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UniProtKB - Q08499 (PDE4D_HUMAN)

Entry version 219 (02 Dec 2020)
Sequence version 2 (01 Dec 2000)
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Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4D

Gene

PDE4D

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.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 cation2 PublicationsNote: 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.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 rolipram. Activated by phosphatidic acid.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'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. Phosphodiesterase, Phosphodiesterase (PDE4C), Phosphodiesterase (PDE4C), 3',5'-cyclic-AMP phosphodiesterase (PDE4B), Phosphodiesterase (PDE4D), Phosphodiesterase (PDE8A), Phosphodiesterase, Phosphodiesterase (PDE4B), Phosphodiesterase (PDE4C), Phosphodiesterase, Phosphodiesterase, 3',5'-cyclic-AMP phosphodiesterase (PDE4B), 3',5'-cyclic-AMP phosphodiesterase (PDE4D), Phosphodiesterase (PDE8B), 3',5'-cyclic-AMP phosphodiesterase (PDE4B), Phosphodiesterase (PDE4D), 3',5'-cyclic-AMP phosphodiesterase (PDE4DN2), Phosphodiesterase, cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), 3',5'-cyclic-AMP phosphodiesterase (HSPDE4D), Phosphodiesterase, Phosphodiesterase (PDE4C), Phosphodiesterase (PDE4D), Phosphodiesterase (PDE4C), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), Phosphodiesterase (PDE4C), Phosphodiesterase (PDE4D), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), 3',5'-cyclic-AMP phosphodiesterase (PDE4A), 3',5'-cyclic-AMP phosphodiesterase (PDE4B), Phosphodiesterase (PDE4B), 3',5'-cyclic-AMP phosphodiesterase (PDE4C), 3',5'-cyclic-AMP phosphodiesterase (PDE4A), Phosphodiesterase (PDE4C), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), 3',5'-cyclic-AMP phosphodiesterase (PDE4B), Phosphodiesterase, 3',5'-cyclic-AMP phosphodiesterase (PDE4C)
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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 sitei462Proton donorBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 bindingi466Divalent metal cation 11
Metal bindingi502Divalent metal cation 11
Metal bindingi503Divalent metal cation 11
Metal bindingi503Divalent metal cation 21
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei503cAMP2 Publications1
Metal bindingi620Divalent metal cation 11
Binding sitei620cAMP2 Publications1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei623Binds AMP, but not cAMP1
Binding sitei671cAMP2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi462 – 466cAMP2 Publications5

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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

More...BRENDAi		3.1.4.53, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q08499

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-180024, DARPP-32 events
R-HSA-418555, G alpha (s) signalling events

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q08499

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q08499

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%5Fand%5Ftaxonomy%5Fsection">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:
cAMP-specific 3',5'-cyclic phosphodiesterase 4D (EC:3.1.4.53)
Alternative name(s):
DPDE3
PDE43
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:PDE4D
Synonyms:DPDE3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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 5

Organism-specific databases

Eukaryotic Pathogen and Host Database Resources

More...EuPathDBi		HostDB:ENSG00000113448.16

Human Gene Nomenclature Database

More...HGNCi		HGNC:8783, PDE4D

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		600129, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q08499

<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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

<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

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.1 Publication
Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.
Related information in OMIM
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_068242190S → A in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514466EnsemblClinVar.1
Natural variantiVAR_068243225P → T in ACRDYS2. 2 PublicationsCorresponds to variant dbSNP:rs397514464EnsemblClinVar.1
Natural variantiVAR_068244226F → S in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514465EnsemblClinVar.1
Natural variantiVAR_069448227A → S in ACRDYS2. 1 Publication1
Natural variantiVAR_069449228Q → E in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514468EnsemblClinVar.1
Natural variantiVAR_069450301S → T in ACRDYS2. 1 Publication1
Natural variantiVAR_069451304A → V in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397515433EnsemblClinVar.1
Natural variantiVAR_069452329V → A in ACRDYS2. 1 Publication1
Natural variantiVAR_068245587T → P in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514467EnsemblClinVar.1
Natural variantiVAR_069453590E → A in ACRDYS2. 2 Publications1
Natural variantiVAR_069454673G → D in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514469EnsemblClinVar.1
Natural variantiVAR_069455678I → T in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs587777188EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi503D → N: Abolishes catalytic activity. 1
Mutagenesisi527D → R: Abolishes homodimerization. 1 Publication1
Mutagenesisi563R → D: Abolishes homodimerization. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		5144

