Q9Y233 · PDE10_HUMAN
- ProteincAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
- GenePDE10A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1055 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10373451, PubMed:10393245, PubMed:16330539, PubMed:17389385, PubMed:27058447).
Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10373451, PubMed:10393245, PubMed:17389385, PubMed:27058447).
May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:27058447).
Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10373451, PubMed:10393245, PubMed:17389385, PubMed:27058447).
May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:27058447).
Catalytic activity
- a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H+
- 3',5'-cyclic AMP + H2O = AMP + H+
- 3',5'-cyclic GMP + H2O = GMP + H+
Cofactor
Note: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
Activity regulation
Inhibited by dipyridamole and moderately by IBMX. cGMP acts as an allosteric activator.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.26 μM | cAMP | |||||
7.2 μM | cGMP | |||||
56 nM | cAMP | |||||
4.4 μM | cGMP |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
507 nmol/min/mg | for cAMP | ||||
1860 nmol/min/mg | for cGMP |
Pathway
Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 562-563 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: RC | ||||||
Binding site | 606-607 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: IA | ||||||
Binding site | 640 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 659 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Active site | 791 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 791 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 791 | 3',5'-cyclic GMP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 795 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 829 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 830 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 830 | a divalent metal cation 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 940 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 992 | 3',5'-cyclic AMP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 992 | 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 | cAMP binding | |
Molecular Function | cGMP binding | |
Molecular Function | cGMP-stimulated cyclic-nucleotide phosphodiesterase activity | |
Molecular Function | metal ion binding | |
Biological Process | cAMP catabolic process | |
Biological Process | cAMP-mediated signaling | |
Biological Process | cGMP catabolic process | |
Biological Process | negative regulation of cGMP-mediated signaling |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namecAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
- EC number
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y233
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Dyskinesia, limb and orofacial, infantile-onset (IOLOD)
- Note
- DescriptionAn autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable.
- See alsoMIM:616921
Natural variants in IOLOD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076798 | 373 | Y>C | in IOLOD; decreased protein abundance; dbSNP:rs778899140 | |
VAR_076799 | 382 | A>P | in IOLOD; decreased protein abundance; dbSNP:rs875989839 |
Striatal degeneration, autosomal dominant 2 (ADSD2)
- Note
- DescriptionAn autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis.
- See alsoMIM:616922
Natural variants in ADSD2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076800 | 566 | F>L | in ADSD2; no effect on basal 3',5'-cyclic-nucleotide phosphodiesterase activity; the mutation severely disrupts the stimulatory effect on the enzyme activity mediated by cAMP binding; dbSNP:rs875989841 | |
VAR_076801 | 600 | F>L | in ADSD2; no effect on basal 3',5'-cyclic-nucleotide phosphodiesterase activity; the mutation severely disrupts the stimulatory effect on the enzyme activity mediated by cAMP binding; dbSNP:rs875989840 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_076798 | 373 | in IOLOD; decreased protein abundance; dbSNP:rs778899140 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_076799 | 382 | in IOLOD; decreased protein abundance; dbSNP:rs875989839 | |||
Sequence: A → P | ||||||
Natural variant | VAR_076800 | 566 | in ADSD2; no effect on basal 3',5'-cyclic-nucleotide phosphodiesterase activity; the mutation severely disrupts the stimulatory effect on the enzyme activity mediated by cAMP binding; dbSNP:rs875989841 | |||
Sequence: F → L | ||||||
Natural variant | VAR_008797 | 579 | ||||
Sequence: L → P | ||||||
Natural variant | VAR_076801 | 600 | in ADSD2; no effect on basal 3',5'-cyclic-nucleotide phosphodiesterase activity; the mutation severely disrupts the stimulatory effect on the enzyme activity mediated by cAMP binding; dbSNP:rs875989840 | |||
Sequence: F → L | ||||||
Mutagenesis | 830 | Loss of activity and of zinc binding. | ||||
Sequence: D → A | ||||||
Mutagenesis | 830 | Reduces activity 1000-fold. | ||||
Sequence: D → N | ||||||
Natural variant | VAR_047822 | 982 | in dbSNP:rs2224252 | |||
Sequence: R → K | ||||||
Natural variant | VAR_047823 | 983 | in dbSNP:rs2860112 | |||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 879 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000198843 | 1-1055 | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | |||
Sequence: MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAERAAPPRPPLSSAGRPSPAGGPGALSARGGGCGWVAARAPLALAFSSRVPSSSPSFFYFWPPPPPPPPSFLPSSSAFHLPVRLPGREGAAAAAAAGGGGDAGGGGGGGQEAAPLSVPTSSSHRGGGGSGGGRRRLFLSPALQGLLLPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGGGGQTPRRPQGASFALAAAAALLFGSDMEDGPSNNASCFRRLTECFLSPSLTDEKVKAYLSLHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAPKEVSRYQDTNMQGVVYELNSYIEQRLDTGGDNQLLLYELSSIIKIATKADGFALYFLGECNNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLESGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVCRGLAKQTELNDFLLDVSKTYFDNIVAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELYSDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYTGYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALALHCANMYHRIRHSECIYRVTMEKLSYHSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNIFSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGEETATWISSPSVAQKAAASED | ||||||
Modified residue | 282 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Isoform PDE10A2
Phosphorylated on Thr-16.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-90 | Disordered | ||||
Sequence: MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAERAAPPRPPLSSAGRPSPAGGPGALSARGGG | ||||||
Region | 151-193 | Disordered | ||||
Sequence: AAAAGGGGDAGGGGGGGQEAAPLSVPTSSSHRGGGGSGGGRRR | ||||||
Region | 205-250 | Disordered | ||||
Sequence: LPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGGGGQTPRRPQG | ||||||
Domain | 367-510 | GAF 1 | ||||
Sequence: DNQLLLYELSSIIKIATKADGFALYFLGECNNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLESGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAI | ||||||
Domain | 542-688 | GAF 2 | ||||
Sequence: AIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELYSDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYTGYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALAL | ||||||
Domain | 718-1035 | PDEase | ||||
Sequence: TSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNIFSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGE |
Domain
The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.
Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.
Sequence similarities
Belongs to the cyclic nucleotide phosphodiesterase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing & Alternative initiation.
Q9Y233-3
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.
- Name3
- NoteProduced by alternative initiation. Based on proteomic data.
- Length1,055
- Mass (Da)114,946
- Last updated2024-01-24 v2
- Checksum9FD62FD5851B001A
Q9Y233-1
- NamePDE10A1
- Differences from canonical
- 1-289: MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAERAAPPRPPLSSAGRPSPAGGPGALSARGGGCGWVAARAPLALAFSSRVPSSSPSFFYFWPPPPPPPPSFLPSSSAFHLPVRLPGREGAAAAAAAGGGGDAGGGGGGGQEAAPLSVPTSSSHRGGGGSGGGRRRLFLSPALQGLLLPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGGGGQTPRRPQGASFALAAAAALLFGSDMEDGPSNNASCFRRLTECFLSPS → MRIEERKSQHLTG
Q9Y233-2
- NamePDE10A2
- Differences from canonical
- 1-266: Missing
Computationally mapped potential isoform sequences
There are 15 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1B1UZQ1 | A0A1B1UZQ1_HUMAN | PDE10A | 709 | ||
A0AAA9X175 | A0AAA9X175_HUMAN | PDE10A | 505 | ||
A0A5F9ZI67 | A0A5F9ZI67_HUMAN | PDE10A | 806 | ||
A0A5F9ZHF9 | A0A5F9ZHF9_HUMAN | PDE10A | 820 | ||
A0A3B3IRU7 | A0A3B3IRU7_HUMAN | PDE10A | 772 | ||
A0A3B3IS50 | A0A3B3IS50_HUMAN | PDE10A | 52 | ||
A0A3B3ISJ6 | A0A3B3ISJ6_HUMAN | PDE10A | 791 | ||
A0A3B3IT18 | A0A3B3IT18_HUMAN | PDE10A | 93 | ||
A0A3B3ITT8 | A0A3B3ITT8_HUMAN | PDE10A | 847 | ||
A0A3B3IRL3 | A0A3B3IRL3_HUMAN | PDE10A | 60 | ||
A0A7I2YQI4 | A0A7I2YQI4_HUMAN | PDE10A | 93 | ||
A0A7I2YQV2 | A0A7I2YQV2_HUMAN | PDE10A | 802 | ||
A0A087WUD0 | A0A087WUD0_HUMAN | PDE10A | 183 | ||
A0A7I2V301 | A0A7I2V301_HUMAN | PDE10A | 308 | ||
A0A7I2V618 | A0A7I2V618_HUMAN | PDE10A | 349 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_062216 | 1-266 | in isoform PDE10A2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_062215 | 1-289 | in isoform PDE10A1 | |||
Sequence: MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAERAAPPRPPLSSAGRPSPAGGPGALSARGGGCGWVAARAPLALAFSSRVPSSSPSFFYFWPPPPPPPPSFLPSSSAFHLPVRLPGREGAAAAAAAGGGGDAGGGGGGGQEAAPLSVPTSSSHRGGGGSGGGRRRLFLSPALQGLLLPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGGGGQTPRRPQGASFALAAAAALLFGSDMEDGPSNNASCFRRLTECFLSPS → MRIEERKSQHLTG | ||||||
Sequence conflict | 933 | in Ref. 4; CAG38804 | ||||
Sequence: G → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB026816 EMBL· GenBank· DDBJ | BAA84467.1 EMBL· GenBank· DDBJ | mRNA | ||
AB020593 EMBL· GenBank· DDBJ | BAA78034.1 EMBL· GenBank· DDBJ | mRNA | ||
AF127479 EMBL· GenBank· DDBJ | AAD32595.1 EMBL· GenBank· DDBJ | mRNA | ||
AF127480 EMBL· GenBank· DDBJ | AAD32596.1 EMBL· GenBank· DDBJ | mRNA | ||
CR536567 EMBL· GenBank· DDBJ | CAG38804.1 EMBL· GenBank· DDBJ | mRNA | ||
AL117345 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL136130 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL160160 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL121789 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL590302 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL591962 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KF458352 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KF458359 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC104858 EMBL· GenBank· DDBJ | AAI04859.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104860 EMBL· GenBank· DDBJ | AAI04861.1 EMBL· GenBank· DDBJ | mRNA | ||
AB041798 EMBL· GenBank· DDBJ | BAB16383.1 EMBL· GenBank· DDBJ | Genomic DNA |