell adhesion mediated by integrin
• GO:0050995 negative regulation of lipid catabolic process
• GO:0045765 regulation of angiogenesis
• GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Drugs targeting this protein · 11

• OXTRIPHYLLINE inhibitor
• THEOPHYLLINE SODIUM GLYCINATE inhibitor
• ANAGRELIDE HYDROCHLORIDE inhibitor
• THEOPHYLLINE inhibitor
• AMINOPHYLLINE inhibitor
• LEVOSIMENDAN inhibitor
• ENOXIMONE inhibitor
• K-134 inhibitor
• ENSIFENTRINE inhibitor
• PENTOXIFYLLINE inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B 0.97
• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B 0.97
• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A 0.91
• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A 0.89
• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A 0.89
• TBC1 domain family member 14 0.63
• TBC1 domain family member 14 0.62
• TBC1 domain family member 14 0.61
• TBC1 domain family member 12 0.61
• TBC1 domain family member 14 0.61
• Single-minded homolog 1-A 0.59
• Single-minded homolog 2 0.56

Co-cited proteins · studied together in the literature

• cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B 2 shared papers
• Phosphoinositide 3-kinase regulatory subunit 6 1 shared papers
• Rap guanine nucleotide exchange factor 3 1 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 1 shared papers

Literature · 13 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J. Biol. Chem. · 2011
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J. Proteome Res. · 2008
• Importance of cAMP-response element-binding protein in regulation of expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b) gene in differentiating 3T3-L1 preadipocytes. J. Biol. Chem. · 2006
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity. Biochemistry · 2004
• Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors. Bioorg. Med. Chem. Lett. · 2003
• Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A) -- a gene involved in fat metabolism located at 11p15.1. Genomics · 1996
• Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family. Genomics · 1996
• … and 1 more in the literature graph