MalaCards human disease database

More...MalaCardsi		PDE4D
MIMi614613, phenotype

Open Targets

More...OpenTargetsi		ENSG00000113448

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		950, Acrodysostosis
280651, Acrodysostosis with multiple hormone resistance
439822, PDE4D haploinsufficiency syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA33130

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q08499, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL288

Drug and drug target database

More...DrugBanki		DB06842, (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one
DB04149, (R)-Rolipram
DB03606, (S)-Rolipram
DB03183, 1-(4-Aminophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB04469, 1-(4-Methoxyphenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB02676, 2-[3-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Propylamino]-2-Hydroxymethyl-Propane-1,3-Diol
DB01959, 3,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB07051, 3,5-DIMETHYL-1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACID ETHYL ESTER
DB04271, 3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB07954, 3-isobutyl-1-methyl-7H-xanthine
DB08299, 4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid
DB00131, Adenosine phosphate
DB01427, Amrinone
DB00201, Caffeine
DB03849, Cilomilast
DB05219, Crisaborole
DB00651, Dyphylline
DB06246, Exisulind
DB05266, Ibudilast
DB01088, Iloprost
DB01791, Piclamilast
DB01656, Roflumilast
DB01954, Rolipram
DB05298, Tetomilast
DB09283, Trapidil
DB02918, Zardaverine

DrugCentral

More...DrugCentrali		Q08499

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1303

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		PDE4D

Domain mapping of disease mutations (DMDM)

More...DMDMi		12644392

<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 or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001988141 – 809cAMP-specific 3',5'-cyclic phosphodiesterase 4DAdd BLAST809

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 residuei142PhosphoserineBy similarity1
Modified residuei299PhosphoserineCombined sources1
Modified residuei301PhosphoserineCombined sources1
Modified residuei348PhosphoserineCombined sources1
Modified residuei375PhosphoserineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Isoform 3 (identifier: Q08499-2)
Modified residuei54Phosphoserine1 Publication1
Isoform 5 (identifier: Q08499-6)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Isoform N3 (identifier: Q08499-7)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Isoform 12 (identifier: Q08499-12)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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

Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation (By similarity). Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.By similarity
Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q08499

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q08499

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q08499

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

More...PaxDbi		Q08499

PeptideAtlas

More...PeptideAtlasi		Q08499

PRoteomics IDEntifications database

More...PRIDEi		Q08499

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		58620 [Q08499-1]
58621 [Q08499-10]
58622 [Q08499-11]
58623 [Q08499-12]
58624 [Q08499-2]
58625 [Q08499-3]
58626 [Q08499-4]
58627 [Q08499-5]
58628 [Q08499-6]
58629 [Q08499-7]
58630 [Q08499-8]
58631 [Q08499-9]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q08499

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

More...PhosphoSitePlusi		Q08499

<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 colonic epithelial cells (at protein level). Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000113448, Expressed in stomach and 228 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q08499, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q08499, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000113448, Tissue enhanced (skeletal)

<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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9.

Interacts with PDE4DIP.

Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12 bind RACK1 via their unique N-terminus. Binds ARRB2.

Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.

By similarity15 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		111170, 55 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q08499

Database of interacting proteins

More...DIPi		DIP-41115N

Protein interaction database and analysis system

More...IntActi		Q08499, 27 interactors

Molecular INTeraction database

More...MINTi		Q08499

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000345502

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q08499

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q08499, protein

<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

1809
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

More...SMRi		Q08499

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q08499

<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%5Fand%5Fdomains%5Fsection">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>Domaini386 – 715PDEasePROSITE-ProRule annotationAdd BLAST330

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi42 – 88Pro-richAdd BLAST47

<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

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3689, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000155674

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_005940_5_2_1

Identification of Orthologs from Complete Genome Data

More...OMAi		VNKWGLQ

Database of Orthologous Groups

More...OrthoDBi		67372at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q08499

TreeFam database of animal gene trees

More...TreeFami		TF314638

Family and domain databases

Conserved Domains Database

More...CDDi		cd00077, HDc, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.1300.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR003607, HD/PDEase_dom
IPR040844, PDE4_UCR
IPR023088, PDEase
IPR002073, PDEase_catalytic_dom
IPR036971, PDEase_catalytic_dom_sf
IPR023174, PDEase_CS

Pfam protein domain database

More...Pfami		View protein in Pfam
PF18100, PDE4_UCR, 1 hit
PF00233, PDEase_I, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00387, PDIESTERASE1

