UniProtKB - O76074 (PDE5A_HUMAN)

BLAST

>sp|O76074|PDE5A_HUMAN cGMP-specific 3',5'-cyclic phosphodiesterase OS=Homo sapiens OX=9606 GN=PDE5A PE=1 SV=2
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG
TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI
SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL
NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE
KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS
FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME
PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK
VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL
QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL
SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV
NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI
LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE
LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF
PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN

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History
Entry version 181 (07 Nov 2018)
Sequence version 2 (11 Jan 2011)
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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

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

Catalytic activityⁱ

Guanosine 3',5'-cyclic phosphate + H₂O = guanosine 5'-phosphate.1 Publication

Cofactorⁱ

Protein has several cofactor binding sites:

Activity regulationⁱ

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:

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (PDE9A), cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)

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 key	Position(s)	DescriptionActions	Length
Active siteⁱ	613	Proton donorBy similarity	1
Metal bindingⁱ	617	Zinc; via tele nitrogen1 Publication	1
Metal bindingⁱ	653	Zinc; via tele nitrogen1 Publication	1
Metal bindingⁱ	654	Magnesium1 Publication	1
Metal bindingⁱ	654	Zinc1 Publication	1
Metal bindingⁱ	764	Zinc1 Publication	1
Binding siteⁱ	817	cGMP1 Publication	1

GO - Molecular functionⁱ

3',5'-cyclic-GMP phosphodiesterase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 14687666
3',5'-cyclic-nucleotide phosphodiesterase activity
Source: UniProtKB
Non-traceable author statementⁱ
- 9714779
cGMP binding
Source: UniProtKB
Traceable author statementⁱ
- 15938621
metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cGMP catabolic process Source: UniProtKB-UniPathway
negative regulation of cardiac muscle contraction Source: Ensembl
negative regulation of T cell proliferation Source: Ensembl
positive regulation of cardiac muscle hypertrophy Source: Ensembl
positive regulation of MAP kinase activity Source: Ensembl
positive regulation of oocyte development Source: Ensembl
regulation of nitric oxide mediated signal transduction Source: Ensembl
relaxation of cardiac muscle Source: Ensembl
signal transduction Source: InterPro

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Allosteric enzyme, Hydrolase
Ligand	cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	3.1.4.35 2681
Reactomeⁱ	R-HSA-418457 cGMP effects
SIGNORⁱ	O76074
UniPathwayⁱ	UPA00763;UER00748

Names & Taxonomyⁱ

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
Gene namesⁱ	Name:PDE5A Synonyms:PDE5
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 4

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000138735.15
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:8784 PDE5A
MIMⁱ	603310 gene
neXtProtⁱ	NX_O76074

Subcellular locationⁱ

GO - Cellular component

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	8654
Open Targets More...OpenTargetsⁱ	ENSG00000138735
PharmGKBⁱ	PA33132

Chemistry databases

ChEMBLⁱ	CHEMBL1827
Drug and drug target database More...DrugBankⁱ	DB07954 3-isobutyl-1-methyl-7H-xanthine DB06237 Avanafil DB00201 Caffeine DB04272 Citric Acid DB00975 Dipyridamole DB03597 Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine DB01972 Guanosine-5'-Monophosphate DB05415 OSI-461 DB00806 Pentoxifylline DB00203 Sildenafil DB00820 Tadalafil DB00277 Theophylline DB06267 Udenafil DB00862 Vardenafil
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1304

Polymorphism and mutation databases

BioMutaⁱ	PDE5A

BioMutaⁱ

PDE5A

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000198823	1 – 875	cGMP-specific 3',5'-cyclic phosphodiesteraseAdd BLAST		875

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	102	PhosphoserineSequence analysis		1

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

EPDⁱ	O76074
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O76074
PaxDbⁱ	O76074
PeptideAtlas More...PeptideAtlasⁱ	O76074
PRIDEⁱ	O76074
ProteomicsDBⁱ	50374 50375 [O76074-2]

