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PDE4C phosphodiesterase 4C [ Homo sapiens (human) ]

Gene ID: 5143, updated on 27-Nov-2024

Summary

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Official Symbol
PDE4Cprovided by HGNC
Official Full Name
phosphodiesterase 4Cprovided by HGNC
Primary source
HGNC:HGNC:8782
See related
Ensembl:ENSG00000105650 MIM:600128; AllianceGenome:HGNC:8782
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DPDE1; PDE21
Summary
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]
Expression
Broad expression in placenta (RPKM 1.5), endometrium (RPKM 1.5) and 20 other tissues See more
Orthologs
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Genomic context

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See PDE4C in Genome Data Viewer
Location:
19p13.11
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (18207965..18255362, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (18342065..18389460, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (18318775..18366172, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene MPV17 mitochondrial inner membrane protein like 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18314094-18314876 Neighboring gene Sharpr-MPRA regulatory region 13953 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14306 Neighboring gene uncharacterized LOC102725254 Neighboring gene RAB3A, member RAS oncogene family Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10379 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr19:18330099-18331298 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10380 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14307 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10381 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18342361-18343052 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18359151-18360054 Neighboring gene colon, intestine and stomach enriched 1 Neighboring gene IQ motif containing N Neighboring gene Sharpr-MPRA regulatory region 4774 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14309 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14310 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10383 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18391566-18392417 Neighboring gene JunD proto-oncogene, AP-1 transcription factor subunit

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C). Engels P, et al. FEBS Lett, 1995 Jan 30. PMID 7843419
  2. Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain. Pérez-Torres S, et al. J Chem Neuroanat, 2000 Dec. PMID 11207431
  3. Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma. Pan F, et al. J Cell Mol Med, 2024 May. PMID 38774995, Free PMC Article
  4. Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma. Bao Z, et al. Oncol Rep, 2014 Jul. PMID 24842301
  5. Multiple splice variants of phosphodiesterase PDE4C cloned from human lung and testis. Obernolte R, et al. Biochim Biophys Acta, 1997 Sep 12. PMID 9349724

See all (28) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma.
    Title: Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma.
  2. Data show that PDE4C is downregulated through promoter hypermethylation in glioma.
    Title: Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma.
  3. PDE4A and PDE4C work in redundant fashion to mediate the loss of inhibitory PGE2 signaling in lung fibroblasts.
    Title: Attenuation of inhibitory prostaglandin E2 signaling in human lung fibroblasts is mediated by phosphodiesterase 4.
  4. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
  5. Observational study of gene-disease association. (HuGE Navigator)
    Title: New genetic associations detected in a host response study to hepatitis B vaccine.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity PubMed
tat HIV-1 Tat decreases the intracellular levels of cAMP and CREB ser-133 phosphorylation through a signal transduction pathway involving sequential activation of phosphatidylinositol 3-kinase, AKT, and cyclic nucleoside phosphodiesterases PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Readthrough PDE4C

Included gene: CIST1

Homology

Clone Names

  • FLJ38065, MGC126222

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3',5'-cyclic-AMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 3',5'-cyclic-AMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 3',5'-cyclic-AMP phosphodiesterase activity TAS
Traceable Author Statement
more info
  
enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cAMP catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cAMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in cilium ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular space HDA PubMed 

General protein information

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Preferred Names
3',5'-cyclic-AMP phosphodiesterase 4C
Names
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
cAMP-specific phosphodiesterase 4C
dunce-like phosphodiesterase E1
phosphodiesterase 4C, cAMP-specific (phosphodiesterase E1 dunce homolog, Drosophila)
NP_000914.2
NP_001092288.1
NP_001092289.1
NP_001317101.1
NP_001356630.1
NP_001382203.1
NP_001401409.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029629.1 RefSeqGene

    Range
    26763..45236
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000923.6 → NP_000914.2  3',5'-cyclic-AMP phosphodiesterase 4C isoform 1

    See identical proteins and their annotated locations for NP_000914.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC068499, BC109067, DB313915, L20968, U66346, Z46632
    Consensus CDS
    CCDS12373.1
    UniProtKB/Swiss-Prot
    B3KTC4, Q08493, Q9UN44, Q9UN45, Q9UN46, Q9UPJ6
    UniProtKB/TrEMBL
    O76105
    Related
    ENSP00000469696.1, ENST00000594617.7
    Conserved Domains (1) summary
    pfam00233
    Location:387 → 628
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  2. NM_001098818.4 → NP_001092288.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 3

    See identical proteins and their annotated locations for NP_001092288.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a shorter, distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC068499, BC109067, DB313915, L20968, U88713, Z46632
    Consensus CDS
    CCDS42523.1
    UniProtKB/TrEMBL
    B7Z6V2
    Related
    ENSP00000262805.10, ENST00000262805.17
    Conserved Domains (1) summary
    pfam00233
    Location:355 → 596
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  3. NM_001098819.4 → NP_001092289.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 2

    See identical proteins and their annotated locations for NP_001092289.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1. Variants 2 and 6 both encode the same isoform (2).
    Source sequence(s)
    AC068499, BC109067, DB313915, L20968, U88712, Z46632
    Consensus CDS
    CCDS46016.1
    UniProtKB/TrEMBL
    Q7KYS4
    Related
    ENSP00000402091.1, ENST00000447275.7
    Conserved Domains (2) summary
    pfam00233
    Location:281 → 522
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam18100
    Location:46 → 162
    PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

  4. NM_001330172.2 → NP_001317101.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC005759, AC008397, AC068499
    Consensus CDS
    CCDS12373.1
    UniProtKB/Swiss-Prot
    B3KTC4, Q08493, Q9UN44, Q9UN45, Q9UN46, Q9UPJ6
    UniProtKB/TrEMBL
    O76105
    Related
    ENSP00000470210.1, ENST00000594465.7

  5. NM_001369701.2 → NP_001356630.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC005759, AC068499
    Consensus CDS
    CCDS92567.1
    UniProtKB/TrEMBL
    O43850, Q32MM7
    Related
    ENSP00000439470.1, ENST00000539010.5
    Conserved Domains (1) summary
    pfam00233
    Location:156 → 397
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  6. NM_001395274.1 → NP_001382203.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC005759, AC068499
    Consensus CDS
    CCDS46016.1
    UniProtKB/TrEMBL
    Q7KYS4
    Conserved Domains (2) summary
    pfam00233
    Location:281 → 522
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam18100
    Location:46 → 162
    PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

  7. NM_001414480.1 → NP_001401409.1  3',5'-cyclic-AMP phosphodiesterase 4C isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC005759, AC008397, AC068499
    UniProtKB/Swiss-Prot
    B3KTC4, Q08493, Q9UN44, Q9UN45, Q9UN46, Q9UPJ6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    18207965..18255362 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    18342065..18389460 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NR_040546.1: Suppressed sequence

    Description
    NR_040546.1: This RefSeq was removed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q08493.2 GenPept UniProtKB/Swiss-Prot:Q08493

Gene LinkOut

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