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    SMPD4 sphingomyelin phosphodiesterase 4 [ Homo sapiens (human) ]

    Gene ID: 55627, updated on 7-Apr-2024

    Summary

    Official Symbol
    SMPD4provided by HGNC
    Official Full Name
    sphingomyelin phosphodiesterase 4provided by HGNC
    Primary source
    HGNC:HGNC:32949
    See related
    Ensembl:ENSG00000136699 MIM:610457; AllianceGenome:HGNC:32949
    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
    SKNY; NET13; NEDMABA; NEDMEBA; NSMASE3; NSMASE-3
    Summary
    The protein encoded by this gene is a sphingomyelinase that catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. This gene is activated by DNA damage, cellular stress, and tumor necrosis factor, but it is downregulated by wild-type p53. The encoded protein localizes to the endoplasmic reticulum and Golgi network. [provided by RefSeq, Mar 2017]
    Expression
    Ubiquitous expression in bone marrow (RPKM 16.4), testis (RPKM 14.6) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SMPD4 in Genome Data Viewer
    Location:
    2q21.1
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (130151392..130181757, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (130585291..130615727, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (130908965..130939330, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene POTE ankyrin domain family member F Neighboring gene RNA, U6 small nuclear 1049, pseudogene Neighboring gene POTEF antisense RNA 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:130886707-130887281 Neighboring gene mediator complex subunit 15 pseudogene 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16521 Neighboring gene coiled-coil domain containing 74B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16523 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:130917957-130918586 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:130921824-130922007 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:130938087-130938883 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11953 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11954 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:130940784-130941520 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:130941521-130942257 Neighboring gene mitotic spindle organizing protein 2B Neighboring gene tubulin alpha 3e Neighboring gene ras homolog family member Q pseudogene 3

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 binding to CXCR4 induces NADPH oxidase-mediated production of superoxide radicals in neurons, which is involved in the activation of neutral sphingomyelinase PubMed
    env In human primary neurons, HIV-1 gp120 induces the activation of sphingomyelinases (primarily neutral sphingomyelinase); antisense knockdown of neutral sphingomyelinase markedly inhibits gp120-mediated apoptosis and cell death of primary neurons PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ20297, FLJ20756, KIAA1418

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables sphingomyelin phosphodiesterase D activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables sphingomyelin phosphodiesterase D activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables sphingomyelin phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    located_in nuclear envelope ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in nuclear outer membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in sarcolemma ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in trans-Golgi network IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    sphingomyelin phosphodiesterase 4
    Names
    neutral sphingomyelinase 3
    neutral sphingomyelinase III
    sphingomyelin phosphodiesterase 4, neutral membrane (neutral sphingomyelinase-3)
    NP_001164554.1
    NP_060221.2
    NP_060421.3
    XP_011509745.1
    XP_011509746.1
    XP_024308746.1
    XP_047300894.1
    XP_054188850.1
    XP_054188851.1
    XP_054188852.1
    XP_054188853.1
    XP_054188854.1
    XP_054188855.1
    XP_054188856.1
    XP_054188857.1
    XP_054188858.1
    XP_054188859.1
    XP_054198841.1
    XP_054198842.1
    XP_054198843.1
    XP_054198844.1
    XP_054198845.1
    XP_054198846.1
    XP_054198847.1
    XP_054198848.1
    XP_054198849.1
    XP_054198850.1

    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_053070.1 RefSeqGene

      Range
      6149..36343
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001171083.2NP_001164554.1  sphingomyelin phosphodiesterase 4 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate exons resulting in the loss of an in-frame segment in the 5' coding region, and it also lacks an alternate in-frame exon in the central coding region, compared to variant 2. The resulting isoform (3) is shorter than isoform 2.
      Source sequence(s)
      AC018804, AI393912, AK299185, DA797873
      Consensus CDS
      CCDS54398.1
      UniProtKB/Swiss-Prot
      B1PBA3, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9NXE4, Q9P2C9
      Related
      ENSP00000405187.2, ENST00000431183.6
      Conserved Domains (1) summary
      pfam14724
      Location:47709
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase
    2. NM_017751.4NP_060221.2  sphingomyelin phosphodiesterase 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks an alternate in-frame exon in the central coding region, compared to variant 2, resulting in an isoform (1) that is shorter than isoform 2.
      Source sequence(s)
      AI393912, AK000304, DA797873
      Consensus CDS
      CCDS2156.2
      UniProtKB/Swiss-Prot
      B1PBA3, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9NXE4, Q9P2C9
      Related
      ENSP00000259217.8, ENST00000351288.10
      Conserved Domains (1) summary
      pfam14724
      Location:47782
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase
    3. NM_017951.5NP_060421.3  sphingomyelin phosphodiesterase 4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (2).
      Source sequence(s)
      AC018804
      Consensus CDS
      CCDS42751.2
      UniProtKB/Swiss-Prot
      B1PBA3, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9NXE4, Q9P2C9
      UniProtKB/TrEMBL
      A0A7P0TB24
      Related
      ENSP00000506463.1, ENST00000680298.1
      Conserved Domains (1) summary
      pfam14724
      Location:8772
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase

    RNA

    1. NR_033231.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an alternate internal exon in the 5' region, compared to variant 2. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 2, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC018804, AI393912, BC064947, DA797873
      Related
      ENST00000454468.5
    2. NR_033232.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an alternate internal exon in both the 5' and central regions, compared to variant 2. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 2, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC018804, AI393912, AK303519, DA797873
      Related
      ENST00000412570.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      130151392..130181757 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011511444.4XP_011509746.1  sphingomyelin phosphodiesterase 4 isoform X2

      UniProtKB/Swiss-Prot
      B1PBA3, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9NXE4, Q9P2C9
      Conserved Domains (1) summary
      pfam14724
      Location:125860
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase
    2. XM_011511443.3XP_011509745.1  sphingomyelin phosphodiesterase 4 isoform X1

      UniProtKB/Swiss-Prot
      B1PBA3, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9NXE4, Q9P2C9
      Conserved Domains (1) summary
      pfam14724
      Location:125889
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase
    3. XM_047444938.1XP_047300894.1  sphingomyelin phosphodiesterase 4 isoform X3

      Related
      ENSP00000401648.1, ENST00000439886.5
    4. XM_024452978.2XP_024308746.1  sphingomyelin phosphodiesterase 4 isoform X4

      Conserved Domains (1) summary
      pfam14724
      Location:97552
      mit_SMPDase; Mitochondrial-associated sphingomyelin phosphodiesterase

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_025791762.1 Reference GRCh38.p14 PATCHES

      Range
      327940..358309 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054332880.1XP_054188855.1  sphingomyelin phosphodiesterase 4 isoform X8

    2. XM_054332879.1XP_054188854.1  sphingomyelin phosphodiesterase 4 isoform X7

    3. XM_054332878.1XP_054188853.1  sphingomyelin phosphodiesterase 4 isoform X2

    4. XM_054332876.1XP_054188851.1  sphingomyelin phosphodiesterase 4 isoform X6

    5. XM_054332877.1XP_054188852.1  sphingomyelin phosphodiesterase 4 isoform X1

    6. XM_054332875.1XP_054188850.1  sphingomyelin phosphodiesterase 4 isoform X5

    7. XM_054332881.1XP_054188856.1  sphingomyelin phosphodiesterase 4 isoform X9

    8. XM_054332883.1XP_054188858.1  sphingomyelin phosphodiesterase 4 isoform X4

    9. XM_054332882.1XP_054188857.1  sphingomyelin phosphodiesterase 4 isoform X10

    10. XM_054332884.1XP_054188859.1  sphingomyelin phosphodiesterase 4 isoform X11

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      130585291..130615727 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342867.1XP_054198842.1  sphingomyelin phosphodiesterase 4 isoform X13

    2. XM_054342866.1XP_054198841.1  sphingomyelin phosphodiesterase 4 isoform X12

    3. XM_054342869.1XP_054198844.1  sphingomyelin phosphodiesterase 4 isoform X2

    4. XM_054342868.1XP_054198843.1  sphingomyelin phosphodiesterase 4 isoform X1

    5. XM_054342871.1XP_054198846.1  sphingomyelin phosphodiesterase 4 isoform X15

    6. XM_054342870.1XP_054198845.1  sphingomyelin phosphodiesterase 4 isoform X14

    7. XM_054342872.1XP_054198847.1  sphingomyelin phosphodiesterase 4 isoform X16

    8. XM_054342874.1XP_054198849.1  sphingomyelin phosphodiesterase 4 isoform X4

    9. XM_054342873.1XP_054198848.1  sphingomyelin phosphodiesterase 4 isoform X17

    10. XM_054342875.1XP_054198850.1  sphingomyelin phosphodiesterase 4 isoform X18

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001171084.1: Suppressed sequence

      Description
      NM_001171084.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.