PDE4D

PDE4D

PDE4D

PDE4D
Identifiers
AliasesPDE4D, ACRDYS2, DPDE3, HSPDE43, PDE4DN2, STRK1, phosphodiesterase 4D
External IDsOMIM: 600129; MGI: 99555; GeneCards: PDE4D
Available structures
PDBOrtholog search: PDBe RCSB
Enzyme activity
EC #BRENDAExPASyKEGGMetaCyc
3.1.4.53↗↗↗↗
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

5144

238871

Ensembl

ENSG00000113448

ENSMUSG00000021699

UniProt

Q08499

Q01063

RefSeq (mRNA)

NM_011056
NM_177252

RefSeq (protein)
Location (UCSC)Chr 5: 58.97 – 60.52 MbChr 13: 108.59 – 110.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene.

Function

The PDE4D gene is complex and has at least 9 different isoforms that encode functional proteins. These proteins degrade the second messenger cAMP, which is a key signal transduction molecule in multiple cell types, including vascular cells (Dominiczak and McBride, 2003).[supplied by OMIM][5]

Interactions

PDE4D has been shown to interact with myomegalin[6] and GNB2L1.[7][8]

Clinical relevance

Mutations in this gene have been associated to cases of acrodysostosis.[9]

This is the subtype of PDE4 that appears to be involved in the emetic and antidepressant effects of PDE4 inhibitors.[10]

Furthermore, changes in expression of the isoform PDE4D7 have been proposed as prostate cancer biomarker. [11] [12] [13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113448 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021699 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: PDE4D phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)".
  6. ^ Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M (Apr 2001). "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal of Biological Chemistry. 276 (14): 11189–98. doi:10.1074/jbc.M006546200. hdl:11573/1681344. PMID 11134006.
  7. ^ Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB (May 1999). "The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform". The Journal of Biological Chemistry. 274 (21): 14909–17. doi:10.1074/jbc.274.21.14909. PMID 10329691.
  8. ^ Steele MR, McCahill A, Thompson DS, MacKenzie C, Isaacs NW, Houslay MD, Bolger GB (Jul 2001). "Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5". Cellular Signalling. 13 (7): 507–13. doi:10.1016/S0898-6568(01)00167-X. PMID 11516626.
  9. ^ Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V (Apr 2012). "Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis". American Journal of Human Genetics. 90 (4): 740–5. doi:10.1016/j.ajhg.2012.03.003. PMC 3322219. PMID 22464250.
  10. ^ Zhang HT (2009). "Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs". Current Pharmaceutical Design. 15 (14): 1688–98. doi:10.2174/138161209788168092. PMID 19442182.
  11. ^ Böttcher R, Henderson DJ, Dulla K, van Strijp D, Waanders LF, Tevz G, Lehman ML, Merkle D, van Leenders GJ, Baillie GS, Jenster G, Houslay MD, Hoffmann R (Nov 2015). "Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG-positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression". British Journal of Cancer. 113 (10): 1502–11. doi:10.1038/bjc.2015.335. PMC 4815894. PMID 26575822.
  12. ^ Böttcher R, Dulla K, van Strijp D, Dits N, Verhoef EI, Baillie GS, van Leenders GJ, Houslay MD, Jenster G, Hoffmann R (Oct 2016). "Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases". Oncotarget. 7 (43): 70669–70684. doi:10.18632/oncotarget.12204. PMC 5342582. PMID 27683107.
  13. ^ Henderson DJ, Byrne A, Dulla K, Jenster G, Hoffmann R, Baillie GS, Houslay MD (Mar 2014). "The cAMP phosphodiesterase-4D7 (PDE4D7) is downregulated in androgen-independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells". British Journal of Cancer. 110 (5): 1278–87. doi:10.1038/bjc.2014.22. PMC 3950871. PMID 24518597.

Further reading

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