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    PDE2A phosphodiesterase 2A [ Homo sapiens (human) ]

    Gene ID: 5138, updated on 14-Nov-2024

    Summary

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    Official Symbol
    PDE2Aprovided by HGNC
    Official Full Name
    phosphodiesterase 2Aprovided by HGNC
    Primary source
    HGNC:HGNC:8777
    See related
    Ensembl:ENSG00000186642 MIM:602658; AllianceGenome:HGNC:8777
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PDE2A1; PED2A4; cGSPDE; CGS-PDE; IDDPADS
    Summary
    Enables several functions, including 3',5'-cyclic-nucleotide phosphodiesterase activity; anion binding activity; and metal ion binding activity. Involved in several processes, including intracellular signaling cassette; regulation of signal transduction; and regulation of vascular permeability. Located in several cellular components, including cytosol; mitochondrial membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in spleen (RPKM 45.0), brain (RPKM 27.8) and 14 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PDE2A in Genome Data Viewer
    Location:
    11q13.4
    Exon count:
    35
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (72576141..72674422, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (72502658..72602659, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (72287185..72385466, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene cyclic nucleotide gated channel subunit alpha 1 pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr11:72273300-72273507 Neighboring gene long intergenic non-protein coding RNA 1537 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72295333-72295856 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72295857-72296378 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3721 Neighboring gene PDE2A antisense RNA 2 Neighboring gene uncharacterized LOC105369377 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72329425-72329944 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72336883-72337427 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72337428-72337971 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72339671-72340196 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72340723-72341248 Neighboring gene RNA, U7 small nuclear 105 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72341249-72341773 Neighboring gene microRNA 139 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72344820-72345416 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72345417-72346012 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72353123-72353623 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72354058-72354647 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72363808-72364353 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72367701-72368202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72373037-72373701 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72375031-72375693 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72379106-72379610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5193 Neighboring gene PDE2A antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72384035-72384661 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72384662-72385287 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72385288-72385914 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72385915-72386539 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72386690-72387190 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3723 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72391485-72392310 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72395779-72396338 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3724 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72415096-72415932 Neighboring gene ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72417010-72417596 Neighboring gene ARAP1 antisense RNA 2 Neighboring gene ribosomal protein S12 pseudogene 20

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders.
      Title: Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders.
    2. The phosphodiesterase 2A controls lymphatic junctional maturation via cGMP-dependent notch signaling.
      Title: The phosphodiesterase 2A controls lymphatic junctional maturation via cGMP-dependent notch signaling.
    3. Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma.
      Title: Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma.
    4. miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/beta-catenin signaling.
      Title: miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/β-catenin signaling.
    5. Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.
      Title: Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.
    6. Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.
      Title: Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.
    7. A Novel Inhibition Modality for Phosphodiesterase 2A.
      Title: A Novel Inhibition Modality for Phosphodiesterase 2A.
    8. Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy.
      Title: Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy.
    9. Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.
      Title: Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.
    10. A Homozygous Splicing Mutation in PDE2A in a Family With Atypical Rett Syndrome.
      Title: A Homozygous Splicing Mutation in PDE2A in a Family With Atypical Rett Syndrome.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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

    Associated conditions

    Description Tests
    Intellectual developmental disorder with paroxysmal dyskinesia or seizures
    MedGen: C5436894 OMIM: 619150 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.
    EBI GWAS Catalog
    Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.
    EBI GWAS Catalog

    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 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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3',5'-cGMP-inhibited cyclic-nucleotide phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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-GMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cyclic-GMP phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables TPR domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables cAMP binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cGMP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cGMP binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphate ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within aorta development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cAMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cGMP catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cGMP catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cGMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cGMP-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to 2,3,7,8-tetrachlorodibenzodioxine IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to cAMP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to cGMP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to granulocyte macrophage colony-stimulating factor stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to macrophage colony-stimulating factor stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to mechanical stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cellular response to transforming growth factor beta stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in cellular response to xenobiotic stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in establishment of endothelial barrier ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_or_within heart valve development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in monocyte differentiation IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of cAMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of cGMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of vascular permeability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of gene expression IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of vascular permeability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cGMP-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of mitochondrion organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within ventricular septum development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in mitochondrial inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in mitochondrial outer membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial outer membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in perinuclear region of cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in presynaptic membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in synaptic membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    cGMP-dependent 3',5'-cyclic phosphodiesterase
    Names
    cGMP-stimulated phosphodiesterase 1
    cGMP-stimulated phosphodiesterase 2
    cGMP-stimulated phosphodiesterase 4
    cyclic GMP-stimulated phosphodiesterase
    phosphodiesterase 2A, cGMP-stimulated
    NP_001137311.1
    NP_001139681.1
    NP_001230713.1
    NP_002590.1
    XP_005274097.1
    XP_054225080.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001143839.4 → NP_001137311.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (PDE2A2) is shorter and has a distinct N-terminus, compared to isoform PDE2A3. This variant (2) is assembled from partial human transcripts. The full-length exon combination is inferred from the mouse ortholog (NM_001143849.1, see PMID: 21724846)
      Source sequence(s)
      AP003065, AP005019
      Consensus CDS
      CCDS44670.1
      UniProtKB/TrEMBL
      Q8IW54
      Related
      ENSP00000442256.1, ENST00000544570.5
      Conserved Domains (2) summary
      smart00065
      Location:402 → 551
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:648 → 878
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    2. NM_001146209.3 → NP_001139681.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform, PDE2A4 (AY495087.1), is shorter and has a distinct N-terminus, compared to isoform PDE2A3.
      Source sequence(s)
      AP003065, AP005019
      Consensus CDS
      CCDS53678.1
      UniProtKB/TrEMBL
      Q8IW54
      Related
      ENSP00000446399.1, ENST00000540345.5
      Conserved Domains (2) summary
      smart00065
      Location:400 → 549
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:646 → 879
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    3. NM_001243784.2 → NP_001230713.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A1

      See identical proteins and their annotated locations for NP_001230713.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (PDE2A1) is shorter and has a distinct N-terminus, compared to isoform 1. This variant (2) is assembled from partial human transcripts. The full-length exon combination is inferred from the mouse ortholog (NM_001243757.1, see PMID: 19632989)
      Source sequence(s)
      AP003065, AP005019
      Consensus CDS
      CCDS73345.1
      UniProtKB/TrEMBL
      Q8IW54
      Related
      ENSP00000411657.3, ENST00000444035.6
      Conserved Domains (2) summary
      smart00065
      Location:388 → 537
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:634 → 867
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    4. NM_002599.5 → NP_002590.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A3

      See identical proteins and their annotated locations for NP_002590.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform, PDE2A3 (see PMID:9210593).
      Source sequence(s)
      AP003065, AP005019
      Consensus CDS
      CCDS8216.1
      UniProtKB/Swiss-Prot
      B2R646, B3KRV5, E9PGI1, F6W5Z0, O00408, Q5J791, Q5J792, Q5J793, Q6ZMR1
      UniProtKB/TrEMBL
      Q8IW54
      Related
      ENSP00000334910.5, ENST00000334456.10
      Conserved Domains (2) summary
      smart00065
      Location:409 → 558
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:655 → 885
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      72576141..72674422 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005274040.4 → XP_005274097.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1

      UniProtKB/TrEMBL
      Q8IW54
      Conserved Domains (2) summary
      smart00065
      Location:408 → 557
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:654 → 887
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      72502658..72602659 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369105.1 → XP_054225080.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00408.1 GenPept UniProtKB/Swiss-Prot:O00408

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
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