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Protein

High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A

Gene

PDE8A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

a divalent metal cation1 PublicationNote: 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.1 Publication

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and zaprinast as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: 3',5'-cyclic AMP degradation

This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
Proteins known to be involved in this subpathway in this organism are:
  1. High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B)
This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei556Proton donorBy similarity1
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi560Divalent metal cation 1; via tele nitrogenCombined sources1 PublicationImported1
Metal bindingi596Divalent metal cation 1; via tele nitrogenCombined sources1 PublicationImported1
Metal bindingi597Divalent metal cation 1Combined sources1 PublicationImported1
Metal bindingi597Divalent metal cation 2Combined sources1 PublicationImported1
Metal bindingi726Divalent metal cation 1Combined sources1 PublicationImported1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: UniProtKB
  • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB
  • kinase binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase
LigandcAMP, Metal-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
3.1.4.53 2681

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-418555 G alpha (s) signalling events

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00762;UER00747

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC:3.1.4.53By similarity)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:PDE8A
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000073417.14

Human Gene Nomenclature Database

More...
HGNCi
HGNC:8793 PDE8A

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602972 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O60658

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi454 – 455RR → AA: Reduces interaction with RAF1; when associated with A-460 and A-461. 1 Publication2
Mutagenesisi460 – 461EY → AA: Reduces interaction with RAF1; when associated with A-454 and A-455. 1 Publication2
Mutagenesisi748Y → F: Increases sensitivity to several nonselective or family selective PDE inhibitors. 1 Publication1

Organism-specific databases

DisGeNET

More...
DisGeNETi
5151

Open Targets

More...
OpenTargetsi
ENSG00000073417

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA33141

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL4640

Drug and drug target database

More...
DrugBanki
DB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1307

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
PDE8A

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001988381 – 829High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8AAdd BLAST829

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei20PhosphoserineCombined sources1
Modified residuei359Phosphoserine; by PKA1 Publication1
Modified residuei386PhosphoserineBy similarity1
Modified residuei457PhosphoserineCombined sources1
Modified residuei461PhosphotyrosineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated at Ser-359 by PKA under elevated cAMP conditions, this enhances catalytic activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O60658

MaxQB - The MaxQuant DataBase

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MaxQBi
O60658

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O60658

PeptideAtlas

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PeptideAtlasi
O60658

PRoteomics IDEntifications database

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PRIDEi
O60658

ProteomicsDB human proteome resource

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ProteomicsDBi
49499
49500 [O60658-2]
49501 [O60658-3]
49502 [O60658-4]
49503 [O60658-5]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O60658

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O60658

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in most tissues except thymus and peripheral blood leukocytes. Highest levels in testis, ovary, small intestine and colon.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000073417 Expressed in 231 organ(s), highest expression level in corpus callosum

CleanEx database of gene expression profiles

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CleanExi
HS_PDE8A

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O60658 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O60658 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA007722

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with RAF1. The interaction promotes RAF1 activity.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111177, 4 interactors

Protein interaction database and analysis system

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IntActi
O60658, 2 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000311453

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O60658

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1829
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O60658

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O60658

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O60658

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini213 – 283PASPROSITE-ProRule annotationAdd BLAST71
Domaini287 – 329PACAdd BLAST43
Domaini480 – 820PDEasePROSITE-ProRule annotationAdd BLAST341

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni454 – 461Involved in RAF1-binding1 Publication8

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1229 Eukaryota
ENOG410XP9B LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000156422

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG053544

KEGG Orthology (KO)

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KOi
K18437

Identification of Orthologs from Complete Genome Data

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OMAi
HYVSISR

Database of Orthologous Groups

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OrthoDBi
EOG091G0337

Database for complete collections of gene phylogenies

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PhylomeDBi
O60658

TreeFam database of animal gene trees

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TreeFami
TF314638

Family and domain databases

Conserved Domains Database

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CDDi
cd00077 HDc, 1 hit
cd00130 PAS, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.1300.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR003607 HD/PDEase_dom
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00989 PAS, 1 hit
PF00233 PDEase_I, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00387 PDIESTERASE1

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00471 HDc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF55785 SSF55785, 1 hit

TIGRFAMs; a protein family database

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TIGRFAMsi
TIGR00229 sensory_box, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50112 PAS, 1 hit
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 6 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 6 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60658-1) [UniParc]FASTAAdd to basket
Also known as: PDE8A1

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.

