Reviewed,
UniProtKB/Swiss-Prot P14646 (PDE4B_RAT)
Last modified
January 19, 2010.
Version 81.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (2) |
 Third-party data |
 Customize display | text xml rdf/xml gff fasta |
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: cAMP-specific 3',5'-cyclic phosphodiesterase 4B EC=3.1.4.17 Alternative name(s): DPDE4 | ||
| Gene names |
| ||
| Organism | Rattus norvegicus (Rat) | ||
| 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 |
| Induction | By FSH in Sertoli cells. Ref.1 |
| 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. KM=5.4 µM for cAMP (isoform 4) |
Ontologies
| Keywords | |
|---|---|
| Coding sequence diversity | Alternative splicing |
| Ligand | Metal-binding cAMP |
| Molecular function | Hydrolase |
| PTM | Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | cAMP catabolic process Inferred from direct assay. Source: RGD signal transductionInferred from electronic annotation. Source: InterPro |
| Cellular component | cytosol Ref.5 Inferred from direct assay. Source: RGD insoluble fractionInferred from direct assay. Source: RGD nucleusInferred from direct assay. Source: RGD perinuclear region of cytoplasmInferred from direct assay. Source: RGD soluble fractionInferred from direct assay. Source: RGD |
| Molecular function | 3',5'-cyclic-AMP phosphodiesterase activity Ref.5 Inferred from direct assay. Source: RGD |
| Complete GO annotation... | |
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
| ||||||||||||||||||||||||||||||||||||||||||
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: 1655746] [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: 7958996] [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: 8276818] [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: 9371714] [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: 12441002] [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: 15489334] [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: 2542941] [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: 2546153] [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: 16641100] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-184; SER-272 AND TYR-274, MASS SPECTROMETRY. Tissue: Kidney. |
| + | 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. |
| UniGene | Rn.37733 |
3D structure databases | |
| SMR | P14646. Positions 324-657, 335-685. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P14646. |
PTM databases | |
| PhosphoSite | P14646. |
Genome annotation databases | |
| Ensembl | ENSRNOT00000007738; ENSRNOP00000007738; ENSRNOG00000005905; Rattus norvegicus. [Genome view] |
| GeneID | 24626. |
| KEGG | rno:24626. |
| UCSC | NM_017031. rat. |
Organism-specific databases | |
| CTD | 24626. |
| RGD | 3280. Pde4b. |
Phylogenomic databases | |
| eggNOG | roNOG12318. |
| HOVERGEN | P14646. |
Enzyme and pathway databases | |
| BRENDA | 3.1.4.17. 248. |
Gene expression databases | |
| ArrayExpress | P14646. |
| Genevestigator | P14646. |
| GermOnline | ENSRNOG00000005905. Rattus norvegicus. |
Family and domain databases | |
| InterPro | IPR003607. Metal-dep_PHydrolase_HD_dom. IPR002073. PDEase. [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 Resources | |
| NextBio | 603894. |
Entry information
| Entry name | PDE4B_RAT | ||||||||
| Accession | Primary (citable) accession number: P14646 Secondary accession number(s): Q5RKL0, Q8VD81, Q8VD82 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |
