Reviewed,
UniProtKB/Swiss-Prot P27815 (PDE4A_HUMAN)
Last modified
June 16, 2009.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: cAMP-specific 3',5'-cyclic phosphodiesterase 4A EC=3.1.4.17 Alternative name(s): DPDE2 PDE46 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 886 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Catalytic activity | Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate. |
| Enzyme regulation | Inhibited by rolipram. |
| Pathway | Purine metabolism; cAMP degradation; AMP from cAMP: step 1/1. |
| Subcellular location | Isoform 4: Membrane; Peripheral membrane protein. Note: Isoform 4 has propensity for association with membranes. |
| Post-translational modification | Phosphorylated at Ser-686 and Ser-688 when expressed in S.frugiperda cells. Ref.8 |
| Sequence similarities | Belongs to the cyclic nucleotide phosphodiesterase family. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing |
| Ligand | cAMP |
| Molecular function | Hydrolase |
| PTM | Phosphoprotein |
| Technical term | 3D-structure |
| Gene Ontology (GO) | |
| Biological process | signal transduction Traceable author statement. Source: ProtInc |
| Cellular component | membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.2Traceable author statement. Source: ProtInc soluble fractionTraceable author statement. Source: ProtInc |
| Molecular function | 3',5'-cyclic-AMP phosphodiesterase activity Ref.2 Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist. | ||||||
| Isoform 1 (identifier: P27815-1) Also known as: PDE46; 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: P27815-2) Also known as: TM3; The sequence of this isoform differs from the canonical sequence as follows: 1-107: MEPPTVPSER...GGAGGGSSRR → MARPRGLGRI...LGRQAWAGAG | ||||||
| Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. | ||||||
| Isoform 3 (identifier: P27815-3) Also known as: PDE4A7; PDE4A6; The sequence of this isoform differs from the canonical sequence as follows: 1-209: MEPPTVPSER...NVPVPSNKRS → MCPFPVTTV | ||||||
| Isoform 4 (identifier: P27815-4) Also known as: PDE4A1; RD1; The sequence of this isoform differs from the canonical sequence as follows: 1-261: MEPPTVPSER...RSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ | ||||||
| Note: Isoform 4 has propensity for association with membranes. | ||||||
| Isoform 5 (identifier: P27815-5) Also known as: PDE4A8; 2EL; The sequence of this isoform differs from the canonical sequence as follows: 1-367: MEPPTVPSER...KTDQEELLAQ → MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ 644-657: GFIDYIVHPLWETW → QARGIDGRAQGGFY 658-886: Missing. | ||||||
| Note: Probably represents a non-functional splice isoform. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 886 | 886 | cAMP-specific 3',5'-cyclic phosphodiesterase 4A | PRO_0000198806 | |||||
Regions | |||||||||
| Region | 330 – 723 | 394 | Catalytic | ||||||
Amino acid modifications | |||||||||
| Modified residue | 686 | 1 | Phosphoserine Probable | ||||||
| Modified residue | 688 | 1 | Phosphoserine Probable | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 367 | 367 | MEPPT…ELLAQ → MVLPSDQGFKLLGNVLQGPE PYRLLTSGLRLHQ in isoform 5. | VSP_004559 | |||||
| Alternative sequence | 1 – 261 | 261 | MEPPT…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 4. | VSP_004558 | |||||
| Alternative sequence | 1 – 209 | 209 | MEPPT…SNKRS → MCPFPVTTV in isoform 3. | VSP_004557 | |||||
| Alternative sequence | 1 – 107 | 107 | MEPPT…GSSRR → MARPRGLGRIPELQLVAFPV AVAAEDEAFLPEPLAPRAPR RPRSPPSSPVFFASPSPTFR RRLRLLRSCQDLGRQAWAGA G in isoform 2. | VSP_004556 | |||||
| Alternative sequence | 644 – 657 | 14 | GFIDY…LWETW → QARGIDGRAQGGFY in isoform 5. | VSP_004560 | |||||
| Alternative sequence | 658 – 886 | 229 | Missing in isoform 5. | VSP_004561 | |||||
Experimental info | |||||||||
| Sequence conflict | 736 | 1 | A → E in AAA69697. Ref.3 | ||||||
