PDE8B

Protein identityUniProt · HPA

UniProt accession

O95263

Gene

PDE8B

Ensembl

ENSG00000113231

Chromosome

5

Canonical length

885 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

885 residues, UniProt reviewed canonical sequence.

>O95263|PDE8B
     1  MGCAPSIHVS QSGVIYCRDS DESSSPRQTT SVSQGPAAPL PGLFVQTDAA DAIPPSRASG
    61  PPSVARVRRA RTELGSGSSA GSAAPAATTS RGRRRHCCSS AEAETQTCYT SVKQVSSAEV
   121  RIGPMRLTQD PIQVLLIFAK EDSQSDGFWW ACDRAGYRCN IARTPESALE CFLDKHHEII
   181  VIDHRQTQNF DAEAVCRSIR ATNPSEHTVI LAVVSRVSDD HEEASVLPLL HAGFNRRFME
   241  NSSIIACYNE LIQIEHGEVR SQFKLRACNS VFTALDHCHE AIEITSDDHV IQYVNPAFER
   301  MMGYHKGELL GKELADLPKS DKNRADLLDT INTCIKKGKE WQGVYYARRK SGDSIQQHVK
   361  ITPVIGQGGK IRHFVSLKKL CCTTDNNKQI HKIHRDSGDN SQTEPHSFRY KNRRKESIDV
   421  KSISSRGSDA PSLQNRRYPS MARIHSMTIE APITKVINII NAAQENSPVT VAEALDRVLE
   481  ILRTTELYSP QLGTKDEDPH TSDLVGGLMT DGLRRLSGNE YVFTKNVHQS HSHLAMPITI
   541  NDVPPCISQL LDNEESWDFN IFELEAITHK RPLVYLGLKV FSRFGVCEFL NCSETTLRAW
   601  FQVIEANYHS SNAYHNSTHA ADVLHATAFF LGKERVKGSL DQLDEVAALI AATVHDVDHP
   661  GRTNSFLCNA GSELAVLYND TAVLESHHTA LAFQLTVKDT KCNIFKNIDR NHYRTLRQAI
   721  IDMVLATEMT KHFEHVNKFV NSINKPMAAE IEGSDCECNP AGKNFPENQI LIKRMMIKCA
   781  DVANPCRPLD LCIEWAGRIS EEYFAQTDEE KRQGLPVVMP VFDRNTCSIP KSQISFIDYF
   841  ITDMFDAWDA FAHLPALMQH LADNYKHWKT LDDLKCKSLR LPSDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDE8B 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)

0.35

Highest tissue expression

117 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDE8B.

Disease | AllUniProt

Conditions PDE8B is implicated in, by any mechanism.

• Striatal degeneration, autosomal dominant 1 (ADSD1) MIM:609161
• Primary pigmented nodular adrenocortical disease 3 (PPNAD3) MIM:614190

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 356 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant striatal neurodegeneration type 1
• Pigmented nodular adrenocortical disease, primary, 3
• Inborn genetic diseases
• PDE8B-Related Disorders

Disease | ImmuneIEDB

Conditions an epitope on PDE8B was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

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)

0.25

gnomAD pLI

1

gnomAD missense Z

3

DepMap mean gene effect

-0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• behavioral fear response
• cAMP catabolic process
• negative regulation of cAMP/PKA signal transduction
• negative regulation of insulin secretion involved in cellular response to glucose stimulus
• neuromuscular process controlling balance
• operant conditioning
• positive regulation of ERK1 and ERK2 cascade
• signal transduction
• visual learning
• negative regulation of steroid hormone biosynthetic process

Molecular functions

• 3',5'-cyclic-AMP phosphodiesterase activity
• 3',5'-cyclic-GMP phosphodiesterase activity
• metal ion binding

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• PAS domain
• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain
• HD/PDEase domain
• 3'5'-cyclic nucleotide phosphodiesterase
• 3'5'-cyclic nucleotide phosphodiesterase, conserved site
• PAS domain superfamily
• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily
• PDE8-like, REC N-terminal domain
• 3'5'-cyclic nucleotide phosphodiesterase
• PDE8 phosphodiesterase
• PAS domain
• PDE8A-like, N-terminal domain

KeywordsUniProt

• cAMP
• Cushing syndrome
• Hydrolase
• Metal-binding
• Phosphoprotein