PTM databases

iPTMnetⁱ	O76074
PhosphoSitePlusⁱ	O76074

Expressionⁱ

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

Bgeeⁱ	ENSG00000138735 Expressed in 189 organ(s), highest expression level in intestine
CleanExⁱ	HS_PDE5A
ExpressionAtlasⁱ	O76074 baseline and differential
Genevisibleⁱ	O76074 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA004729 HPA012873

HPAⁱ

HPA004729
HPA012873

Interactionⁱ

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
PRKG1	Q13976	4	EBI-9023531,EBI-3952014

With

Entry

#Exp.

IntAct

Notes

PRKG1

Q13976

EBI-9023531,EBI-3952014

Protein-protein interaction databases

BioGridⁱ	114205, 8 interactors
Database of interacting proteins More...DIPⁱ	DIP-46287N
IntActⁱ	O76074, 5 interactors
STRINGⁱ	9606.ENSP00000347046

Chemistry databases

BindingDBⁱ

O76074

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	103 – 106	Combined sources	4
Beta strandⁱ	115 – 117	Combined sources	3
Turnⁱ	118 – 120	Combined sources	3
Beta strandⁱ	121 – 124	Combined sources	4
Helixⁱ	148 – 160	Combined sources	13
Helixⁱ	165 – 177	Combined sources	13
Beta strandⁱ	182 – 192	Combined sources	11
Beta strandⁱ	198 – 205	Combined sources	8
Beta strandⁱ	208 – 210	Combined sources	3
Beta strandⁱ	213 – 218	Combined sources	6
Beta strandⁱ	221 – 224	Combined sources	4
Helixⁱ	228 – 236	Combined sources	9
Beta strandⁱ	240 – 243	Combined sources	4
Helixⁱ	245 – 247	Combined sources	3
Helixⁱ	254 – 259	Combined sources	6
Beta strandⁱ	266 – 272	Combined sources	7
Beta strandⁱ	278 – 287	Combined sources	10
Helixⁱ	299 – 340	Combined sources	42
Turnⁱ	342 – 345	Combined sources	4
Helixⁱ	346 – 362	Combined sources	17
Beta strandⁱ	365 – 372	Combined sources	8
Beta strandⁱ	374 – 376	Combined sources	3
Beta strandⁱ	379 – 387	Combined sources	9
Turnⁱ	388 – 390	Combined sources	3
Beta strandⁱ	391 – 393	Combined sources	3
Helixⁱ	400 – 403	Combined sources	4
Helixⁱ	407 – 409	Combined sources	3
Helixⁱ	410 – 418	Combined sources	9
Beta strandⁱ	422 – 425	Combined sources	4
Turnⁱ	427 – 429	Combined sources	3
Beta strandⁱ	431 – 433	Combined sources	3
Beta strandⁱ	451 – 457	Combined sources	7
Beta strandⁱ	461 – 471	Combined sources	11
Turnⁱ	476 – 478	Combined sources	3
Helixⁱ	486 – 506	Combined sources	21
Helixⁱ	535 – 545	Combined sources	11
Helixⁱ	551 – 554	Combined sources	4
Turnⁱ	555 – 557	Combined sources	3
Helixⁱ	568 – 581	Combined sources	14
Helixⁱ	584 – 587	Combined sources	4
Helixⁱ	592 – 604	Combined sources	13
Turnⁱ	606 – 608	Combined sources	3
Beta strandⁱ	610 – 614	Combined sources	5
Helixⁱ	615 – 630	Combined sources	16
Turnⁱ	631 – 633	Combined sources	3
Helixⁱ	635 – 637	Combined sources	3
Helixⁱ	640 – 652	Combined sources	13
Turnⁱ	653 – 656	Combined sources	4
Helixⁱ	662 – 667	Combined sources	6
Helixⁱ	671 – 675	Combined sources	5
Beta strandⁱ	677 – 679	Combined sources	3
Helixⁱ	680 – 694	Combined sources	15
Turnⁱ	700 – 703	Combined sources	4
Helixⁱ	706 – 722	Combined sources	17
Helixⁱ	725 – 740	Combined sources	16
Beta strandⁱ	746 – 748	Combined sources	3
Helixⁱ	749 – 764	Combined sources	16
Helixⁱ	766 – 769	Combined sources	4
Helixⁱ	772 – 796	Combined sources	25
Helixⁱ	803 – 805	Combined sources	3
Helixⁱ	807 – 812	Combined sources	6
Helixⁱ	813 – 823	Combined sources	11
Helixⁱ	825 – 835	Combined sources	11
Helixⁱ	837 – 839	Combined sources	3
Helixⁱ	840 – 857	Combined sources	18