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
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%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (12+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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 12 <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. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 12 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 4 (identifier: Q08499-1) [UniParc]FASTAAdd to basket
Also known as: hPDE4D4

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL 
        60         70         80         90        100
LHPHHHLPPP PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA 
       110        120        130        140        150
TGRVRHRGYS DTERYLYCRA MDRTSYAVET GHRPGLKKSR MSWPSSFQGL 
       160        170        180        190        200
RRFDVDNGTS AGRSPLDPMT SPGSGLILQA NFVHSQRRES FLYRSDSDYD 
       210        220        230        240        250
LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF AALTNLQDRA 
       260        270        280        290        300
PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV 
       310        320        330        340        350
SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT 
       360        370        380        390        400
QKEKEKKKRP MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED 
       410        420        430        440        450
VNKWGLHVFR IAELSGNRPL TVIMHTIFQE RDLLKTFKIP VDTLITYLMT 
       460        470        480        490        500
LEDHYHADVA YHNNIHAADV VQSTHVLLST PALEAVFTDL EILAAIFASA 
       510        520        530        540        550
IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF KLLQEENCDI 
       560        570        580        590        600
FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL 
       610        620        630        640        650
LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER 
       660        670        680        690        700
ERGMEISPMC DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT 
       710        720        730        740        750
LEDNREWYQS TIPQSPSPAP DDPEEGRQGQ TEKFQFELTL EEDGESDTEK 
       760        770        780        790        800
DSGSQVEEDT SCSDSKTLCT QDSESTEIPL DEQVEEEAVG EEEESQPEAC 

VIDDRSPDT
Length:809
Mass (Da):91,115
Last modified:December 1, 2000 - 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:i7A4773DD3A044F57
GO
Isoform 3 (identifier: Q08499-2) [UniParc]FASTAAdd to basket
Also known as: hPDE4D3

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MMHVNNFPFRRHSWIC

Note: Activated by phosphorylation at Ser-53. Mutagenesis of Ser-54 abolishes activation.Curated
Show »
Length:673
Mass (Da):76,467
Checksum:iBDC04171BA91A297
GO
Isoform 10 (identifier: Q08499-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-205: Missing.

Show »
Length:604
Mass (Da):68,607
Checksum:i446D0C31C86399AB
GO
Isoform 1 (identifier: Q08499-4) [UniParc]FASTAAdd to basket
Also known as: hPDE4D1

The sequence of this isoform differs from the canonical sequence as follows:
     1-269: MEAEGSSAPA...QPSINKATIT → MKEQPSCAGT...TESPFPCLFA

Show »
Length:584
Mass (Da):66,376
Checksum:iC1761886FF962102
GO
Isoform 2 (identifier: Q08499-5) [UniParc]FASTAAdd to basket
Also known as: hPDE4D2

The sequence of this isoform differs from the canonical sequence as follows:
     1-302: Missing.

Show »
Length:507
Mass (Da):57,792
Checksum:i6C07C949952EE5DF
GO
Isoform 5 (identifier: Q08499-6) [UniParc]FASTAAdd to basket
Also known as: hPDE4D5

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC

Show »
Length:745
Mass (Da):84,428
Checksum:iD136AE2B7132DAAC
GO
Isoform N3 (identifier: Q08499-7) [UniParc]FASTAAdd to basket
Also known as: PDE4DN3

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-279: EEAYQKLASE → GLYNGIIAFL
     280-809: Missing.

Show »
Length:215
Mass (Da):23,839
Checksum:i255EF7985DB75353
GO
Isoform 6 (identifier: Q08499-8) [UniParc]FASTAAdd to basket
Also known as: PDE4D6

The sequence of this isoform differs from the canonical sequence as follows:
     1-291: Missing.
     292-306: ETLQTRHSVSEMASN → MPEANYLLSVSWGYI

Show »
Length:518
Mass (Da):59,113
Checksum:i069F18EB90BAAF4B
GO
Isoform 8 (identifier: Q08499-9) [UniParc]FASTAAdd to basket
Also known as: PDE4D8

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.
     123-152: RTSYAVETGHRPGLKKSRMSWPSSFQGLRR → MAFVWDPLGATVPGPSTRAKSRLRFSKSYS

Show »
Length:687
Mass (Da):77,705
Checksum:i90B1ED110D7ED77C
GO
Isoform 9 (identifier: Q08499-10) [UniParc]FASTAAdd to basket
Also known as: PDE4D9

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.
     131-152: GHRPGLKKSRMSWPSSFQGLRR → MSIIMKPRSRSTSSLRTAEAVC

Show »
Length:679
Mass (Da):76,816
Checksum:iD35B0A2D975C5705
GO
Isoform 7 (identifier: Q08499-11) [UniParc]FASTAAdd to basket
Also known as: PDE4D7

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
     62-152: PPSPQPQPQC...WPSSFQGLRR → MKRNTCDLLS...IAITSAESSG

Show »
Length:748
Mass (Da):84,662
Checksum:iD10CF5036B1EA7C8
GO
Isoform 12 (identifier: Q08499-12) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-283: EEAYQKLASETLEE → GSWMELNPYTLLDM
     284-809: Missing.

Show »
Length:219
Mass (Da):24,429
Checksum:i04C84B400D6F7D2C
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 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WSZ7A0A087WSZ7_HUMAN
Phosphodiesterase
PDE4D
678Annotation score:

Annotation score:3 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>
A0A1B0GW84A0A1B0GW84_HUMAN
Phosphodiesterase
PDE4D
699Annotation score:

Annotation score:3 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>
D6RHE0D6RHE0_HUMAN
Phosphodiesterase
PDE4D
422Annotation score:

Annotation score:3 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>
A0A1W2PQN6A0A1W2PQN6_HUMAN
3',5'-cyclic-AMP phosphodiesterase
PDE4D
125Annotation score:

Annotation score:2 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>
D6RAQ0D6RAQ0_HUMAN
cAMP-specific 3',5'-cyclic phosphod...
PDE4D
74Annotation 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>
D6RIG1D6RIG1_HUMAN
cAMP-specific 3',5'-cyclic phosphod...
PDE4D
81Annotation 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>
D6R9L4D6R9L4_HUMAN
cAMP-specific 3',5'-cyclic phosphod...
PDE4D
17Annotation 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>
D6RBB2D6RBB2_HUMAN
cAMP-specific 3',5'-cyclic phosphod...
PDE4D
29Annotation 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>

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 conflicti510S → F in AAH36319 (PubMed:15489334).Curated1
Sequence conflicti549D → G in AAN10119 (PubMed:12834813).Curated1
Sequence conflicti644R → P (PubMed:8797812).Curated1
Sequence conflicti769C → R in AAA97890 (PubMed:8125310).Curated1
Sequence conflicti769C → R in AAA97891 (PubMed:8125310).Curated1
Sequence conflicti769C → R in AAA97892 (PubMed:8125310).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068242190S → A in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514466EnsemblClinVar.1
Natural variantiVAR_068243225P → T in ACRDYS2. 2 PublicationsCorresponds to variant dbSNP:rs397514464EnsemblClinVar.1
Natural variantiVAR_068244226F → S in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514465EnsemblClinVar.1
Natural variantiVAR_069448227A → S in ACRDYS2. 1 Publication1
Natural variantiVAR_069449228Q → E in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514468EnsemblClinVar.1
Natural variantiVAR_069450301S → T in ACRDYS2. 1 Publication1
Natural variantiVAR_069451304A → V in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397515433EnsemblClinVar.1
Natural variantiVAR_069452329V → A in ACRDYS2. 1 Publication1
Natural variantiVAR_068245587T → P in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514467EnsemblClinVar.1
Natural variantiVAR_069453590E → A in ACRDYS2. 2 Publications1
Natural variantiVAR_069454673G → D in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514469EnsemblClinVar.1
Natural variantiVAR_069455678I → T in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs587777188EnsemblClinVar.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.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0045801 – 302Missing in isoform 2. 2 PublicationsAdd BLAST302
Alternative sequenceiVSP_0123831 – 291Missing in isoform 6. 2 PublicationsAdd BLAST291
Alternative sequenceiVSP_0045791 – 269MEAEG…KATIT → MKEQPSCAGTGHPMAGYGRM APFELASGPVKRLRTESPFP CLFA in isoform 1. 2 PublicationsAdd BLAST269
Alternative sequenceiVSP_0045781 – 205Missing in isoform 10. 2 PublicationsAdd BLAST205
Alternative sequenceiVSP_0045771 – 152MEAEG…QGLRR → MMHVNNFPFRRHSWIC in isoform 3. 2 PublicationsAdd BLAST152
Alternative sequenceiVSP_0123841 – 152MEAEG…QGLRR → MAQQTSPDTLTVPEVDNPHC PNPWLNEDLVKSLRENLLQH EKSKTARKSVSPKLSPVISP RNSPRLLRRMLLSSNIPKQR RFTVAHTC in isoform 5, isoform N3 and isoform 12. 4 PublicationsAdd BLAST152
Alternative sequenceiVSP_0123851 – 130Missing in isoform 9. 2 PublicationsAdd BLAST130
Alternative sequenceiVSP_0123861 – 122Missing in isoform 8. 1 PublicationAdd BLAST122
Alternative sequenceiVSP_0123871 – 61Missing in isoform 7. 2 PublicationsAdd BLAST61
Alternative sequenceiVSP_01238862 – 152PPSPQ…QGLRR → MKRNTCDLLSRSKSASEETL HSSNEEEDPFRGMEPYLVRR LSCRNIQLPPLAFRQLEQAD LKSESENIQRPTSLPLKILP LIAITSAESSG in isoform 7. 2 PublicationsAdd BLAST91
Alternative sequenceiVSP_012389123 – 152RTSYA…QGLRR → MAFVWDPLGATVPGPSTRAK SRLRFSKSYS in isoform 8. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_012390131 – 152GHRPG…QGLRR → MSIIMKPRSRSTSSLRTAEA VC in isoform 9. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_023326270 – 283EEAYQ…ETLEE → GSWMELNPYTLLDM in isoform 12. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_012391270 – 279EEAYQKLASE → GLYNGIIAFL in isoform N3. 1 Publication10
Alternative sequenceiVSP_012392280 – 809Missing in isoform N3. 1 PublicationAdd BLAST530
Alternative sequenceiVSP_023327284 – 809Missing in isoform 12. 2 PublicationsAdd BLAST526
Alternative sequenceiVSP_012393292 – 306ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 6. 2 PublicationsAdd BLAST15

