PDE4D

Protein identityUniProt · HPA

UniProt accession

Q08499

Gene

PDE4D

Ensembl

ENSG00000113448

Chromosome

5

Canonical length

809 aa

Protein class

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

Subcellular location

Nucleoplasm,Nuclear membrane,Plasma membrane,Primary cilium,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

809 residues, UniProt reviewed canonical sequence.

>Q08499|PDE4D
     1  MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL LHPHHHLPPP
    61  PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA TGRVRHRGYS DTERYLYCRA
   121  MDRTSYAVET GHRPGLKKSR MSWPSSFQGL RRFDVDNGTS AGRSPLDPMT SPGSGLILQA
   181  NFVHSQRRES FLYRSDSDYD LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF
   241  AALTNLQDRA PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV
   301  SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT QKEKEKKKRP
   361  MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED VNKWGLHVFR IAELSGNRPL
   421  TVIMHTIFQE RDLLKTFKIP VDTLITYLMT LEDHYHADVA YHNNIHAADV VQSTHVLLST
   481  PALEAVFTDL EILAAIFASA IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF
   541  KLLQEENCDI FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL
   601  LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER ERGMEISPMC
   661  DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT LEDNREWYQS TIPQSPSPAP
   721  DDPEEGRQGQ TEKFQFELTL EEDGESDTEK DSGSQVEEDT SCSDSKTLCT QDSESTEIPL
   781  DEQVEEEAVG EEEESQPEAC VIDDRSPDT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDE4D 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

71 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDE4D.

Disease | AllUniProt

Conditions PDE4D is implicated in, by any mechanism.

• Acrodysostosis 2, with or without hormone resistance (ACRDYS2) MIM:614613

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 669 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acrodysostosis 2 with or without hormone resistance
• Metaphyseal acroscyphodysplasia

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

3.75

DepMap mean gene effect

-0.02

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

• adrenergic receptor signaling pathway
• cAMP catabolic process
• cellular response to cAMP
• cellular response to epinephrine stimulus
• establishment of endothelial barrier
• negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• negative regulation of cAMP/PKA signal transduction
• negative regulation of heart contraction
• negative regulation of relaxation of cardiac muscle
• positive regulation of heart rate
• positive regulation of interleukin-2 production
• positive regulation of interleukin-5 production
• positive regulation of type II interferon production
• regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
• regulation of cardiac muscle cell contraction
• regulation of cell communication by electrical coupling involved in cardiac conduction
• regulation of heart rate
• regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• T cell receptor signaling pathway

Molecular functions

• 3',5'-cyclic-AMP phosphodiesterase activity
• 3',5'-cyclic-GMP phosphodiesterase activity
• 3',5'-cyclic-nucleotide phosphodiesterase activity
• ATPase binding
• beta-2 adrenergic receptor binding
• calcium channel regulator activity
• cAMP binding
• enzyme binding
• heterocyclic compound binding
• metal ion binding
• scaffold protein binding
• signaling receptor regulator activity
• transmembrane transporter binding

Cellular components

• apical plasma membrane
• calcium channel complex
• centrosome
• cilium
• cytosol
• membrane
• nuclear membrane
• nucleoplasm
• plasma membrane
• voltage-gated calcium channel complex

Protein domainsUniProt · Pfam · InterPro

• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain
• 3'5'-cyclic nucleotide phosphodiesterase
• 3'5'-cyclic nucleotide phosphodiesterase, conserved site
• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily
• Phosphodiesterase 4 upstream conserved regions (UCR)
• 3'5'-cyclic nucleotide phosphodiesterase
• Phosphodiesterase 4 upstream conserved regions (UCR)

KeywordsUniProt

• cAMP
• Cell membrane
• Cytoplasm
• Cytoskeleton
• Hydrolase
• Isopeptide bond
• Manganese
• Membrane
• Metal-binding
• Phosphoprotein
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of PDE4D in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PDE4DIP
• ARRB1
• HSPB6
• ARRB2