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UniProtKB - O76074 (PDE5A_HUMAN)

Entry version 192 (22 Apr 2020)
Sequence version 2 (11 Jan 2011)
Previous versions | rss
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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

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

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).2 Publications

Caution

Was initially thought to act as a major regulator of cardiac hypertrophy in myocytes and muscle and investigations have been made on selective PDE5A inhibitors that could protect against cardiovascular disease. However, while PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signaling is often depressed by heart disease, limiting its effect. Moreover, clinical trial using PDE5A inhibitors were disappointing.1 Publication

<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

Protein has several cofactor binding sites:

<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

Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast.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 GMP degradation

This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (PDE9A)
This subpathway is part of the pathway 3',5'-cyclic GMP 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 GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP 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 sitei613Proton 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 bindingi617Zinc; via tele nitrogen1 Publication1
Metal bindingi653Zinc; via tele nitrogen1 Publication1
Metal bindingi654Magnesium1 Publication1
Metal bindingi654Zinc1 Publication1
Metal bindingi764Zinc1 Publication1
<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 sitei817cGMP1 Publication1

<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 functionAllosteric enzyme, Hydrolase
LigandcGMP, cGMP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		3.1.4.35 2681

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-418457 cGMP effects

SIGNOR Signaling Network Open Resource

More...SIGNORi		O76074

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

More...UniPathwayi		UPA00763;UER00748

<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:
cGMP-specific 3',5'-cyclic phosphodiesterase (EC:3.1.4.351 Publication)
Alternative name(s):
cGMP-binding cGMP-specific phosphodiesterase
Short name:
CGB-PDE
<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:PDE5A
Synonyms:PDE5
<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 4

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:8784 PDE5A

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603310 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O76074

<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

<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

Organism-specific databases

DisGeNET

More...DisGeNETi		8654

Open Targets

More...OpenTargetsi		ENSG00000138735

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA33132

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O76074 Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1827

Drug and drug target database

More...DrugBanki		DB07954 3-isobutyl-1-methyl-7H-xanthine
DB08729 5-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamide
DB06237 Avanafil
DB00201 Caffeine
DB04272 Citric acid
DB00975 Dipyridamole
DB06246 Exisulind
DB12010 Fostamatinib
DB03597 gamma-Glutamyl[S-(2-iodobenzyl)cysteinyl]glycine
DB01972 Guanosine-5'-Monophosphate
DB09282 Molsidomine
DB05415 OSI-461
DB00806 Pentoxifylline
DB00203 Sildenafil
DB00820 Tadalafil
DB00277 Theophylline
DB09283 Trapidil
DB06267 Udenafil
DB00862 Vardenafil

DrugCentral

More...DrugCentrali		O76074

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1304

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		PDE5A

<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_00001988231 – 875cGMP-specific 3',5'-cyclic phosphodiesteraseAdd BLAST875

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 residuei102PhosphoserineSequence analysis1

<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

Phosphorylation is regulated by binding of cGMP to the two allosteric sites (By similarity). Phosphorylation by PRKG1 leads to its activation.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		O76074

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O76074

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O76074

MaxQB - The MaxQuant DataBase

More...MaxQBi		O76074

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

More...PaxDbi		O76074

PeptideAtlas

More...PeptideAtlasi		O76074

PRoteomics IDEntifications database

More...PRIDEi		O76074

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		50374 [O76074-1]
50375 [O76074-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O76074

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

More...PhosphoSitePlusi		O76074

<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 aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000138735 Expressed in intestine and 188 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O76074 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O76074 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000138735 Low tissue specificity

<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%27">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

Show more details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		114205, 8 interactors

Database of interacting proteins

More...DIPi		DIP-46287N

Protein interaction database and analysis system

More...IntActi		O76074, 6 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000347046

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O76074

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O76074 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

1875
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		O76074

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		O76074

<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>Domaini164 – 314GAF 1Add BLAST151
Domaini346 – 503GAF 2Add BLAST158
Domaini536 – 860PDEasePROSITE-ProRule annotationAdd BLAST325

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 biasi10 – 24Poly-GlnAdd BLAST15

<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 which contains two homologous allosteric cGMP-binding regions, A and B.

<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.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3689 Eukaryota
ENOG410XRI7 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000155475

KEGG Orthology (KO)

More...KOi		K13762

Identification of Orthologs from Complete Genome Data

More...OMAi		DQLPMMQ

Database of Orthologous Groups

More...OrthoDBi		904682at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O76074

TreeFam database of animal gene trees

More...TreeFami		TF316499

Family and domain databases

Conserved Domains Database

More...CDDi		cd00077 HDc, 1 hit

Database of protein disorder

More...DisProti		DP01244

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.1300.10, 1 hit
3.30.450.40, 2 hits

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR003018 GAF
IPR029016 GAF-like_dom_sf
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS

Pfam protein domain database

More...Pfami		View protein in Pfam
PF01590 GAF, 2 hits
PF00233 PDEase_I, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00387 PDIESTERASE1

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00065 GAF, 2 hits
SM00471 HDc, 1 hit

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 (2+)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 2 <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 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform PDE5A1 (identifier: O76074-1) [UniParc]FASTAAdd to basket

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
MERAGPSFGQ QRQQQQPQQQ KQQQRDQDSV EAWLDDHWDF TFSYFVRKAT 
        60         70         80         90        100
REMVNAWFAE RVHTIPVCKE GIRGHTESCS CPLQQSPRAD NSAPGTPTRK 
       110        120        130        140        150
ISASEFDRPL RPIVVKDSEG TVSFLSDSEK KEQMPLTPPR FDHDEGDQCS 
       160        170        180        190        200
RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSNDKFL 
       210        220        230        240        250
ISRLFDVAEG STLEEVSNNC IRLEWNKGIV GHVAALGEPL NIKDAYEDPR 
       260        270        280        290        300
FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE 
       310        320        330        340        350
KDFAAYLAFC GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI 
       360        370        380        390        400
LKKIAATIIS FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR 
       410        420        430        440        450
EHDANKINYM YAQYVKNTME PLNIPDVSKD KRFPWTTENT GNVNQQCIRS 
       460        470        480        490        500
LLCTPIKNGK KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ FLEAFVIFCG 
       510        520        530        540        550
LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL QSLAAAVVPS 
       560        570        580        590        600
AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL 
       610        620        630        640        650
SVKKNYRKNV AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA 
       660        670        680        690        700
LSHDLDHRGV NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI 
       710        720        730        740        750
LSGLSIEEYK TTLKIIKQAI LATDLALYIK RRGEFFELIR KNQFNLEDPH 
       760        770        780        790        800
QKELFLAMLM TACDLSAITK PWPIQQRIAE LVATEFFDQG DRERKELNIE 
       810        820        830        840        850
PTDLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR 
       860        870 
QKWQALAEQQ EKMLINGESG QAKRN
Length:875
Mass (Da):99,985
Last modified:January 11, 2011 - 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:i9E30C6C182F13388
GO
Isoform PDE5A2 (identifier: O76074-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKA → MLPFGDK

Show »
Length:833
Mass (Da):94,805
Checksum:i41D0B4B1BAB57D6D
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
G5E9C5G5E9C5_HUMAN
Phosphodiesterase
PDE5A hCG_38154
823Annotation 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>
H0YA14H0YA14_HUMAN
cGMP-specific 3',5'-cyclic phosphod...
PDE5A
185Annotation 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>
C9JGT3C9JGT3_HUMAN
cGMP-specific 3',5'-cyclic phosphod...
PDE5A
224Annotation 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 conflicti159I → V in AAP31235 (PubMed:10393044).Curated1
Sequence conflicti310C → G in AAP31235 (PubMed:10393044).Curated1
Sequence conflicti381S → F in AAP31235 (PubMed:10393044).Curated1
Sequence conflicti406K → R in AAP31235 (PubMed:10393044).Curated1
Sequence conflicti642E → G in BAA81667 (Ref. 4) 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_02777593A → V5 PublicationsCorresponds to variant dbSNP:rs3733526Ensembl.1
Natural variantiVAR_027776181S → A. Corresponds to variant dbSNP:rs17051276Ensembl.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_0045911 – 49MERAG…FVRKA → MLPFGDK in isoform PDE5A2. 3 PublicationsAdd BLAST49

