Phosphodiesterase 4B, cAMP-specific |
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PDB rendering based on 1f0j. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB
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List of PDB id codes |
1F0J, 1RO6, 1RO9, 1ROR, 1TB5, 1XLX, 1XLZ, 1XM4, 1XM6, 1XMU, 1XMY, 1XN0, 1XOS, 1XOT, 1Y2H, 1Y2J, 2CHM, 2QYL, 3D3P, 3FRG, 3G45, 3GWT, 3HC8, 3HDZ, 3HMV, 3KKT, 3LY2, 3O0J, 3O56, 3O57, 3W5E, 3WD9, 4KP6
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Identifiers |
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Symbols | PDE4B; DPDE4; PDE4B5; PDEIVB |
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External IDs | OMIM: 600127 MGI: 99557 HomoloGene: 1953 ChEMBL: 275 GeneCards: PDE4B Gene |
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EC number | 3.1.4.17 |
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RNA expression pattern |
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More reference expression data |
Orthologs |
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Species | Human | Mouse | |
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Entrez | 5142 | 18578 | |
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Ensembl | ENSG00000184588 | ENSMUSG00000028525 | |
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UniProt | Q07343 | B1AWC8 | |
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RefSeq (mRNA) | NM_001037339 | NM_001177980 | |
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RefSeq (protein) | NP_001032416 | NP_001171451 | |
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Location (UCSC) | Chr 1: 66.26 – 66.84 Mb | Chr 4: 102.09 – 102.61 Mb | |
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PubMed search | | | |
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cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene.[1]
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[1]
Clinical relevance
Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder.[1] PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram.[2] PDE4B is involved in dopamine-associated and stress-related behaviours.[3]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)".
- ↑ Siuciak, JA; Chapin, DS; McCarthy, SA; Martin, AN (June 2007). "Antipsychotic profile of rolipram: efficacy in rats and reduced sensitivity in mice deficient in the phosphodiesterase-4B (PDE4B) enzyme". Psychopharmacology 192 (3): 415–424. doi:10.1007/s00213-007-0727-x. PMID 17333137.
- ↑ Francis, SH; Conti, M; Houslay, MD, ed. (2011). Phosphodiesterases as Drug Targets (PDF). Handbook of Experimental Pharmacology 204. Springer Berlin Heidelberg. doi:10.1007/978-3-642-17969-3. ISBN 978-3-642-17968-6.
Further reading
- Szpirer C, Szpirer J, Rivière M, et al. (1995). "Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4". Cytogenet. Cell Genet. 69 (1–2): 11–4. doi:10.1159/000133927. PMID 7835077.
- Bolger GB, Rodgers L, Riggs M (1994). "Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases". Gene 149 (2): 237–44. doi:10.1016/0378-1119(94)90155-4. PMID 7958996.
- Milatovich A, Bolger G, Michaeli T, Francke U (1994). "Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse". Somat. Cell Mol. Genet. 20 (2): 75–86. doi:10.1007/BF02290677. PMID 8009369.
- McLaughlin MM, Cieslinski LB, Burman M, et al. (1993). "A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA". J. Biol. Chem. 268 (9): 6470–6. PMID 8384210.
- Obernolte R, Bhakta S, Alvarez R, et al. (1993). "The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) reveals a multigene family". Gene 129 (2): 239–47. doi:10.1016/0378-1119(93)90274-7. PMID 8392015.
- Bolger G, Michaeli T, Martins T, et al. (1993). "A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs". Mol. Cell. Biol. 13 (10): 6558–71. PMC 364715. PMID 8413254.
- Huston E, Lumb S, Russell A, et al. (1998). "Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3". Biochem. J. 328 ( Pt 2) (Pt 2): 549–58. PMC 1218954. PMID 9371714.
- Ma D, Wu P, Egan RW, et al. (1999). "Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes". Mol. Pharmacol. 55 (1): 50–7. PMID 9882697.
- Secchiero P, Zella D, Curreli S, et al. (2001). "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14620–5. doi:10.1073/pnas.011512398. PMC 18968. PMID 11114167.
- Zauli G, Milani D, Mirandola P, et al. (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway". FASEB J. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID 11156964.
- Moon E, Lee R, Near R, et al. (2002). "Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia". Clin. Cancer Res. 8 (2): 589–95. PMID 11839681.
- Shepherd M, McSorley T, Olsen AE, et al. (2003). "Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform". Biochem. J. 370 (Pt 2): 429–38. doi:10.1042/BJ20021082. PMC 1223190. PMID 12441002.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Arp J, Kirchhof MG, Baroja ML, et al. (2003). "Regulation of T-Cell Activation by Phosphodiesterase 4B2 Requires Its Dynamic Redistribution during Immunological Synapse Formation". Mol. Cell. Biol. 23 (22): 8042–57. doi:10.1128/MCB.23.22.8042-8057.2003. PMC 262363. PMID 14585965.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
- Smith PG, Wang F, Wilkinson KN, et al. (2005). "The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma". Blood 105 (1): 308–16. doi:10.1182/blood-2004-01-0240. PMID 15331441.
- Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
- Millar JK, Pickard BS, Mackie S, et al. (2005). "DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling". Science 310 (5751): 1187–91. doi:10.1126/science.1112915. PMID 16293762.
- Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
PDB gallery |
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| 1f0j: CATALYTIC DOMAIN OF HUMAN PHOSPHODIESTERASE 4B2B |
| 1ro6: Crystal structure of PDE4B2B complexed with Rolipram (R & S) |
| 1ro9: CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP |
| 1ror: CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH AMP |
| 1tb5: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With AMP |
| 1xlx: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Cilomilast |
| 1xlz: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Filaminast |
| 1xm4: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Piclamilast |
| 1xm6: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R)-Mesopram |
| 1xmu: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Roflumilast |
| 1xmy: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R)-Rolipram |
| 1xn0: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R,S)-Rolipram |
| 1xos: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Sildenafil |
| 1xot: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Vardenafil |
| 1y2h: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With 1-(2-chloro-phenyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester |
| 1y2j: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With 3,5-dimethyl-1-(3-nitro-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester |
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