« Hide
        10         20         30         40         50
MGCAPSIHIS ERLVAEDAPS PAAPPLSSGG PRLPQGQKTA ALPRTRGAGL
60 70 80 90 100
LESELRDGSG KKVAVADVQF GPMRFHQDQL QVLLVFTKED NQCNGFCRAC
110 120 130 140 150
EKAGFKCTVT KEAQAVLACF LDKHHDIIII DHRNPRQLDA EALCRSIRSS
160 170 180 190 200
KLSENTVIVG VVRRVDREEL SVMPFISAGF TRRYVENPNI MACYNELLQL
210 220 230 240 250
EFGEVRSQLK LRACNSVFTA LENSEDAIEI TSEDRFIQYA NPAFETTMGY
260 270 280 290 300
QSGELIGKEL GEVPINEKKA DLLDTINSCI RIGKEWQGIY YAKKKNGDNI
310 320 330 340 350
QQNVKIIPVI GQGGKIRHYV SIIRVCNGNN KAEKISECVQ SDTHTDNQTG
360 370 380 390 400
KHKDRRKGSL DVKAVASRAT EVSSQRRHSS MARIHSMTIE APITKVINII
410 420 430 440 450
NAAQESSPMP VTEALDRVLE ILRTTELYSP QFGAKDDDPH ANDLVGGLMS
460 470 480 490 500
DGLRRLSGNE YVLSTKNTQM VSSNIITPIS LDDVPPRIAR AMENEEYWDF
510 520 530 540 550
DIFELEAATH NRPLIYLGLK MFARFGICEF LHCSESTLRS WLQIIEANYH
560 570 580 590 600
SSNPYHNSTH SADVLHATAY FLSKERIKET LDPIDEVAAL IAATIHDVDH
610 620 630 640 650
PGRTNSFLCN AGSELAILYN DTAVLESHHA ALAFQLTTGD DKCNIFKNME
660 670 680 690 700
RNDYRTLRQG IIDMVLATEM TKHFEHVNKF VNSINKPLAT LEENGETDKN
710 720 730 740 750
QEVINTMLRT PENRTLIKRM LIKCADVSNP CRPLQYCIEW AARISEEYFS
760 770 780 790 800
QTDEEKQQGL PVVMPVFDRN TCSIPKSQIS FIDYFITDMF DAWDAFVDLP
810 820
DLMQHLDNNF KYWKGLDEMK LRNLRPPPE
Length:829
Mass (Da):93,304
Last modified:September 19, 2002 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i99BD05EA185A42CD
GO
Isoform 2 (identifier: O60658-2) [UniParc]FASTAAdd to basket
Also known as: PDE8A2

The sequence of this isoform differs from the canonical sequence as follows:
     239-284: Missing.

Show »
Length:783
Mass (Da):88,293
Checksum:i67BB1FBE670D7EFE
GO
Isoform 3 (identifier: O60658-3) [UniParc]FASTAAdd to basket
Also known as: PDE8A3

The sequence of this isoform differs from the canonical sequence as follows:
     213-231: ACNSVFTALENSEDAIEIT → SGKEFTMQKRKTEIIYNKM
     232-829: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:231
Mass (Da):25,744
Checksum:iD7E21A8D19D661A6
GO
Isoform 4 (identifier: O60658-4) [UniParc]FASTAAdd to basket
Also known as: PDE8A4

The sequence of this isoform differs from the canonical sequence as follows:
     212-228: RACNSVFTALENSEDAI → SMQILHLKQQWAISQVN
     229-829: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:228
Mass (Da):25,279
Checksum:i4667A08AAA57F17F
GO
Isoform 5 (identifier: O60658-5) [UniParc]FASTAAdd to basket
Also known as: PDE8A5

The sequence of this isoform differs from the canonical sequence as follows:
     239-272: YANPAFETTMGYQSGELIGKELGEVPINEKKADL → PCCSSSWFGAAHIPSSAPVEVGVGLLPSWSLRRT
     273-829: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:272
Mass (Da):29,852
Checksum:iFEECE2A0C9115E13
GO
Isoform 6 (identifier: O60658-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.

