O95263 (PDE8B_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 129.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B Short name=HsPDE8B EC=3.1.4.17 Alternative name(s): Cell proliferation-inducing gene 22 protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 885 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. May be involved in specific signaling in the thyroid gland. |
| Catalytic activity | Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate. Ref.2 |
| 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 | Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and milrinone as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP. Ref.2 |
| Pathway | Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. |
| Tissue specificity | Abundantly expressed in the thyroid. Also very weakly expressed in brain, spinal cord and placenta. In the thyroid isoform 1 predominates, and isoforms 2 and 6 are also highly expressed. In the placenta isoforms 1 and 2 are expressed equally. In the brain isoform 2 predominates. Ref.1 Ref.2 |
| Domain | Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain. |
| Involvement in disease | Striatal degeneration autosomal dominant (ADSD) [MIM:609161]: A movement disorder affecting the striatal part of the basal ganglia and characterized by bradykinesia, dysarthria and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. Primary pigmented nodular adrenocortical disease 3 (PPNAD3) [MIM:614190]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. |
| Sequence similarities | Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily. Contains 1 PAS (PER-ARNT-SIM) domain. |
Ontologies
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O95263-1) Also known as: PDE8B1; 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. | ||||||
| Note: Major isoform. | ||||||
| Isoform 2 (identifier: O95263-2) Also known as: PDE8B2; PDE8B3; The sequence of this isoform differs from the canonical sequence as follows: 293-389: Missing. | ||||||
| Isoform 3 (identifier: O95263-3) Also known as: PDE8B3; The sequence of this isoform differs from the canonical sequence as follows: 456-510: Missing. | ||||||
| Isoform 4 (identifier: O95263-4) Also known as: PDE8B4; The sequence of this isoform differs from the canonical sequence as follows: 114-133: Missing. | ||||||
| Isoform 5 (identifier: O95263-5) The sequence of this isoform differs from the canonical sequence as follows: 1-535: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 6 (identifier: O95263-6) Also known as: PDE8B2; The sequence of this isoform differs from the canonical sequence as follows: 293-339: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 885 | 885 | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B | PRO_0000198840 | |||||
Regions | |||||||||
| Domain | 267 – 338 | 72 | PAS | ||||||
| Region | 590 – 868 | 279 | Catalytic By similarity | ||||||
Sites | |||||||||
| Active site | 615 | 1 | Proton donor By similarity | ||||||
| Metal binding | 619 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 655 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 656 | 1 | Divalent metal cation 1 By similarity | ||||||
| Metal binding | 656 | 1 | Divalent metal cation 2 By similarity | ||||||
| Metal binding | 781 | 1 | Divalent metal cation 1 By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 517 | 1 | Phosphoserine Ref.8 Ref.10 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 535 | 535 | Missing in isoform 5. | VSP_008081 | |||||
| Alternative sequence | 114 – 133 | 20 | Missing in isoform 4. | VSP_008082 | |||||
| Alternative sequence | 293 – 389 | 97 | Missing in isoform 2. | VSP_008084 | |||||
| Alternative sequence | 293 – 339 | 47 | Missing in isoform 6. | VSP_008083 | |||||
| Alternative sequence | 456 – 510 | 55 | Missing in isoform 3. | VSP_008085 | |||||
| Natural variant | 305 | 1 | H → P in PPNAD3; shows significantly higher cyclic AMP levels after transfection with the mutant protein than after transfection with the wild-type, indicating an impaired ability of the mutant protein to degrade cAMP. Ref.11 | VAR_066503 | |||||
Experimental info | |||||||||
| Sequence conflict | 147 | 1 | G → R in CAD38584. Ref.7 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Genomic organization, chromosomal localization, and alternative splicing of the human phosphodiesterase 8B gene." Hayashi M., Shimada Y., Nishimura Y., Hama T., Tanaka T. Biochem. Biophys. Res. Commun. 297:1253-1258(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 6), TISSUE SPECIFICITY. |
| [2] | "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in humans." Gamanuma M., Yuasa K., Sasaki T., Sakurai N., Kotera J., Omori K. Cell. Signal. 15:565-574(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Thyroid. |
| [3] | "Identification of a human proliferation-inducing gene." Kim J.W. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "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: Testis. |