Show more details

3D structure databases

ProteinModelPortalⁱ	O76074
SMRⁱ	O76074
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	O76074

EvolutionaryTraceⁱ

O76074

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	164 – 314	GAF 1Add BLAST	151
Domainⁱ	346 – 503	GAF 2Add BLAST	158
Domainⁱ	536 – 860	PDEasePROSITE-ProRule annotationAdd BLAST	325

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	10 – 24	Poly-GlnAdd BLAST		15

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.

Sequence similaritiesⁱ

Belongs to the cyclic nucleotide phosphodiesterase family.Curated

Keywords - Domainⁱ

Repeat

Phylogenomic databases

eggNOGⁱ	KOG3689 Eukaryota ENOG410XRI7 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119066
HOVERGENⁱ	HBG101207
KEGG Orthology (KO) More...KOⁱ	K13762
OMAⁱ	VQRCTIF
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G04JU
PhylomeDBⁱ	O76074
TreeFamⁱ	TF316499

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00077 HDc, 1 hit
Gene3Dⁱ	1.10.1300.10, 1 hit 3.30.450.40, 2 hits
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
PRINTSⁱ	PR00387 PDIESTERASE1
SMARTⁱ	View protein in SMART SM00065 GAF, 2 hits SM00471 HDc, 1 hit
PROSITEⁱ	View protein in PROSITE PS00126 PDEASE_I_1, 1 hit PS51845 PDEASE_I_2, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show all Align All

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

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
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

Checksum:ⁱ9E30C6C182F13388

Isoform PDE5A2 (identifier: O76074-2) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MLPFGDKTRE MVNAWFAERV HTIPVCKEGI RGHTESCSCP LQQSPRADNS 
        60         70         80         90        100
APGTPTRKIS ASEFDRPLRP IVVKDSEGTV SFLSDSEKKE QMPLTPPRFD 
       110        120        130        140        150
HDEGDQCSRL LELVKDISSH LDVTALCHKI FLHIHGLISA DRYSLFLVCE 
       160        170        180        190        200
DSSNDKFLIS RLFDVAEGST LEEVSNNCIR LEWNKGIVGH VAALGEPLNI 
       210        220        230        240        250
KDAYEDPRFN AEVDQITGYK TQSILCMPIK NHREEVVGVA QAINKKSGNG 
       260        270        280        290        300
GTFTEKDEKD FAAYLAFCGI VLHNAQLYET SLLENKRNQV LLDLASLIFE 
       310        320        330        340        350
EQQSLEVILK KIAATIISFM QVQKCTIFIV DEDCSDSFSS VFHMECEELE 
       360        370        380        390        400
KSSDTLTREH DANKINYMYA QYVKNTMEPL NIPDVSKDKR FPWTTENTGN 
       410        420        430        440        450
VNQQCIRSLL CTPIKNGKKN KVIGVCQLVN KMEENTGKVK PFNRNDEQFL 
       460        470        480        490        500
EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT LEVLSYHASA AEEETRELQS 
       510        520        530        540        550
LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL NLVQNFQMKH 
       560        570        580        590        600
EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE 
       610        620        630        640        650
ILALLIAALS HDLDHRGVNN SYIQRSEHPL AQLYCHSIME HHHFDQCLMI 
       660        670        680        690        700
LNSPGNQILS GLSIEEYKTT LKIIKQAILA TDLALYIKRR GEFFELIRKN 
       710        720        730        740        750
QFNLEDPHQK ELFLAMLMTA CDLSAITKPW PIQQRIAELV ATEFFDQGDR 
       760        770        780        790        800
ERKELNIEPT DLMNREKKNK IPSMQVGFID AICLQLYEAL THVSEDCFPL 
       810        820        830 
LDGCRKNRQK WQALAEQQEK MLINGESGQA KRN

Show »

Length:833

Mass (Da):94,805

Checksum:ⁱ41D0B4B1BAB57D6D

Computationally mapped potential isoform sequencesⁱ

There are 3 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

G5E9C5	G5E9C5_HUMAN	Phosphodiesterase Phosphodiesterase, EC 3.1.4.-	PDE5A hCG_38154	823	Annotation score:
H0YA14	H0YA14_HUMAN	cGMP-specific 3',5'-cyclic phosphod... cGMP-specific 3',5'-cyclic phosphodiesterase	PDE5A	185	Annotation score:
C9JGT3	C9JGT3_HUMAN	cGMP-specific 3',5'-cyclic phosphod... cGMP-specific 3',5'-cyclic phosphodiesterase	PDE5A	224	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	159	I → V in AAP31235 (PubMed:10393044).Curated	1
Sequence conflictⁱ	310	C → G in AAP31235 (PubMed:10393044).Curated	1
Sequence conflictⁱ	381	S → F in AAP31235 (PubMed:10393044).Curated	1
Sequence conflictⁱ	406	K → R in AAP31235 (PubMed:10393044).Curated	1
Sequence conflictⁱ	642	E → G in BAA81667 (Ref. 4) Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_027775	93	A → V5 PublicationsCorresponds to variant dbSNP:rs3733526Ensembl.		1
Natural variantⁱVAR_027776	181	S → A. Corresponds to variant dbSNP:rs17051276Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_004591	1 – 49	MERAG…FVRKA → MLPFGDK in isoform PDE5A2. 3 PublicationsAdd BLAST		49

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS34055.1 [O76074-2] CCDS3713.1 [O76074-1]
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
UniGeneⁱ	Hs.647971

Genome annotation databases

Ensemblⁱ	ENST00000264805; ENSP00000264805; ENSG00000138735 [O76074-2] ENST00000354960; ENSP00000347046; ENSG00000138735 [O76074-1]
GeneIDⁱ	8654
KEGGⁱ	hsa:8654
UCSC genome browser More...UCSCⁱ	uc003idf.4 human [O76074-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Protein	Similar proteins		Species	Score	Length	Source
O76074	Phosphodiesterase		HUMAN		823	UniRef100_O76074
cGMP-specific 3',5'-cyclic phosphodiesterase (Fragment)		HUMAN		224

Protein	Similar proteins		Species	Score	Length	Source
O76074	cGMP-specific 3',5'-cyclic phosphodiesterase	)	BOVIN		865	UniRef90_O76074
cGMP-specific 3',5'-cyclic phosphodiesterase		CANLF		865
cGMP-specific 3',5'-cyclic phosphodiesterase	)	MOUSE		865
cGMP-specific 3',5'-cyclic phosphodiesterase		RAT		833
Phosphodiesterase		HUMAN		823
+285

Protein	Similar proteins		Species	Score	Length	Source
O76074	cGMP-specific 3',5'-cyclic phosphodiesterase	)	BOVIN		865	UniRef50_O76074
cGMP-specific 3',5'-cyclic phosphodiesterase	)	MOUSE		865
cGMP-specific 3',5'-cyclic phosphodiesterase		CANLF		865
cGMP-specific 3',5'-cyclic phosphodiesterase		RAT		833
Phosphodiesterase		HUMAN		823
+473

