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    PDE4C phosphodiesterase 4C [ Homo sapiens (human) ]

    Gene ID: 5143, updated on 2-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 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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    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)

    Genotypes

    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
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in perinuclear region of cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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