P14646 (PDE4B_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 104.
History...
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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: cAMP-specific 3',5'-cyclic phosphodiesterase 4B EC=3.1.4.17 Alternative name(s): DPDE4 | ||
| Gene names |
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| Organism | Rattus norvegicus (Rat) [Reference proteome] | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 736 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes By similarity. |
| Catalytic activity | Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate. |
| Cofactor | Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions By similarity. |
| Enzyme regulation | Expression is under the control of follicle-stimulating hormone and cAMP. Inhibited by rolipram. |
| Pathway | Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. |
| Tissue specificity | Widely expressed. Isoform 3 expressed in brain, heart, lung and liver. Isoform 4 expressed in liver and brain. Ref.5 Ref.10 |
| Induction | In Sertoli cells, induced by FSH. In the pineal gland, exhibits night/day variations with a 7-fold increased expression at night. Up-regulation is due to a large degree to the release of norepinephrine from nerve terminals in the pineal gland and cAMP signaling pathway. Ref.1 Ref.10 |
| Sequence similarities | Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily. |
| Biophysicochemical properties | Kinetic parameters: Vmax values for isoforms 2, 3 and 4 relative to isoform 1 are 3.8, 1.6 and 2.1. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P14646-3) Also known as: PDE4B1; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P14646-2) Also known as: PDE4B2; The sequence of this isoform differs from the canonical sequence as follows: 1-172: Missing. 173-211: LASLRIVRNN...QAPVTRVSLQ → MKEQGGTVSG...PNYLSVCLFA | ||||||
| Isoform 3 (identifier: P14646-1) Also known as: PDE4B3; The sequence of this isoform differs from the canonical sequence as follows: 1-93: MKKSRSVMAV...SIAITTVSQE → MTAKNSSKEL...QRRRFTVAHT | ||||||
| Isoform 4 (identifier: P14646-4) Also known as: PDE4B4; The sequence of this isoform differs from the canonical sequence as follows: 1-93: MKKSRSVMAV...SIAITTVSQE → MLHVNDLPPPRRHSWI | ||||||
| Note: Activated by phosphorylation at Ser-56. Mutagenesis of Ser-56 abolishes activation. | ||||||
| Isoform 5 (identifier: P14646-5) The sequence of this isoform differs from the canonical sequence as follows: 1-93: MKKSRSVMAV...SIAITTVSQE → MTAKNSSKEL...QRRRFTVAHT 710-736: VIDPENRDSLEETDIDIATEDKSLIDT → KPCHAANGLALPVGGGNAASTQPRCGHV | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 736 | 736 | cAMP-specific 3',5'-cyclic phosphodiesterase 4B | PRO_0000198810 | |||||
Regions | |||||||||
| Nucleotide binding | 406 – 410 | 5 | cAMP By similarity | ||||||
Sites | |||||||||
| Active site | 406 | 1 | Proton donor By similarity | ||||||
| Metal binding | 410 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 446 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 447 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 447 | 1 | Divalent metal cation 2 By similarity | ||||||
| Metal binding | 564 | 1 | Divalent metal cation 1 By similarity | ||||||
| Binding site | 447 | 1 | cAMP By similarity | ||||||
| Binding site | 564 | 1 | cAMP By similarity | ||||||
| Binding site | 615 | 1 | cAMP By similarity | ||||||
| Site | 567 | 1 | Binds AMP, but not cAMP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 184 | 1 | Phosphothreonine Ref.9 | ||||||
| Modified residue | 272 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 274 | 1 | Phosphotyrosine Ref.9 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 172 | 172 | Missing in isoform 2. | VSP_026678 | |||||
| Alternative sequence | 1 – 93 | 93 | MKKSR…TVSQE → MTAKNSSKELPASESEVCIK TFKEQMRLELELPKLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform 3 and isoform 5. | VSP_026679 | |||||
| Alternative sequence | 1 – 93 | 93 | MKKSR…TVSQE → MLHVNDLPPPRRHSWI in isoform 4. | VSP_026680 | |||||
| Alternative sequence | 173 – 211 | 39 | LASLR…RVSLQ → MKEQGGTVSGAGSSRGGGDS AMASLQPLQPNYLSVCLFA in isoform 2. | VSP_004573 | |||||
| Alternative sequence | 710 – 736 | 27 | VIDPE…SLIDT → KPCHAANGLALPVGGGNAAS TQPRCGHV in isoform 5. | VSP_026681 | |||||
Experimental info | |||||||||
| Sequence conflict | 178 | 1 | I → S in AAL31763. Ref.5 | ||||||
| Sequence conflict | 178 | 1 | I → S in AAL31764. Ref.5 | ||||||
| Sequence conflict | 178 | 1 | I → S in AAH85704. Ref.6 | ||||||