| [6] | "Molecular cloning and characterization of human PDE8B, a novel thyroid-specific isozyme of 3',5'-cyclic nucleotide phosphodiesterase." Hayashi M., Matsushima K., Ohashi H., Tsunoda H., Murase S., Kawarada Y., Tanaka T. Biochem. Biophys. Res. Commun. 250:751-756(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 227-885 (ISOFORM 1). |
| [7] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 43-885 (ISOFORM 1). Tissue: Amygdala. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [9] | "Autosomal-dominant striatal degeneration is caused by a mutation in the phosphodiesterase 8B gene." Appenzeller S., Schirmacher A., Halfter H., Baumer S., Pendziwiat M., Timmerman V., De Jonghe P., Fekete K., Stogbauer F., Ludemann P., Hund M., Quabius E.S., Ringelstein E.B., Kuhlenbaumer G. Am. J. Hum. Genet. 86:83-87(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ADSD. |
| [10] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex." Horvath A., Giatzakis C., Tsang K., Greene E., Osorio P., Boikos S., Libe R., Patronas Y., Robinson-White A., Remmers E., Bertherat J., Nesterova M., Stratakis C.A. Eur. J. Hum. Genet. 16:1245-1253(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PPNAD3 PRO-305, CHARACTERIZATION OF VARIANT PPNAD3 PRO-305. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY129948 mRNA. Translation: AAN71723.1. AY129949 mRNA. Translation: AAN71724.1. AY129950 Genomic DNA. Translation: AAN71725.1. AY129950 Genomic DNA. Translation: AAN71726.1. AY129950 Genomic DNA. Translation: AAN71727.1. AB085824 mRNA. Translation: BAC53762.1. AB085825 mRNA. Translation: BAC53763.1. AB085826 mRNA. Translation: BAC53764.1. AB085827 mRNA. Translation: BAC53765.1. AY423729 mRNA. Translation: AAS00492.1. CH471084 Genomic DNA. Translation: EAW95803.1. BC043209 mRNA. No translation available. AF079529 mRNA. Translation: AAC69564.2. AL831924 mRNA. Translation: CAD38584.1. |
| IPI | IPI00216767. IPI00216768. IPI00294049. IPI00337505. IPI00337506. IPI00337507. |
| PIR | JE0293. |
| RefSeq | NP_001025022.1. NM_001029851.2. NP_001025023.1. NM_001029852.2. NP_001025024.1. NM_001029853.2. NP_001025025.1. NM_001029854.2. NP_003710.1. NM_003719.3. |
| UniGene | Hs.584830. |
3D structure databases | |
| ProteinModelPortal | O95263. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | 9606.ENSP00000264917. |
PTM databases | |
| PhosphoSite | O95263. |
2D gel databases | |
| UCD-2DPAGE | O95263. |
Proteomic databases | |
| PaxDb | O95263. |
| PRIDE | O95263. |
Protocols and materials databases | |
| DNASU | 8622. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000264917; ENSP00000264917; ENSG00000113231. ENST00000333194; ENSP00000331336; ENSG00000113231. ENST00000340978; ENSP00000345446; ENSG00000113231. ENST00000342343; ENSP00000345646; ENSG00000113231. ENST00000346042; ENSP00000330428; ENSG00000113231. ENST00000505283; ENSP00000423461; ENSG00000113231. |
| GeneID | 8622. |
| KEGG | hsa:8622. |
| UCSC | uc003kfa.3. human. uc003kfb.3. human. uc003kfc.3. human. uc003kfd.3. human. uc003kfe.3. human. |
Organism-specific databases | |
| CTD | 8622. |
| GeneCards | GC05P076542. |
| H-InvDB | HIX0004971. |
| HGNC | HGNC:8794. PDE8B. |
| HPA | HPA036912. |
| MIM | 603390. gene. 609161. phenotype. 614190. phenotype. |
| neXtProt | NX_O95263. |
| Orphanet | 228169. Autosomal dominant striatal neurodegeneration. 189439. Primary pigmented nodular adrenocortical disease. |
| PharmGKB | PA33142. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG282089. |
| HOVERGEN | HBG053544. |
| InParanoid | O95263. |
| KO | K01120. |
| OMA | LCCTTDN. |
| PhylomeDB | O95263. |
Enzyme and pathway databases | |
| Reactome | REACT_111102. Signal Transduction. |
| UniPathway | UPA00762; UER00747. |
Gene expression databases | |
| ArrayExpress | O95263. |
| Bgee | O95263. |
| CleanEx | HS_PDE8B. |
| Genevestigator | O95263. |
| GermOnline | ENSG00000113231. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.1300.10. 1 hit. |
| InterPro | IPR003607. HD/PDEase_dom. IPR000014. PAS. IPR023088. PDEase. IPR002073. PDEase_catalytic_dom. IPR023174. PDEase_CS. IPR013938. PDEase_PDE8. IPR001789. Sig_transdc_resp-reg_receiver. [Graphical view] |
| Pfam | PF08629. PDE8. 1 hit. PF00233. PDEase_I. 1 hit. PF00072. Response_reg. 1 hit. [Graphical view] |
| PRINTS | PR00387. PDIESTERASE1. |
| SMART | SM00471. HDc. 1 hit. SM00091. PAS. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR00229. sensory_box. 1 hit. |
| PROSITE | PS50112. PAS. 1 hit. PS00126. PDEASE_I. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | O95263. |
| ChEMBL | CHEMBL4408. |
| GenomeRNAi | 8622. |
| NextBio | 32309. |
| SOURCE | Search... |
Entry information
| Entry name | PDE8B_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O95263 Secondary accession number(s): Q5J7V7 Q8N3T2 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with