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
L20970 mRNA Translation: AAA03592.1
L20969 mRNA Translation: AAC00042.1
U02882 mRNA Translation: AAC13745.1
U50157 mRNA Translation: AAA97890.1
U50158 mRNA Translation: AAA97891.1
U50159 mRNA Translation: AAA97892.1
AF012074 mRNA Translation: AAC00070.1
AF012073 mRNA Translation: AAC00069.1
AJ250854 mRNA Translation: CAC03757.1
AF536975 mRNA Translation: AAN10117.1
AF536976 mRNA Translation: AAN10118.1
AF536977 mRNA Translation: AAN10119.1
AY388960 mRNA Translation: AAQ90404.1
AY245866 mRNA Translation: AAP75760.1
AY245867 mRNA Translation: AAP75761.1
BT007398 mRNA Translation: AAP36062.1
BC008390 mRNA Translation: AAH08390.1
BC036319 mRNA Translation: AAH36319.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS47213.1 [Q08499-1]
CCDS54858.1 [Q08499-2]
CCDS54859.1 [Q08499-11]
CCDS56369.1 [Q08499-8]
CCDS56370.1 [Q08499-5]
CCDS56371.1 [Q08499-10]
CCDS56372.1 [Q08499-9]
CCDS56373.1 [Q08499-6]

Protein sequence database of the Protein Information Resource

More...PIRi		I61358

NCBI Reference Sequences

More...RefSeqi		NP_001098101.1, NM_001104631.1 [Q08499-1]
NP_001159371.1, NM_001165899.1 [Q08499-11]
NP_001184147.1, NM_001197218.1 [Q08499-6]
NP_001184148.1, NM_001197219.1 [Q08499-9]
NP_001184149.1, NM_001197220.1 [Q08499-10]
NP_001184150.1, NM_001197221.1 [Q08499-5]
NP_001184151.1, NM_001197222.1
NP_001184152.1, NM_001197223.1 [Q08499-8]
NP_006194.2, NM_006203.4 [Q08499-2]
XP_005248595.1, XM_005248538.4
XP_011541773.1, XM_011543471.1 [Q08499-11]
XP_011541775.1, XM_011543473.1 [Q08499-11]
XP_016865055.1, XM_017009566.1 [Q08499-11]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000309641; ENSP00000308485; ENSG00000113448 [Q08499-7]
ENST00000317118; ENSP00000321739; ENSG00000113448 [Q08499-8]
ENST00000340635; ENSP00000345502; ENSG00000113448 [Q08499-1]
ENST00000358923; ENSP00000351800; ENSG00000113448 [Q08499-5]
ENST00000360047; ENSP00000353152; ENSG00000113448 [Q08499-2]
ENST00000405755; ENSP00000384806; ENSG00000113448 [Q08499-9]
ENST00000502484; ENSP00000423094; ENSG00000113448 [Q08499-11]
ENST00000502575; ENSP00000425917; ENSG00000113448 [Q08499-12]
ENST00000503258; ENSP00000425605; ENSG00000113448 [Q08499-10]
ENST00000507116; ENSP00000424852; ENSG00000113448 [Q08499-6]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		5144

