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    SMPDL3A sphingomyelin phosphodiesterase acid like 3A [ Homo sapiens (human) ]

    Gene ID: 10924, updated on 27-Nov-2024

    Summary

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    Official Symbol
    SMPDL3Aprovided by HGNC
    Official Full Name
    sphingomyelin phosphodiesterase acid like 3Aprovided by HGNC
    Primary source
    HGNC:HGNC:17389
    See related
    Ensembl:ENSG00000172594 MIM:610728; AllianceGenome:HGNC:17389
    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
    ASM3A; ASML3a; yR36GH4.1
    Summary
    Enables phosphoric diester hydrolase activity and zinc ion binding activity. Involved in negative regulation of cGAS/STING signaling pathway and nucleoside triphosphate catabolic process. Located in extracellular exosome. Is active in extracellular space. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in colon (RPKM 18.5), small intestine (RPKM 18.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SMPDL3A in Genome Data Viewer
    Location:
    6q22.31
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (122789258..122809720)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (123977551..123998013)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (123110403..123130865)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:123076853-123077432 Neighboring gene RNA, 7SL, cytoplasmic 564, pseudogene Neighboring gene fatty acid binding protein 7 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:123110213-123110714 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:123110715-123111214 Neighboring gene Sharpr-MPRA regulatory region 4155 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_89596 Neighboring gene Sharpr-MPRA regulatory region 10347 Neighboring gene MPRA-validated peak6080 silencer Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:123141927-123142470 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:123142471-123143014 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:123165703-123166295 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:123166296-123166889 Neighboring gene ATP synthase membrane subunit g pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25022 Neighboring gene uncharacterized LOC124901392

    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. N-glycosylation of human sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is essential for stability, secretion and activity. Traini M, et al. Biochem J, 2017 Mar 8. PMID 28104755
    2. Regulation of sphingomyelin phosphodiesterase acid-like 3A gene (SMPDL3A) by liver X receptors. Noto PB, et al. Mol Pharmacol, 2012 Oct. PMID 22810003
    3. SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing. Hou Y, et al. Immunity, 2023 Nov 14. PMID 37890481
    4. Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor. Jeske J, et al. Biochem Pharmacol, 2017 Jul 15. PMID 28414139
    5. The structure and catalytic mechanism of human sphingomyelin phosphodiesterase like 3a--an acid sphingomyelinase homologue with a novel nucleotide hydrolase activity. Lim SM, et al. FEBS J, 2016 Mar. PMID 26783088

    See all (15) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Activation of pregnane X receptor induces SMPDL3A expression in primary hepatocytes.
      Title: Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor.
    2. Site-specific N-glycosylation is essential for the intracellular stability, secretion and activity of human SMPDL3A.
      Title: N-glycosylation of human sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is essential for stability, secretion and activity.
    3. Solved the structure of SMPDL3a revealing a calcineurin-like fold. A dimetal site, glycosylation pattern and a disulfide bond network are likely to be conserved also in aSMase. We show that the binuclear site of SMPDL3a is occupied by two Zn(2+) ions.
      Title: The structure and catalytic mechanism of human sphingomyelin phosphodiesterase like 3a--an acid sphingomyelinase homologue with a novel nucleotide hydrolase activity.
    4. Data indicate that sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a nucleotide phosphodiesterase secreted from cholesterol-loaded macrophages.
      Title: Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages.
    5. the induction of SMPDL3A is liver X receptor-dependent and is restricted to human blood cells with no induction observed in mouse cellular systems.
      Title: Regulation of sphingomyelin phosphodiesterase acid-like 3A gene (SMPDL3A) by liver X receptors.
    6. ASML3a is involved in the process of bladder tumorigenesis
      Title: Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20177

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent H2AZ histone chaperone activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent H3-H4 histone complex chaperone activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA clamp loader activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables chromatin extrusion motor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cohesin loader activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphoric diester hydrolase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphoric diester hydrolase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphoric diester hydrolase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    NOT enables sphingomyelin phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chromatin looping IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cGAS/STING signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in nucleoside triphosphate catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in sphingomyelin catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular exosome HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in extracellular space IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in extracellular space IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cyclic GMP-AMP phosphodiesterase SMPDL3A
    Names
    0610010C24Rik
    2',3'-cGAMP phosphodiesterase SMPDL3A
    ASM-like phosphodiesterase 3a
    acid sphingomyelinase-like phosphodiesterase 3a
    NP_001273067.1
    NP_006705.1

    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.

    mRNA and Protein(s)

    1. NM_001286138.2 → NP_001273067.1  cyclic GMP-AMP phosphodiesterase SMPDL3A isoform b

      See identical proteins and their annotated locations for NP_001273067.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon in the 5' coding region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AK301365, DA510600, Y08136
      Consensus CDS
      CCDS69190.1
      UniProtKB/Swiss-Prot
      Q92484
      Related
      ENSP00000442152.1, ENST00000539041.5
      Conserved Domains (2) summary
      COG1409
      Location:13 → 206
      CpdA; 3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms]
      cd00842
      Location:1 → 205
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

    2. NM_006714.5 → NP_006705.1  cyclic GMP-AMP phosphodiesterase SMPDL3A isoform a precursor

      See identical proteins and their annotated locations for NP_006705.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      BC018999, DA510600, Y08136
      Consensus CDS
      CCDS5128.1
      UniProtKB/Swiss-Prot
      B7Z729, Q8WV13, Q92484
      Related
      ENSP00000357425.4, ENST00000368440.5
      Conserved Domains (1) summary
      cd00842
      Location:40 → 336
      MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      122789258..122809720
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      123977551..123998013
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92484.2 GenPept UniProtKB/Swiss-Prot:Q92484

    Gene LinkOut

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

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