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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-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

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Enzyme 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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei613 – 6131Proton donorBy similarity
Metal bindingi617 – 6171Zinc; via tele nitrogen1 Publication
Metal bindingi653 – 6531Zinc; via tele nitrogen1 Publication
Metal bindingi654 – 6541Magnesium1 Publication
Metal bindingi654 – 6541Zinc1 Publication
Metal bindingi764 – 7641Zinc1 Publication
Binding sitei817 – 8171cGMP1 Publication

GO - Molecular functioni

  • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC
  • 3',5'-cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
  • cGMP binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.1.4.35. 2681.
ReactomeiREACT_23767. cGMP effects.
UniPathwayiUPA00763; 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:8784. PDE5A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33132.

Chemistry

DrugBankiDB06237. Avanafil.
DB00201. Caffeine.
DB00975. Dipyridamole.
DB00806. Pentoxifylline.
DB00203. Sildenafil.
DB00820. Tadalafil.
DB00277. Theophylline.
DB06267. Udenafil.
DB00862. Vardenafil.

Polymorphism and mutation databases

BioMutaiPDE5A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 875875cGMP-specific 3',5'-cyclic phosphodiesterasePRO_0000198823Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021PhosphoserineSequence Analysis

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

MaxQBiO76074.
PaxDbiO76074.
PRIDEiO76074.

PTM databases

PhosphoSiteiO76074.

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

BgeeiO76074.
CleanExiHS_PDE5A.
ExpressionAtlasiO76074. baseline and differential.
GenevestigatoriO76074.

Organism-specific databases

HPAiHPA004729.
HPA012873.

Interactioni

Protein-protein interaction databases

BioGridi114205. 1 interaction.
DIPiDIP-46287N.
STRINGi9606.ENSP00000347046.

Structurei

Secondary structure

1
875
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi103 – 1064Combined sources
Beta strandi115 – 1173Combined sources
Turni118 – 1203Combined sources
Beta strandi121 – 1244Combined sources
Helixi148 – 16013Combined sources
Helixi165 – 17713Combined sources
Beta strandi182 – 19211Combined sources
Beta strandi198 – 2058Combined sources
Beta strandi208 – 2103Combined sources
Beta strandi213 – 2186Combined sources
Beta strandi221 – 2244Combined sources
Helixi228 – 2369Combined sources
Beta strandi240 – 2434Combined sources
Helixi245 – 2473Combined sources
Helixi254 – 2596Combined sources
Beta strandi266 – 2727Combined sources
Beta strandi278 – 28710Combined sources
Helixi299 – 34042Combined sources
Turni342 – 3454Combined sources
Helixi346 – 36217Combined sources
Beta strandi365 – 3728Combined sources
Beta strandi374 – 3763Combined sources
Beta strandi379 – 3879Combined sources
Turni388 – 3903Combined sources
Beta strandi391 – 3933Combined sources
Helixi400 – 4034Combined sources
Helixi407 – 4093Combined sources
Helixi410 – 4189Combined sources
Beta strandi422 – 4254Combined sources
Turni427 – 4293Combined sources
Beta strandi431 – 4333Combined sources
Beta strandi451 – 4577Combined sources
Beta strandi461 – 47111Combined sources
Turni476 – 4783Combined sources
Helixi486 – 50621Combined sources
Helixi535 – 54511Combined sources
Helixi551 – 5544Combined sources
Turni555 – 5573Combined sources
Helixi568 – 58114Combined sources
Helixi584 – 5874Combined sources
Helixi592 – 60413Combined sources
Turni606 – 6083Combined sources
Beta strandi610 – 6145Combined sources
Helixi615 – 63016Combined sources
Turni631 – 6333Combined sources
Helixi635 – 6373Combined sources
Helixi640 – 65213Combined sources
Turni653 – 6564Combined sources
Helixi662 – 6676Combined sources
Helixi671 – 6755Combined sources
Beta strandi677 – 6793Combined sources
Helixi680 – 69415Combined sources
Turni700 – 7034Combined sources
Helixi706 – 72217Combined sources
Helixi725 – 74016Combined sources
Beta strandi746 – 7483Combined sources
Helixi749 – 76416Combined sources
Helixi766 – 7694Combined sources
Helixi772 – 79625Combined sources
Helixi803 – 8053Combined sources
Helixi807 – 8126Combined sources
Helixi813 – 82311Combined sources
Helixi825 – 83511Combined sources
Helixi837 – 8393Combined sources
Helixi840 – 85718Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliO76074.
SMRiO76074. Positions 98-860.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76074.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini164 – 314151GAF 1Add
BLAST
Domaini346 – 503158GAF 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni588 – 853266CatalyticBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi10 – 2415Poly-GlnAdd
BLAST

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

Contains 2 GAF domains.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG270709.
GeneTreeiENSGT00760000119066.
HOVERGENiHBG101207.
KOiK13762.
OMAiREHDANK.
OrthoDBiEOG7RRF69.
PhylomeDBiO76074.
TreeFamiTF316499.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom_like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti159 – 1591I → V in AAP31235 (PubMed:10393044).Curated
Sequence conflicti310 – 3101C → G in AAP31235 (PubMed:10393044).Curated
Sequence conflicti381 – 3811S → F in AAP31235 (PubMed:10393044).Curated
Sequence conflicti406 – 4061K → R in AAP31235 (PubMed:10393044).Curated
Sequence conflicti642 – 6421E → G in BAA81667 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931A → V.5 Publications
Corresponds to variant rs3733526 [ dbSNP | Ensembl ].
VAR_027775
Natural varianti181 – 1811S → A.
Corresponds to variant rs17051276 [ dbSNP | Ensembl ].
VAR_027776

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4949MERAG…FVRKA → MLPFGDK in isoform PDE5A2. 3 PublicationsVSP_004591Add
BLAST

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.
UniGeneiHs.647971.

Genome annotation databases

EnsembliENST00000264805; ENSP00000264805; ENSG00000138735. [O76074-2]
ENST00000354960; ENSP00000347046; ENSG00000138735. [O76074-1]
GeneIDi8654.
KEGGihsa:8654.
UCSCiuc003idf.3. human. [O76074-2]
uc003idg.3. human. [O76074-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
UniGeneiHs.647971.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliO76074.
SMRiO76074. Positions 98-860.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114205. 1 interaction.
DIPiDIP-46287N.
STRINGi9606.ENSP00000347046.

Chemistry

BindingDBiO76074.
ChEMBLiCHEMBL2111400.
DrugBankiDB06237. Avanafil.
DB00201. Caffeine.
DB00975. Dipyridamole.
DB00806. Pentoxifylline.
DB00203. Sildenafil.
DB00820. Tadalafil.
DB00277. Theophylline.
DB06267. Udenafil.
DB00862. Vardenafil.
GuidetoPHARMACOLOGYi1304.

PTM databases

PhosphoSiteiO76074.

Polymorphism and mutation databases

BioMutaiPDE5A.

Proteomic databases

MaxQBiO76074.
PaxDbiO76074.
PRIDEiO76074.

Protocols and materials databases

DNASUi8654.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264805; ENSP00000264805; ENSG00000138735. [O76074-2]
ENST00000354960; ENSP00000347046; ENSG00000138735. [O76074-1]
GeneIDi8654.
KEGGihsa:8654.
UCSCiuc003idf.3. human. [O76074-2]
uc003idg.3. human. [O76074-1]

Organism-specific databases

CTDi8654.
GeneCardsiGC04M120415.
HGNCiHGNC:8784. PDE5A.
HPAiHPA004729.
HPA012873.
MIMi603310. gene.
neXtProtiNX_O76074.
PharmGKBiPA33132.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG270709.
GeneTreeiENSGT00760000119066.
HOVERGENiHBG101207.
KOiK13762.
OMAiREHDANK.
OrthoDBiEOG7RRF69.
PhylomeDBiO76074.
TreeFamiTF316499.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
BRENDAi3.1.4.35. 2681.
ReactomeiREACT_23767. cGMP effects.

Miscellaneous databases

ChiTaRSiPDE5A. human.
EvolutionaryTraceiO76074.
GeneWikiiCGMP-specific_phosphodiesterase_type_5.
GenomeRNAii8654.
NextBioi32453.
PROiO76074.
SOURCEiSearch...

Gene expression databases

BgeeiO76074.
CleanExiHS_PDE5A.
ExpressionAtlasiO76074. baseline and differential.
GenevestigatoriO76074.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom_like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase."
    Loughney K., Hill T.R., Florio V.A., Uher L., Rosman G.J., Wolda S.L., Jones B.A., Howard M.L., McAllister-Lucas L.M., Sonnenburg W.K., Francis S.H., Corbin J.D., Beavo J.A., Ferguson K.
    Gene 216:139-147(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE5A1 AND PDE5A2), FUNCTION, CATALYTIC ACTIVITY, VARIANT VAL-93.
  2. "Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene."
    Yanaka N., Kotera J., Ohtsuka A., Akatsuka H., Imai Y., Michibata H., Fujishige K., Kawai E., Takebayashi S., Okumura K., Omori K.
    Eur. J. Biochem. 255:391-399(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM PDE5A1), VARIANT VAL-93.
    Tissue: Lung and Placenta.
  3. "Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase."
    Stacey P., Rulten S., Dapling A., Phillips S.C.
    Biochem. Biophys. Res. Commun. 247:249-254(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A1), VARIANT VAL-93.
    Tissue: Prostate and Skeletal muscle.
  4. "Molecular cloning and characterization of human cGMP-specific phosphodiesterase 5A2 cDNA."
    Kotera J., Imai Y., Omori K.
    Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A2), VARIANT VAL-93.
    Tissue: Lung.
  5. "PDE5A splice variants in T84 cells."
    Sopory S., Visweswariah S.S.
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A2).
    Tissue: Colon carcinoma.
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE5A1), VARIANT VAL-93.
    Tissue: Thalamus.
  7. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE5A1).
  9. "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells."
    Zhou L., Thompson W.J., Potter D.E.
    Invest. Ophthalmol. Vis. Sci. 40:1745-1752(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 157-411.
    Tissue: Trabecular meshwork.
  10. "Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells."
    Rybalkin S.D., Rybalkina I.G., Feil R., Hofmann F., Beavo J.A.
    J. Biol. Chem. 277:3310-3317(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY PRKG1.
  11. "Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules."
    Sung B.-J., Hwang K.Y., Jeon Y.H., Lee J.I., Heo Y.-S., Kim J.H., Moon J., Yoon J.M., Hyun Y.-L., Kim E., Eum S.J., Park S.-Y., Lee J.-O., Lee T.G., Ro S., Cho J.M.
    Nature 425:98-102(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 537-860 IN COMPLEX WITH ZINC; MAGNESIUM AND THE INHIBITORS SILDENAFIL; TADALAFIL AND VARDENAFIL, COFACTOR, ENZYME REGULATION.
  12. Cited for: FUNCTION.

Entry informationi

Entry nameiPDE5A_HUMAN
AccessioniPrimary (citable) accession number: O76074
Secondary accession number(s): A0AV69
, A8K2C4, O75026, O75887, Q86UI0, Q86V66, Q9Y6Z6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 11, 2011
Last modified: May 27, 2015
This is version 151 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

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

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.