O76074 · PDE5A_HUMAN
- ProteincGMP-specific 3',5'-cyclic phosphodiesterase
- GenePDE5A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids875 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
Catalytic activity
- 3',5'-cyclic GMP + H2O = GMP + H+This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Pathway
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 613 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 617 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 653 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 654 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 654 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 764 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 817 | 3',5'-cyclic GMP (UniProtKB | ChEBI) | ||||
Sequence: Q |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | 3',5'-cyclic-AMP phosphodiesterase activity | |
Molecular Function | 3',5'-cyclic-GMP phosphodiesterase activity | |
Molecular Function | 3',5'-cyclic-nucleotide phosphodiesterase activity | |
Molecular Function | cGMP binding | |
Molecular Function | metal ion binding | |
Biological Process | cAMP-mediated signaling | |
Biological Process | cGMP catabolic process | |
Biological Process | negative regulation of cardiac muscle contraction | |
Biological Process | negative regulation of T cell proliferation | |
Biological Process | oocyte development | |
Biological Process | positive regulation of cardiac muscle hypertrophy | |
Biological Process | positive regulation of oocyte development | |
Biological Process | regulation of nitric oxide mediated signal transduction | |
Biological Process | relaxation of cardiac muscle | |
Biological Process | T cell proliferation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namecGMP-specific 3',5'-cyclic phosphodiesterase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO76074
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_027775 | 93 | in dbSNP:rs3733526 | |||
Sequence: A → V | ||||||
Natural variant | VAR_027776 | 181 | in dbSNP:rs17051276 | |||
Sequence: S → A | ||||||
Mutagenesis | 767 | Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with Y-775 and Y-853. | ||||
Sequence: A → N | ||||||
Mutagenesis | 775 | Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with N-767 and Y-853. | ||||
Sequence: Q → Y | ||||||
Mutagenesis | 853 | Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with N-767 and Y-775. | ||||
Sequence: W → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 845 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000198823 | 1-875 | UniProt | cGMP-specific 3',5'-cyclic phosphodiesterase | |||
Sequence: MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 102 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 102 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 104 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 137 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylation by PRKG1 leads to its activation
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O76074 | PRKG1 Q13976 | 4 | EBI-9023531, EBI-3952014 | |
BINARY | O76074 | SPG21 Q9NZD8 | 3 | EBI-9023531, EBI-742688 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-29 | Disordered | ||||
Sequence: MERAGPSFGQQRQQQQPQQQKQQQRDQDS | ||||||
Compositional bias | 7-27 | Polar residues | ||||
Sequence: SFGQQRQQQQPQQQKQQQRDQ | ||||||
Compositional bias | 78-99 | Polar residues | ||||
Sequence: SCSCPLQQSPRADNSAPGTPTR | ||||||
Region | 78-102 | Disordered | ||||
Sequence: SCSCPLQQSPRADNSAPGTPTRKIS | ||||||
Domain | 164-314 | GAF 1 | ||||
Sequence: DVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVL | ||||||
Domain | 346-503 | GAF 2 | ||||
Sequence: SLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGI | ||||||
Domain | 536-860 | PDEase | ||||
Sequence: ETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQ |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O76074-1
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.
- NamePDE5A1
- Length875
- Mass (Da)99,985
- Last updated2011-01-11 v2
- Checksum9E30C6C182F13388
O76074-2
- NamePDE5A2
- Differences from canonical
- 1-49: MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKA → MLPFGDK
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_004591 | 1-49 | in isoform PDE5A2 | |||
Sequence: MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKA → MLPFGDK | ||||||
Compositional bias | 7-27 | Polar residues | ||||
Sequence: SFGQQRQQQQPQQQKQQQRDQ | ||||||
Compositional bias | 78-99 | Polar residues | ||||
Sequence: SCSCPLQQSPRADNSAPGTPTR | ||||||
Sequence conflict | 159 | in Ref. 9; AAP31235 | ||||
Sequence: I → V | ||||||
Sequence conflict | 310 | in Ref. 9; AAP31235 | ||||
Sequence: C → G | ||||||
Sequence conflict | 381 | in Ref. 9; AAP31235 | ||||
Sequence: S → F | ||||||
Sequence conflict | 406 | in Ref. 9; AAP31235 | ||||
Sequence: K → R | ||||||
Sequence conflict | 642 | in Ref. 4; BAA81667 | ||||
Sequence: E → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF043731 EMBL· GenBank· DDBJ | AAC63967.1 EMBL· GenBank· DDBJ | mRNA | ||
AF043732 EMBL· GenBank· DDBJ | AAC63968.1 EMBL· GenBank· DDBJ | mRNA | ||
AB001635 EMBL· GenBank· DDBJ | BAA33372.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
D89094 EMBL· GenBank· DDBJ | BAA28945.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ004865 EMBL· GenBank· DDBJ | CAA06170.1 EMBL· GenBank· DDBJ | mRNA | ||
AB015656 EMBL· GenBank· DDBJ | BAA81667.1 EMBL· GenBank· DDBJ | mRNA | ||
AY264918 EMBL· GenBank· DDBJ | AAP21809.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290189 EMBL· GenBank· DDBJ | BAF82878.1 EMBL· GenBank· DDBJ | mRNA | ||
AC093752 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC080089 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC126233 EMBL· GenBank· DDBJ | AAI26234.1 EMBL· GenBank· DDBJ | mRNA | ||
AY266363 EMBL· GenBank· DDBJ | AAP31235.1 EMBL· GenBank· DDBJ | mRNA |