| Sequence conflict | 531 | 1 | T → S in AAA18926. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Properties and hormonal regulation of two structurally related cAMP phosphodiesterases from the rat Sertoli cell." Swinnen J.V., Tsikalas K.E., Conti M. J. Biol. Chem. 266:18370-18377(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION. Tissue: Sertoli cell. |
| [2] | "Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases." Bolger G.B., Rodgers L., Riggs M. Gene 149:237-244(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [3] | "Structure of two rat genes coding for closely related rolipram-sensitive cAMP phosphodiesterases. Multiple mRNA variants originate from alternative splicing and multiple start sites." Monaco L., Vicini E., Conti M. J. Biol. Chem. 269:347-357(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: Wistar. |
| [4] | "Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3." Huston E., Lumb S., Russell A., Catterall C., Ross A.H., Steele M.R., Bolger G.B., Perry M.J., Owens R.J., Houslay M.D. Biochem. J. 328:549-558(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Olfactory bulb. |
| [5] | "Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform." Shepherd M., McSorley T., Olsen A.E., Johnston L.A., Thomson N.C., Baillie G.S., Houslay M.D., Bolger G.B. Biochem. J. 370:429-438(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Brain cortex. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Heart. |
| [7] | "Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase." Colicelli J., Birchmeier C., Michaeli T., O'Neill K., Riggs M., Wigler M. Proc. Natl. Acad. Sci. U.S.A. 86:3599-3603(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 175-736. Tissue: Brain. |
| [8] | "Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes." Swinnen J.V., Joseph D.R., Conti M. Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 304-663. Tissue: Testis. |
| [9] | "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-184; SER-272 AND TYR-274, MASS SPECTROMETRY. Tissue: Renal collecting duct. |
| [10] | "Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling." Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q., Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F., Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C. J. Biol. Chem. 284:7606-7622(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | L27058 mRNA. Translation: AAA74478.1. U01291  U01290 Unassigned DNA. Translation: AAA18926.1.U95748 mRNA. Translation: AAB96560.1. AF202732 mRNA. Translation: AAL31763.1. AF202733 mRNA. Translation: AAL31764.1. BC085704 mRNA. Translation: AAH85704.1. J04563 mRNA. Translation: AAA66039.1. M25350 mRNA. Translation: AAA41846.1. M28413 mRNA. Translation: AAA41824.1. |
| IPI | IPI00202428. IPI00231010. IPI00557492. IPI00854038. IPI00854041. |
| PIR | A40949. I59143. |
| RefSeq | NP_058727.2. NM_017031.2. |
| UniGene | Rn.37733. |
3D structure databases | |
| ProteinModelPortal | P14646. |
| SMR | P14646. Positions 324-685. |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | P14646. |
Proteomic databases | |
| PaxDb | P14646. |
| PRIDE | P14646. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSRNOT00000007738; ENSRNOP00000007738; ENSRNOG00000005905. |
| GeneID | 24626. |
| KEGG | rno:24626. |
| UCSC | RGD:3280. rat. |
Organism-specific databases | |
| CTD | 5142. |
| RGD | 3280. Pde4b. |
Phylogenomic databases | |
| eggNOG | NOG122287. |
| GeneTree | ENSGT00690000101692. |
| HOGENOM | HOG000236297. |
| HOVERGEN | HBG108239. |
| InParanoid | P14646. |
| KO | K01120. |
| OrthoDB | EOG4ZGPBT. |
Enzyme and pathway databases | |
| UniPathway | UPA00762; UER00747. |
Gene expression databases | |
| ArrayExpress | P14646. |
| Genevestigator | P14646. |
| GermOnline | ENSRNOG00000005905. Rattus norvegicus. |
Family and domain databases | |
| Gene3D | 1.10.1300.10. 1 hit. |
| InterPro | IPR003607. HD/PDEase_dom. IPR023088. PDEase. IPR002073. PDEase_catalytic_dom. IPR023174. PDEase_CS. [Graphical view] |
| Pfam | PF00233. PDEase_I. 1 hit. [Graphical view] |
| PRINTS | PR00387. PDIESTERASE1. |
| SMART | SM00471. HDc. 1 hit. [Graphical view] |
| PROSITE | PS00126. PDEASE_I. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | P14646. |
| ChEMBL | CHEMBL3382. |
| NextBio | 603894. |
Entry information
| Entry name | PDE4B_RAT | ||||||||
| Accession | Primary (citable) accession number: P14646 Secondary accession number(s): Q5RKL0, Q8VD81, Q8VD82 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |