PDE10A

Protein identityUniProt · HPA

UniProt accession

Q9Y233

Gene

PDE10A

Ensembl

ENSG00000112541

Chromosome

6

Canonical length

1055 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

1055 residues, UniProt reviewed canonical sequence.

>Q9Y233|PDE10A
     1  MASLEEPLAP RPQGPLPAAG DEPGCGPGKL RPEPRLSAAG GGSAAGPGPA PEWPGRGRAE
    61  RAAPPRPPLS SAGRPSPAGG PGALSARGGG CGWVAARAPL ALAFSSRVPS SSPSFFYFWP
   121  PPPPPPPSFL PSSSAFHLPV RLPGREGAAA AAAAGGGGDA GGGGGGGQEA APLSVPTSSS
   181  HRGGGGSGGG RRRLFLSPAL QGLLLPARAG PRPPPPPRLP LGQAARRAGS PGFPGAGPGG
   241  GGQTPRRPQG ASFALAAAAA LLFGSDMEDG PSNNASCFRR LTECFLSPSL TDEKVKAYLS
   301  LHPQVLDEFV SESVSAETVE KWLKRKNNKS EDESAPKEVS RYQDTNMQGV VYELNSYIEQ
   361  RLDTGGDNQL LLYELSSIIK IATKADGFAL YFLGECNNSL CIFTPPGIKE GKPRLIPAGP
   421  ITQGTTVSAY VAKSRKTLLV EDILGDERFP RGTGLESGTR IQSVLCLPIV TAIGDLIGIL
   481  ELYRHWGKEA FCLSHQEVAT ANLAWASVAI HQVQVCRGLA KQTELNDFLL DVSKTYFDNI
   541  VAIDSLLEHI MIYAKNLVNA DRCALFQVDH KNKELYSDLF DIGEEKEGKP VFKKTKEIRF
   601  SIEKGIAGQV ARTGEVLNIP DAYADPRFNR EVDLYTGYTT RNILCMPIVS RGSVIGVVQM
   661  VNKISGSAFS KTDENNFKMF AVFCALALHC ANMYHRIRHS ECIYRVTMEK LSYHSICTSE
   721  EWQGLMQFTL PVRLCKEIEL FHFDIGPFEN MWPGIFVYMV HRSCGTSCFE LEKLCRFIMS
   781  VKKNYRRVPY HNWKHAVTVA HCMYAILQNN HTLFTDLERK GLLIACLCHD LDHRGFSNSY
   841  LQKFDHPLAA LYSTSTMEQH HFSQTVSILQ LEGHNIFSTL SSSEYEQVLE IIRKAIIATD
   901  LALYFGNRKQ LEEMYQTGSL NLNNQSHRDR VIGLMMTACD LCSVTKLWPV TKLTANDIYA
   961  EFWAEGDEMK KLGIQPIPMM DRDKKDEVPQ GQLGFYNAVA IPCYTTLTQI LPPTEPLLKA
  1021  CRDNLSQWEK VIRGEETATW ISSPSVAQKA AASED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDE10A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

3.3 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDE10A.

Disease | AllUniProt

Conditions PDE10A is implicated in, by any mechanism.

• Dyskinesia, limb and orofacial, infantile-onset (IOLOD) MIM:616921
• Striatal degeneration, autosomal dominant 2 (ADSD2) MIM:616922

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 308 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Infantile-onset generalized dyskinesia with orofacial involvement
• Striatal degeneration, autosomal dominant 2
• Global developmental delay
• Generalized hypotonia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

3.76

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cAMP catabolic process
• cGMP catabolic process
• negative regulation of cAMP/PKA signal transduction
• negative regulation of cGMP-mediated signaling
• regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• signal transduction

Molecular functions

• 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity
• 3',5'-cyclic-AMP phosphodiesterase activity
• 3',5'-cyclic-GMP phosphodiesterase activity
• 3',5'-cyclic-nucleotide phosphodiesterase activity
• cAMP binding
• cGMP binding
• metal ion binding

Cellular components

• cytosol
• glutamatergic synapse

Protein domainsUniProt · Pfam · InterPro

• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain
• GAF domain
• HD/PDEase domain
• 3'5'-cyclic nucleotide phosphodiesterase
• 3'5'-cyclic nucleotide phosphodiesterase, conserved site
• GAF-like domain superfamily
• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily
• 3'5'-cyclic nucleotide phosphodiesterase
• GAF domain

KeywordsUniProt

• Allosteric enzyme
• Alternative initiation
• cAMP
• cAMP-binding
• cGMP
• cGMP-binding
• Cytoplasm
• Hydrolase
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Repeat