| Sequence conflict | 736 | 1 | A → E in AAC50458. Ref.5 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs." Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K. Mol. Cell. Biol. 13:6558-6571(1993) [PubMed: 8413254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2." Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D. Biochem. J. 333:693-703(1998) [PubMed: 9677330] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3; 4 AND 5). Tissue: Brain. |
| [3] | "Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase." Livi G.P., Kmetz P., McHale M.M., Cieslinski L.B., Sathe G.M., Taylor D.P., Davis R.L., Torphy T.J., Balcarek J.M. Mol. Cell. Biol. 10:2678-2686(1990) [PubMed: 2160582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-886. Tissue: Monocyte. |
| [4] | McLaughlin M.M. Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [5] | "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19." Horton Y.M., Sullivan M., Houslay M.D. Biochem. J. 308:683-691(1995) [PubMed: 7772058] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5). |
| [6] | "Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)." Sullivan M., Egerton M., Shakur Y., Marquardsen A., Houslay M.D. Cell. Signal. 6:793-812(1994) [PubMed: 7888306] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). |
| [7] | "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 4). Tissue: Brain. |
| [8] | "Purification and characterization of the human pde4a catalytic domain (pde4a(330-723)) expressed in sf9 cells." Lario P.I., Bobechko B., Bateman K., Kelly J., Vrielink A., Huang Z. Arch. Biochem. Biophys. 394:54-60(2001) [PubMed: 11566027] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-686 AND SER-688, MASS SPECTROMETRY. |
| [9] | "An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L20965 mRNA. Translation: AAA03588.1. AF069491 AF069490 Genomic DNA. Translation: AAC35012.1. AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35013.1. AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35014.1. AF069491 AF069490 Genomic DNA. Translation: AAC35015.1. U68532 mRNA. Translation: AAC63832.1. U97584 mRNA. Translation: AAC25679.1. M37744 mRNA. Translation: AAA69697.1. U18087 mRNA. Translation: AAC50458.1. U18088 mRNA. Translation: AAA98540.1. S75213 mRNA. Translation: AAB33798.1. BC019864 mRNA. Translation: AAH19864.1. | |||||||||||||
| IPI | IPI00006232. IPI00020973. IPI00171460. IPI00220048. IPI00220052. | ||||||||||||
| PIR | A54442. S55348. | ||||||||||||
| RefSeq | NP_001104777.1. | ||||||||||||
| UniGene | Hs.89901 | ||||||||||||
3D structure databases | |||||||||||||
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| ModBase | Search... | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P27815. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | P27815. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000065989. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 5141. | ||||||||||||
| KEGG | hsa:5141. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC19P010392. | ||||||||||||
| H-InvDB | HIX0014746. | ||||||||||||
| HGNC | HGNC:8780. PDE4A. | ||||||||||||
| HPA | CAB017632. | ||||||||||||
| MIM | 600126. gene. | ||||||||||||
| PharmGKB | PA33128. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | P27815. | ||||||||||||
| HOVERGEN | P27815. | ||||||||||||
| OMA | P27815. HIPVDTM. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 3.1.4.17. 247. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P27815. | ||||||||||||
| Bgee | P27815. | ||||||||||||
| CleanEx | HS_PDE4A. | ||||||||||||
| GermOnline | ENSG00000065989. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR003607. Met-dep_phosphohydro_HD. 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 | |||||||||||||
| DrugBank | DB01166. Cilostazol. DB00975. Dipyridamole. DB00651. Dyphylline. DB00824. Enprofylline. DB01088. Iloprost. DB00235. Milrinone. DB00806. Pentoxifylline. DB00692. Phentolamine. DB00820. Tadalafil. DB00277. Theophylline. | ||||||||||||
| NextBio | 19824. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | PDE4A_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P27815 Secondary accession number(s): O75522 Q8WUQ3 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 19 Human chromosome 19: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