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
AF043731 mRNA Translation: AAC63967.1
AF043732 mRNA Translation: AAC63968.1
AB001635 Genomic DNA Translation: BAA33372.2
D89094 mRNA Translation: BAA28945.1
AJ004865 mRNA Translation: CAA06170.1
AB015656 mRNA Translation: BAA81667.1
AY264918 mRNA Translation: AAP21809.1
AK290189 mRNA Translation: BAF82878.1
AC093752 Genomic DNA No translation available.
AC080089 Genomic DNA No translation available.
BC126233 mRNA Translation: AAI26234.1
AY266363 mRNA Translation: AAP31235.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS34055.1 [O76074-2]
CCDS3713.1 [O76074-1]

Protein sequence database of the Protein Information Resource

More...PIRi		JW0106

NCBI Reference Sequences

More...RefSeqi		NP_001074.2, NM_001083.3 [O76074-1]
NP_236914.2, NM_033430.2 [O76074-2]
NP_246273.2, NM_033437.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000264805; ENSP00000264805; ENSG00000138735 [O76074-2]
ENST00000354960; ENSP00000347046; ENSG00000138735 [O76074-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		8654

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:8654

UCSC genome browser

More...UCSCi		uc003idf.4 human [O76074-1]

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
AF043731 mRNA Translation: AAC63967.1
AF043732 mRNA Translation: AAC63968.1
AB001635 Genomic DNA Translation: BAA33372.2
D89094 mRNA Translation: BAA28945.1
AJ004865 mRNA Translation: CAA06170.1
AB015656 mRNA Translation: BAA81667.1
AY264918 mRNA Translation: AAP21809.1
AK290189 mRNA Translation: BAF82878.1
AC093752 Genomic DNA No translation available.
AC080089 Genomic DNA No translation available.
BC126233 mRNA Translation: AAI26234.1
AY266363 mRNA Translation: AAP31235.1
CCDSiCCDS34055.1 [O76074-2]
CCDS3713.1 [O76074-1]
PIRiJW0106
RefSeqiNP_001074.2, NM_001083.3 [O76074-1]
NP_236914.2, NM_033430.2 [O76074-2]
NP_246273.2, NM_033437.3

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
1RKPX-ray2.05A535-860[»]
1T9RX-ray2.10A531-875[»]
1T9SX-ray2.00A/B534-858[»]
1TBFX-ray1.30A534-858[»]
1UDTX-ray2.30A537-860[»]
1UDUX-ray2.83A/B537-860[»]
1UHOX-ray2.50A537-860[»]
1XOZX-ray1.37A534-875[»]
1XP0X-ray1.79A534-875[»]
2CHMX-ray1.60A534-656[»]
A682-858[»]
2H40X-ray1.85A535-860[»]
2H42X-ray2.30A/B/C535-860[»]
2H44X-ray1.80A535-860[»]
2XSSX-ray2.50A/B346-509[»]
3B2RX-ray2.07A/B535-860[»]
3BJCX-ray2.00A1-875[»]
3HC8X-ray1.79A536-657[»]
A682-858[»]
3HDZX-ray1.80A536-657[»]
A682-858[»]
3JWQX-ray2.87A/B/C/D535-786[»]
A/B/C/D827-860[»]
3JWRX-ray2.99A/B535-786[»]
A/B827-860[»]
3LFVX-ray2.80A/B98-518[»]
3MF0X-ray3.10A/B89-518[»]
3SHYX-ray2.65A535-860[»]
3SHZX-ray2.45A535-860[»]
3SIEX-ray1.93A/B535-860[»]
3TGEX-ray1.96A534-656[»]
A682-858[»]
3TGGX-ray1.91A534-660[»]
A662-858[»]
4G2WX-ray2.28A535-860[»]
4G2YX-ray2.40A535-860[»]
4I9ZX-ray2.08A535-860[»]
4IA0X-ray2.17A535-860[»]
4MD6X-ray2.00A535-860[»]
4OEWX-ray2.44A535-860[»]
4OEXX-ray2.14A535-860[»]
5JO3X-ray1.49B534-858[»]
5ZZ2X-ray2.60A535-860[»]
6ACBX-ray2.80A535-860[»]
6IWIX-ray2.15A535-860[»]
SMRiO76074
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi114205, 8 interactors
DIPiDIP-46287N
IntActiO76074, 6 interactors
STRINGi9606.ENSP00000347046