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
CCDSⁱ	CCDS34055.1 [O76074-2] CCDS3713.1 [O76074-1]
PIRⁱ	JW0106
RefSeqⁱ	NP_001074.2, NM_001083.3 [O76074-1] NP_236914.2, NM_033430.2 [O76074-2] NP_246273.2, NM_033437.3
UniGeneⁱ	Hs.647971

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 entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1RKP	X-ray	2.05	A	535-860	[»]
	1T9R	X-ray	2.10	A	531-875	[»]
	1T9S	X-ray	2.00	A/B	534-858	[»]
	1TBF	X-ray	1.30	A	534-858	[»]
	1UDT	X-ray	2.30	A	537-860	[»]
	1UDU	X-ray	2.83	A/B	537-860	[»]
	1UHO	X-ray	2.50	A	537-860	[»]
	1XOZ	X-ray	1.37	A	534-875	[»]
	1XP0	X-ray	1.79	A	534-875	[»]
	2CHM	X-ray	1.60	A	534-656	[»]
				A	682-858	[»]
	2H40	X-ray	1.85	A	535-860	[»]
	2H42	X-ray	2.30	A/B/C	535-860	[»]
	2H44	X-ray	1.80	A	535-860	[»]
	2XSS	X-ray	2.50	A/B	346-509	[»]
	3B2R	X-ray	2.07	A/B	535-860	[»]
	3BJC	X-ray	2.00	A	1-875	[»]
	3HC8	X-ray	1.79	A	536-657	[»]
				A	682-858	[»]
	3HDZ	X-ray	1.80	A	536-657	[»]
				A	682-858	[»]
	3JWQ	X-ray	2.87	A/B/C/D	535-786	[»]
				A/B/C/D	827-860	[»]
	3JWR	X-ray	2.99	A/B	535-786	[»]
				A/B	827-860	[»]
	3LFV	X-ray	2.80	A/B	98-518	[»]
	3MF0	X-ray	3.10	A/B	89-518	[»]
	3SHY	X-ray	2.65	A	535-860	[»]
	3SHZ	X-ray	2.45	A	535-860	[»]
	3SIE	X-ray	1.93	A/B	535-860	[»]
	3TGE	X-ray	1.96	A	534-656	[»]
				A	682-858	[»]
	3TGG	X-ray	1.91	A	534-660	[»]
				A	662-858	[»]
	4G2W	X-ray	2.28	A	535-860	[»]
	4G2Y	X-ray	2.40	A	535-860	[»]
	4I9Z	X-ray	2.08	A	535-860	[»]
	4IA0	X-ray	2.17	A	535-860	[»]
	4MD6	X-ray	2.00	A	535-860	[»]
	4OEW	X-ray	2.44	A	535-860	[»]
	4OEX	X-ray	2.14	A	535-860	[»]
	5JO3	X-ray	1.49	B	534-858	[»]
	5ZZ2	X-ray	2.60	A	535-860	[»]
	6ACB	X-ray	2.80	A	535-860	[»]
ProteinModelPortalⁱ	O76074
SMRⁱ	O76074
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	114205, 8 interactors
DIPⁱ	DIP-46287N
IntActⁱ	O76074, 5 interactors
STRINGⁱ	9606.ENSP00000347046

Chemistry databases

BindingDBⁱ	O76074
ChEMBLⁱ	CHEMBL1827
DrugBankⁱ	DB07954 3-isobutyl-1-methyl-7H-xanthine DB06237 Avanafil DB00201 Caffeine DB04272 Citric Acid DB00975 Dipyridamole DB03597 Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine DB01972 Guanosine-5'-Monophosphate DB05415 OSI-461 DB00806 Pentoxifylline DB00203 Sildenafil DB00820 Tadalafil DB00277 Theophylline DB06267 Udenafil DB00862 Vardenafil
GuidetoPHARMACOLOGYⁱ	1304