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:5144

UCSC genome browser

More...UCSCi		uc003jrs.4, human [Q08499-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) (PDE4D)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20970 mRNA Translation: AAA03592.1
L20969 mRNA Translation: AAC00042.1
U02882 mRNA Translation: AAC13745.1
U50157 mRNA Translation: AAA97890.1
U50158 mRNA Translation: AAA97891.1
U50159 mRNA Translation: AAA97892.1
AF012074 mRNA Translation: AAC00070.1
AF012073 mRNA Translation: AAC00069.1
AJ250854 mRNA Translation: CAC03757.1
AF536975 mRNA Translation: AAN10117.1
AF536976 mRNA Translation: AAN10118.1
AF536977 mRNA Translation: AAN10119.1
AY388960 mRNA Translation: AAQ90404.1
AY245866 mRNA Translation: AAP75760.1
AY245867 mRNA Translation: AAP75761.1
BT007398 mRNA Translation: AAP36062.1
BC008390 mRNA Translation: AAH08390.1
BC036319 mRNA Translation: AAH36319.1
CCDSiCCDS47213.1 [Q08499-1]
CCDS54858.1 [Q08499-2]
CCDS54859.1 [Q08499-11]
CCDS56369.1 [Q08499-8]
CCDS56370.1 [Q08499-5]
CCDS56371.1 [Q08499-10]
CCDS56372.1 [Q08499-9]
CCDS56373.1 [Q08499-6]
PIRiI61358
RefSeqiNP_001098101.1, NM_001104631.1 [Q08499-1]
NP_001159371.1, NM_001165899.1 [Q08499-11]
NP_001184147.1, NM_001197218.1 [Q08499-6]
NP_001184148.1, NM_001197219.1 [Q08499-9]
NP_001184149.1, NM_001197220.1 [Q08499-10]
NP_001184150.1, NM_001197221.1 [Q08499-5]
NP_001184151.1, NM_001197222.1
NP_001184152.1, NM_001197223.1 [Q08499-8]
NP_006194.2, NM_006203.4 [Q08499-2]
XP_005248595.1, XM_005248538.4
XP_011541773.1, XM_011543471.1 [Q08499-11]
XP_011541775.1, XM_011543473.1 [Q08499-11]
XP_016865055.1, XM_017009566.1 [Q08499-11]