Chemistry databases

BindingDBiO76074
ChEMBLiCHEMBL1827
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB08729 5-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamide
DB06237 Avanafil
DB00201 Caffeine
DB04272 Citric acid
DB00975 Dipyridamole
DB06246 Exisulind
DB12010 Fostamatinib
DB03597 gamma-Glutamyl[S-(2-iodobenzyl)cysteinyl]glycine
DB01972 Guanosine-5'-Monophosphate
DB09282 Molsidomine
DB05415 OSI-461
DB00806 Pentoxifylline
DB00203 Sildenafil
DB00820 Tadalafil
DB00277 Theophylline
DB09283 Trapidil
DB06267 Udenafil
DB00862 Vardenafil
DrugCentraliO76074
GuidetoPHARMACOLOGYi1304

PTM databases

iPTMnetiO76074
PhosphoSitePlusiO76074

Polymorphism and mutation databases

BioMutaiPDE5A

Proteomic databases

EPDiO76074
jPOSTiO76074
MassIVEiO76074
MaxQBiO76074
PaxDbiO76074
PeptideAtlasiO76074
PRIDEiO76074
ProteomicsDBi50374 [O76074-1]
50375 [O76074-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		1386 162 antibodies

The DNASU plasmid repository

More...DNASUi		8654

Genome annotation databases

EnsembliENST00000264805; ENSP00000264805; ENSG00000138735 [O76074-2]
ENST00000354960; ENSP00000347046; ENSG00000138735 [O76074-1]
GeneIDi8654
KEGGihsa:8654
UCSCiuc003idf.4 human [O76074-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		8654
DisGeNETi8654

GeneCards: human genes, protein and diseases

More...GeneCardsi		PDE5A
HGNCiHGNC:8784 PDE5A
HPAiENSG00000138735 Low tissue specificity
MIMi603310 gene
neXtProtiNX_O76074
OpenTargetsiENSG00000138735
PharmGKBiPA33132

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00940000155475
KOiK13762
OMAiDQLPMMQ
OrthoDBi904682at2759
PhylomeDBiO76074
TreeFamiTF316499

Enzyme and pathway databases

UniPathwayiUPA00763;UER00748
BRENDAi3.1.4.35 2681
ReactomeiR-HSA-418457 cGMP effects
SIGNORiO76074

Miscellaneous databases

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

More...ChiTaRSi		PDE5A human
EvolutionaryTraceiO76074

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		CGMP-specific_phosphodiesterase_type_5

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

More...GenomeRNAii		8654
PharosiO76074 Tclin

Protein Ontology

More...PROi		PR:O76074
RNActiO76074 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000138735 Expressed in intestine and 188 other tissues
ExpressionAtlasiO76074 baseline and differential
GenevisibleiO76074 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
DisProtiDP01244
Gene3Di1.10.1300.10, 1 hit
3.30.450.40, 2 hits
InterProiView protein in InterPro
IPR003018 GAF
IPR029016 GAF-like_dom_sf
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF01590 GAF, 2 hits
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00065 GAF, 2 hits
SM00471 HDc, 1 hit
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 nameiPDE5A_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: O76074
Secondary accession number(s): A0AV69
, A8K2C4, O75026, O75887, Q86UI0, Q86V66, Q9Y6Z6
<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: July 15, 1999
Last sequence update: January 11, 2011
Last modified: April 22, 2020
This is version 192 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. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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