PTM databases

iPTMnetⁱ	O76074
PhosphoSitePlusⁱ	O76074

Polymorphism and mutation databases

BioMutaⁱ	PDE5A

BioMutaⁱ

PDE5A

Proteomic databases

EPDⁱ	O76074
MaxQBⁱ	O76074
PaxDbⁱ	O76074
PeptideAtlasⁱ	O76074
PRIDEⁱ	O76074
ProteomicsDBⁱ	50374 50375 [O76074-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	8654
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000264805; ENSP00000264805; ENSG00000138735 [O76074-2] ENST00000354960; ENSP00000347046; ENSG00000138735 [O76074-1]
GeneIDⁱ	8654
KEGGⁱ	hsa:8654
UCSCⁱ	uc003idf.4 human [O76074-1]

Organism-specific databases

CTDⁱ	8654
DisGeNETⁱ	8654
EuPathDBⁱ	HostDB:ENSG00000138735.15
GeneCardsⁱ	PDE5A
HGNCⁱ	HGNC:8784 PDE5A
HPAⁱ	HPA004729 HPA012873
MIMⁱ	603310 gene
neXtProtⁱ	NX_O76074
OpenTargetsⁱ	ENSG00000138735
PharmGKBⁱ	PA33132
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3689 Eukaryota ENOG410XRI7 LUCA
GeneTreeⁱ	ENSGT00760000119066
HOVERGENⁱ	HBG101207
KOⁱ	K13762
OMAⁱ	VQRCTIF
OrthoDBⁱ	EOG091G04JU
PhylomeDBⁱ	O76074
TreeFamⁱ	TF316499

Enzyme and pathway databases

UniPathwayⁱ	UPA00763;UER00748
BRENDAⁱ	3.1.4.35 2681
Reactomeⁱ	R-HSA-418457 cGMP effects
SIGNORⁱ	O76074

Miscellaneous databases

ChiTaRSⁱ	PDE5A human
EvolutionaryTraceⁱ	O76074
GeneWikiⁱ	CGMP-specific_phosphodiesterase_type_5
GenomeRNAiⁱ	8654
Protein Ontology More...PROⁱ	PR:O76074
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000138735 Expressed in 189 organ(s), highest expression level in intestine
CleanExⁱ	HS_PDE5A
ExpressionAtlasⁱ	O76074 baseline and differential
Genevisibleⁱ	O76074 HS

Family and domain databases

CDDⁱ	cd00077 HDc, 1 hit
Gene3Dⁱ	1.10.1300.10, 1 hit 3.30.450.40, 2 hits
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
Pfamⁱ	View protein in Pfam PF01590 GAF, 2 hits PF00233 PDEase_I, 1 hit
PRINTSⁱ	PR00387 PDIESTERASE1
SMARTⁱ	View protein in SMART SM00065 GAF, 2 hits SM00471 HDc, 1 hit
PROSITEⁱ	View protein in PROSITE PS00126 PDEASE_I_1, 1 hit PS51845 PDEASE_I_2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PDE5A_HUMAN
Accessionⁱ	O76074Primary (citable) accession number: O76074 Secondary accession number(s): A0AV69 Q9Y6Z6
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
	Last sequence update:	January 11, 2011
	Last modified:	November 7, 2018
	This is version 181 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

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

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UniProtKB - O76074 (PDE5A_HUMAN)

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cGMP-specific 3',5'-cyclic phosphodiesterase

PDE5A

Select a section on the left to see content.

<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

Caution

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

Sites

<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

GO - Biological processi

Enzyme and pathway databases

<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

Organism-specific databases

<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

Cytosol

<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

Chemistry databases

Polymorphism and mutation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

Protein-protein interaction databases

Chemistry databases

<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

3D structure databases

Miscellaneous databases

<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

Compositional bias

<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

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<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 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

Documents

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Functionⁱ

Pathwayⁱ: 3',5'-cyclic GMP degradation

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