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
1E9KNMR-A-[»]
1MKDX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L388-715[»]
1OYNX-ray2.00A/B/C/D381-740[»]
1PTWX-ray2.30A/B/C/D381-740[»]
1Q9MX-ray2.30A/B/C/D381-740[»]
1TB7X-ray1.63A/B388-715[»]
1TBBX-ray1.60A/B388-715[»]
1XOMX-ray1.55A/B388-715[»]
1XONX-ray1.72A/B388-715[»]
1XOQX-ray1.83A/B388-715[»]
1XORX-ray1.54A/B388-715[»]
1Y2BX-ray1.40A/B388-715[»]
1Y2CX-ray1.67A/B388-715[»]
1Y2DX-ray1.70A/B388-715[»]
1Y2EX-ray2.10A/B388-715[»]
1Y2KX-ray1.36A/B388-715[»]
1ZKNX-ray2.10A/B/C/D381-714[»]
2FM0X-ray2.00A/B/C/D381-741[»]
2FM5X-ray2.03A/B/C/D381-741[»]
2PW3X-ray1.56A/B388-714[»]
2QYNX-ray1.57A/B388-715[»]
3G4GX-ray2.30A/B/C/D299-347[»]
A/B/C/D360-714[»]
3G4IX-ray1.90A/B/C/D380-753[»]
3G4KX-ray1.95A/B/C/D380-753[»]
3G4LX-ray2.50A/B/C/D380-753[»]
3G58X-ray2.05A/B/C/D380-753[»]
3IADX-ray2.65A/B/C/D326-339[»]
A/B/C/D380-714[»]
3IAKX-ray2.80A388-715[»]
3K4SX-ray2.05A388-715[»]
3SL3X-ray2.10A/B/C/D381-741[»]
3SL4X-ray1.90A/B/C/D381-741[»]
3SL5X-ray2.65A/B/C/D381-714[»]
3SL6X-ray2.44A/B/C/D381-741[»]
3SL8X-ray2.60A/B/C/D381-741[»]
3V9BX-ray2.10A/B/C/D381-740[»]
4OGBX-ray2.03A/B/C/D381-741[»]
4W1OX-ray2.20A/B/C/D381-739[»]
4WCUX-ray2.35A/B/C/D381-739[»]
5K1IX-ray2.61A/B/C/D/E/F/G/H388-713[»]
5K32X-ray1.99A/B390-713[»]
5LBOX-ray2.25A/B/C/D381-740[»]
5TKBX-ray2.16A/B/C/D380-753[»]
5WH5X-ray1.80A/B388-714[»]
5WH6X-ray1.60A/B303-809[»]
5WQAX-ray2.30A/B381-714[»]
6AKRX-ray2.33A/B/C/D381-740[»]
6BOJX-ray1.70A/B/C/D380-718[»]
A/B/C/D730-734[»]
6F6UX-ray1.83A/B380-714[»]
6F8RX-ray1.83A/B380-714[»]
6F8TX-ray1.80A/B380-714[»]
6F8UX-ray2.10A/B380-714[»]
6F8VX-ray1.85A/B380-714[»]
6F8WX-ray1.60A/B380-714[»]
6F8XX-ray1.95A/B380-715[»]
6FDCX-ray1.45A/B380-714[»]
6FDIX-ray1.90A/B/C/D381-740[»]
6FE7X-ray2.00A/B/C/D381-740[»]
6FEBX-ray1.93A/B381-740[»]
6FETX-ray1.88A/B/C/D381-740[»]
6FT0X-ray2.10A/B/C/D381-740[»]
6FTAX-ray2.34A/B/C/D381-740[»]
6FTWX-ray2.16A/B/C/D381-740[»]
6FW3X-ray1.78A/B/C/D381-740[»]
6HWOX-ray1.99A/B/C/D381-740[»]
6IAGX-ray2.00A/B/C/D381-740[»]
6IBFX-ray2.31A/B/C/D381-740[»]
6IM6X-ray1.70A/B388-715[»]
6IMBX-ray1.55A/B388-715[»]
6IMDX-ray1.50A/B388-715[»]
6IMIX-ray1.46A/B388-715[»]
6IMOX-ray1.55A/B388-715[»]
6IMRX-ray1.50A/B388-715[»]
6IMTX-ray1.48A/B388-715[»]
6INDX-ray1.87A/B388-715[»]
6INKX-ray1.70A/B388-715[»]
6INMX-ray2.00A/B388-715[»]
6KJZX-ray2.20A/B387-714[»]
6KK0X-ray2.20A/B388-713[»]
6NJHX-ray2.15A/B/C/D326-339[»]
A/B/C/D380-718[»]
6NJIX-ray2.45A/B326-339[»]
A/B380-718[»]
6NJJX-ray2.30A/B/C/D326-339[»]
A/B/C/D380-718[»]
6RCWX-ray2.08A/B/C/D381-740[»]
SMRiQ08499
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi111170, 55 interactors
CORUMiQ08499
DIPiDIP-41115N
IntActiQ08499, 27 interactors
MINTiQ08499
STRINGi9606.ENSP00000345502

Chemistry databases

BindingDBiQ08499
ChEMBLiCHEMBL288
DrugBankiDB06842, (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one
DB04149, (R)-Rolipram
DB03606, (S)-Rolipram
DB03183, 1-(4-Aminophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB04469, 1-(4-Methoxyphenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB02676, 2-[3-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Propylamino]-2-Hydroxymethyl-Propane-1,3-Diol
DB01959, 3,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB07051, 3,5-DIMETHYL-1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACID ETHYL ESTER
DB04271, 3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester
DB07954, 3-isobutyl-1-methyl-7H-xanthine
DB08299, 4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid
DB00131, Adenosine phosphate
DB01427, Amrinone
DB00201, Caffeine
DB03849, Cilomilast
DB05219, Crisaborole
DB00651, Dyphylline
DB06246, Exisulind
DB05266, Ibudilast
DB01088, Iloprost
DB01791, Piclamilast
DB01656, Roflumilast
DB01954, Rolipram
DB05298, Tetomilast
DB09283, Trapidil
DB02918, Zardaverine
DrugCentraliQ08499
GuidetoPHARMACOLOGYi1303