Note: No experimental confirmation available.
Show »
Length:757
Mass (Da):86,049
Checksum:i66EB20F0822E42AC
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YKR1H0YKR1_HUMAN
High affinity cAMP-specific and IBM...
PDE8A
231Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PIJ0E9PIJ0_HUMAN
High affinity cAMP-specific and IBM...
PDE8A
272Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YNP3H0YNP3_HUMAN
High affinity cAMP-specific and IBM...
PDE8A
126Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAL18612 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence AAL18613 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence AAL18614 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence BAG54458 differs from that shown. Intron retention.Curated
The sequence EAX01967 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti55L → V in AAK57641 (PubMed:11371644).Curated1
Sequence conflicti344H → R in AAK57641 (PubMed:11371644).Curated1
Sequence conflicti344H → R in AAC39763 (PubMed:9618252).Curated1
Sequence conflicti399I → V in AAK57641 (PubMed:11371644).Curated1
Sequence conflicti399I → V in AAC39763 (PubMed:9618252).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_069109112E → G2 PublicationsCorresponds to variant dbSNP:rs17855018Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0460171 – 72Missing in isoform 6. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_041674212 – 228RACNS…SEDAI → SMQILHLKQQWAISQVN in isoform 4. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_041675213 – 231ACNSV…AIEIT → SGKEFTMQKRKTEIIYNKM in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_041676229 – 829Missing in isoform 4. 1 PublicationAdd BLAST601
Alternative sequenceiVSP_041677232 – 829Missing in isoform 3. 1 PublicationAdd BLAST598
Alternative sequenceiVSP_004597239 – 284Missing in isoform 2. 2 PublicationsAdd BLAST46
Alternative sequenceiVSP_041678239 – 272YANPA…KKADL → PCCSSSWFGAAHIPSSAPVE VGVGLLPSWSLRRT in isoform 5. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_041679273 – 829Missing in isoform 5. 1 PublicationAdd BLAST557

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF388183 mRNA Translation: AAL18610.1
AF388184 mRNA Translation: AAL18611.1
AF388185 mRNA Translation: AAL18612.1 Sequence problems.
AF388186 mRNA Translation: AAL18613.1 Sequence problems.
AF388187 mRNA Translation: AAL18614.1 Sequence problems.
AF332653 mRNA Translation: AAK57641.1
AK074280 mRNA No translation available.
AK127232 mRNA Translation: BAG54458.1 Sequence problems.
AC027078 Genomic DNA No translation available.
AC087468 Genomic DNA No translation available.
CH471101 Genomic DNA Translation: EAX01967.1 Sequence problems.
BC060762 mRNA Translation: AAH60762.1
BC075822 mRNA Translation: AAH75822.1
AF056490 mRNA Translation: AAC39763.1
AL109687 mRNA Translation: CAB52020.1
AL109778 mRNA Translation: CAB52432.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS10336.1 [O60658-1]
CCDS10337.1 [O60658-2]
CCDS58397.1 [O60658-6]

Protein sequence database of the Protein Information Resource

More...
PIRi
JW0088

NCBI Reference Sequences

More...
RefSeqi
NP_001230066.1, NM_001243137.1 [O60658-6]
NP_002596.1, NM_002605.2 [O60658-1]
NP_775656.1, NM_173454.1 [O60658-2]
XP_016877800.1, XM_017022311.1

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.9333

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000310298; ENSP00000311453; ENSG00000073417 [O60658-1]
ENST00000339708; ENSP00000340679; ENSG00000073417 [O60658-2]
ENST00000394553; ENSP00000378056; ENSG00000073417 [O60658-1]
ENST00000478717; ENSP00000432309; ENSG00000073417 [O60658-4]
ENST00000557957; ENSP00000453808; ENSG00000073417 [O60658-6]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
5151

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:5151

UCSC genome browser

More...
UCSCi
uc002blh.4 human [O60658-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF388183 mRNA Translation: AAL18610.1
AF388184 mRNA Translation: AAL18611.1
AF388185 mRNA Translation: AAL18612.1 Sequence problems.
AF388186 mRNA Translation: AAL18613.1 Sequence problems.
AF388187 mRNA Translation: AAL18614.1 Sequence problems.
AF332653 mRNA Translation: AAK57641.1
AK074280 mRNA No translation available.
AK127232 mRNA Translation: BAG54458.1 Sequence problems.
AC027078 Genomic DNA No translation available.
AC087468 Genomic DNA No translation available.
CH471101 Genomic DNA Translation: EAX01967.1 Sequence problems.
BC060762 mRNA Translation: AAH60762.1
BC075822 mRNA Translation: AAH75822.1
AF056490 mRNA Translation: AAC39763.1
AL109687 mRNA Translation: CAB52020.1
AL109778 mRNA Translation: CAB52432.1
CCDSiCCDS10336.1 [O60658-1]
CCDS10337.1 [O60658-2]
CCDS58397.1 [O60658-6]
PIRiJW0088
RefSeqiNP_001230066.1, NM_001243137.1 [O60658-6]
NP_002596.1, NM_002605.2 [O60658-1]
NP_775656.1, NM_173454.1 [O60658-2]
XP_016877800.1, XM_017022311.1
UniGeneiHs.9333

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LHQmodel-A482-821[»]
1LXXmodel-A488-821[»]
3ECMX-ray1.90A482-819[»]
3ECNX-ray2.10A/B482-819[»]
ProteinModelPortaliO60658
SMRiO60658
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111177, 4 interactors
IntActiO60658, 2 interactors
STRINGi9606.ENSP00000311453

Chemistry databases

BindingDBiO60658
ChEMBLiCHEMBL4640
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine
GuidetoPHARMACOLOGYi1307

PTM databases

iPTMnetiO60658
PhosphoSitePlusiO60658

Polymorphism and mutation databases

BioMutaiPDE8A

Proteomic databases

EPDiO60658
MaxQBiO60658
PaxDbiO60658
PeptideAtlasiO60658
PRIDEiO60658
ProteomicsDBi49499
49500 [O60658-2]
49501 [O60658-3]
49502 [O60658-4]
49503 [O60658-5]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310298; ENSP00000311453; ENSG00000073417 [O60658-1]
ENST00000339708; ENSP00000340679; ENSG00000073417 [O60658-2]
ENST00000394553; ENSP00000378056; ENSG00000073417 [O60658-1]
ENST00000478717; ENSP00000432309; ENSG00000073417 [O60658-4]
ENST00000557957; ENSP00000453808; ENSG00000073417 [O60658-6]
GeneIDi5151
KEGGihsa:5151
UCSCiuc002blh.4 human [O60658-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
5151
DisGeNETi5151
EuPathDBiHostDB:ENSG00000073417.14

GeneCards: human genes, protein and diseases

More...
GeneCardsi
PDE8A

H-Invitational Database, human transcriptome db

More...
H-InvDBi
HIX0012539
HGNCiHGNC:8793 PDE8A
HPAiHPA007722
MIMi602972 gene
neXtProtiNX_O60658
OpenTargetsiENSG00000073417
PharmGKBiPA33141

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1229 Eukaryota
ENOG410XP9B LUCA
GeneTreeiENSGT00940000156422
HOVERGENiHBG053544
KOiK18437
OMAiHYVSISR
OrthoDBiEOG091G0337
PhylomeDBiO60658
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayi
UPA00762;UER00747

BRENDAi3.1.4.53 2681
ReactomeiR-HSA-418555 G alpha (s) signalling events

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
PDE8A human
EvolutionaryTraceiO60658

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
PDE8A

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
5151

Protein Ontology

More...
PROi
PR:O60658

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000073417 Expressed in 231 organ(s), highest expression level in corpus callosum
CleanExiHS_PDE8A
ExpressionAtlasiO60658 baseline and differential
GenevisibleiO60658 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
cd00130 PAS, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00989 PAS, 1 hit
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
SUPFAMiSSF55785 SSF55785, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50112 PAS, 1 hit
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiPDE8A_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O60658
Secondary accession number(s): B3KXE6
, H0YMZ7, Q6P9H3, Q969I1, Q96PC9, Q96PD0, Q96PD1, Q96T71, Q9UMB7, Q9UMC3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2002
Last modified: December 5, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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