PTM databases

iPTMnetiQ08499
PhosphoSitePlusiQ08499

Polymorphism and mutation databases

BioMutaiPDE4D
DMDMi12644392

Proteomic databases

jPOSTiQ08499
MassIVEiQ08499
MaxQBiQ08499
PaxDbiQ08499
PeptideAtlasiQ08499
PRIDEiQ08499
ProteomicsDBi58620 [Q08499-1]
58621 [Q08499-10]
58622 [Q08499-11]
58623 [Q08499-12]
58624 [Q08499-2]
58625 [Q08499-3]
58626 [Q08499-4]
58627 [Q08499-5]
58628 [Q08499-6]
58629 [Q08499-7]
58630 [Q08499-8]
58631 [Q08499-9]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		23607, 445 antibodies

The DNASU plasmid repository

More...DNASUi		5144

Genome annotation databases

EnsembliENST00000309641; ENSP00000308485; ENSG00000113448 [Q08499-7]
ENST00000317118; ENSP00000321739; ENSG00000113448 [Q08499-8]
ENST00000340635; ENSP00000345502; ENSG00000113448 [Q08499-1]
ENST00000358923; ENSP00000351800; ENSG00000113448 [Q08499-5]
ENST00000360047; ENSP00000353152; ENSG00000113448 [Q08499-2]
ENST00000405755; ENSP00000384806; ENSG00000113448 [Q08499-9]
ENST00000502484; ENSP00000423094; ENSG00000113448 [Q08499-11]
ENST00000502575; ENSP00000425917; ENSG00000113448 [Q08499-12]
ENST00000503258; ENSP00000425605; ENSG00000113448 [Q08499-10]
ENST00000507116; ENSP00000424852; ENSG00000113448 [Q08499-6]
GeneIDi5144
KEGGihsa:5144
UCSCiuc003jrs.4, human [Q08499-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		5144
DisGeNETi5144
EuPathDBiHostDB:ENSG00000113448.16

GeneCards: human genes, protein and diseases

More...GeneCardsi		PDE4D
HGNCiHGNC:8783, PDE4D
HPAiENSG00000113448, Tissue enhanced (skeletal)
MalaCardsiPDE4D
MIMi600129, gene
614613, phenotype
neXtProtiNX_Q08499
OpenTargetsiENSG00000113448
Orphaneti950, Acrodysostosis
280651, Acrodysostosis with multiple hormone resistance
439822, PDE4D haploinsufficiency syndrome
PharmGKBiPA33130

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3689, Eukaryota
GeneTreeiENSGT00940000155674
HOGENOMiCLU_005940_5_2_1
OMAiVNKWGLQ
OrthoDBi67372at2759
PhylomeDBiQ08499
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayiUPA00762;UER00747
BRENDAi3.1.4.53, 2681
PathwayCommonsiQ08499
ReactomeiR-HSA-180024, DARPP-32 events
R-HSA-418555, G alpha (s) signalling events
SignaLinkiQ08499
SIGNORiQ08499

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		5144, 8 hits in 845 CRISPR screens

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

More...ChiTaRSi		PDE4D, human
EvolutionaryTraceiQ08499

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		PDE4D

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

More...GenomeRNAii		5144
PharosiQ08499, Tclin

Protein Ontology

More...PROi		PR:Q08499
RNActiQ08499, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000113448, Expressed in stomach and 228 other tissues
ExpressionAtlasiQ08499, baseline and differential
GenevisibleiQ08499, HS

Family and domain databases

CDDicd00077, HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607, HD/PDEase_dom
IPR040844, PDE4_UCR
IPR023088, PDEase
IPR002073, PDEase_catalytic_dom
IPR036971, PDEase_catalytic_dom_sf
IPR023174, PDEase_CS
PfamiView protein in Pfam
PF18100, PDE4_UCR, 1 hit
PF00233, PDEase_I, 1 hit
PRINTSiPR00387, PDIESTERASE1
PROSITEiView protein in PROSITE
PS00126, PDEASE_I_1, 1 hit
PS51845, PDEASE_I_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		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 nameiPDE4D_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: Q08499
Secondary accession number(s): O43433
, Q13549, Q13550, Q13551, Q7Z2L8, Q8IV84, Q8IVA9, Q8IVD2, Q8IVD3, Q96HL4, Q9HCX7
<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%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 1, 2000
Last modified: December 2, 2020
This is version 219 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, Reference proteome

Documents

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