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Protein

Acid sphingomyelinase-like phosphodiesterase 3a

Gene

SMPDL3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has in vitro nucleotide phosphodiesterase activity with nucleoside triphosphates, such as ATP (PubMed:25288789, PubMed:26783088). Has in vitro activity with p-nitrophenyl-TMP (PubMed:25288789). Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates (PubMed:25288789, PubMed:26783088). Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine (PubMed:26783088). Does not have sphingomyelin phosphodiesterase activity (PubMed:25288789, PubMed:26783088).2 Publications

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ per subunit.1 Publication

Enzyme regulationi

Requires micromolar levels of Zn2+ for activity (PubMed:26783088). Inhibited by millimolar levels of Zn2+ (PubMed:25288789, PubMed:26783088).2 Publications

Kineticsi

  1. KM=326 µM for ATP1 Publication
  2. KM=306 µM for ADP1 Publication
  3. KM=348 µM for ADP-ribose1 Publication
  4. KM=390 µM for CDP-ethanolamine1 Publication
  5. KM=262 µM for CDP-choline1 Publication

    pH dependencei

    Optimum pH is 4-6.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi45 – 451Zinc 11 Publication
    Metal bindingi47 – 471Zinc 11 Publication
    Metal bindingi110 – 1101Zinc 11 Publication
    Metal bindingi110 – 1101Zinc 21 Publication
    Binding sitei114 – 1141Substrate1 Publication
    Metal bindingi151 – 1511Zinc 21 Publication
    Binding sitei151 – 1511Substrate1 Publication
    Binding sitei152 – 1521Substrate1 Publication
    Metal bindingi252 – 2521Zinc 21 Publication
    Metal bindingi293 – 2931Zinc 21 Publication
    Metal bindingi295 – 2951Zinc 11 Publication

    GO - Molecular functioni

    • phosphoric diester hydrolase activity Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • nucleoside triphosphate catabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Acid sphingomyelinase-like phosphodiesterase 3a (EC:3.1.4.-2 Publications)
    Short name:
    ASM-like phosphodiesterase 3a
    Gene namesi
    Name:SMPDL3A
    Synonyms:ASML3A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:17389. SMPDL3A.

    Subcellular locationi

    GO - Cellular componenti

    • extracellular exosome Source: UniProtKB
    • extracellular space Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134932128.

    Polymorphism and mutation databases

    BioMutaiSMPDL3A.
    DMDMi39932730.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence analysisAdd
    BLAST
    Chaini23 – 453431Acid sphingomyelinase-like phosphodiesterase 3aPRO_0000002328Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi62 ↔ 81Combined sources
    Glycosylationi69 – 691N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi222 – 2221N-linked (GlcNAc...)1 Publication
    Glycosylationi238 – 2381N-linked (GlcNAc...)Sequence analysis
    Glycosylationi263 – 2631N-linked (GlcNAc...)1 Publication
    Glycosylationi356 – 3561N-linked (GlcNAc...)2 Publications
    Disulfide bondi420 ↔ 424Sequence analysis
    Disulfide bondi430 ↔ 443Combined sources
    Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence analysis

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiQ92484.
    PaxDbiQ92484.
    PeptideAtlasiQ92484.
    PRIDEiQ92484.

    PTM databases

    iPTMnetiQ92484.
    PhosphoSiteiQ92484.

    Expressioni

    Tissue specificityi

    Detected in blood serum. Detected in macrophages (at protein level).1 Publication

    Inductioni

    Up-regulated in macrophages in response to cholesterol accumulation. Up-regulated by cAMP.1 Publication

    Gene expression databases

    BgeeiENSG00000172594.
    CleanExiHS_SMPDL3A.
    GenevisibleiQ92484. HS.

    Organism-specific databases

    HPAiHPA030148.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi116128. 1 interaction.
    IntActiQ92484. 2 interactions.
    STRINGi9606.ENSP00000357425.

    Structurei

    Secondary structure

    1
    453
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi38 – 436Combined sources
    Helixi58 – 603Combined sources
    Helixi63 – 653Combined sources
    Helixi85 – 9713Combined sources
    Beta strandi103 – 1075Combined sources
    Helixi117 – 1193Combined sources
    Helixi122 – 13918Combined sources
    Beta strandi140 – 1423Combined sources
    Beta strandi145 – 1473Combined sources
    Beta strandi153 – 1564Combined sources
    Helixi166 – 17510Combined sources
    Turni176 – 1783Combined sources
    Helixi181 – 19010Combined sources
    Beta strandi193 – 1975Combined sources
    Beta strandi200 – 2078Combined sources
    Helixi210 – 2134Combined sources
    Helixi218 – 2203Combined sources
    Helixi226 – 2283Combined sources
    Helixi229 – 24214Combined sources
    Beta strandi246 – 2505Combined sources
    Beta strandi255 – 2573Combined sources
    Beta strandi261 – 2633Combined sources
    Beta strandi265 – 2673Combined sources
    Helixi269 – 28113Combined sources
    Turni282 – 2854Combined sources
    Beta strandi286 – 2916Combined sources
    Beta strandi298 – 3036Combined sources
    Beta strandi305 – 3073Combined sources
    Beta strandi309 – 3157Combined sources
    Beta strandi334 – 3407Combined sources
    Turni342 – 3443Combined sources
    Beta strandi347 – 3559Combined sources
    Helixi357 – 3637Combined sources
    Beta strandi368 – 3736Combined sources
    Helixi374 – 3785Combined sources
    Beta strandi381 – 3833Combined sources
    Helixi385 – 39511Combined sources
    Helixi401 – 41010Combined sources
    Turni411 – 4133Combined sources
    Helixi422 – 43312Combined sources
    Helixi437 – 4426Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    5EBBX-ray2.60A/B/C34-443[»]
    5EBEX-ray3.00A33-450[»]
    B/C33-447[»]
    ProteinModelPortaliQ92484.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the acid sphingomyelinase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG410ISVB. Eukaryota.
    ENOG410XRWF. LUCA.
    GeneTreeiENSGT00530000063095.
    HOGENOMiHOG000294197.
    HOVERGENiHBG050594.
    InParanoidiQ92484.
    KOiK01128.
    OMAiDLWKPWL.
    OrthoDBiEOG091G080M.
    PhylomeDBiQ92484.
    TreeFamiTF313674.

    Family and domain databases

    Gene3Di3.60.21.10. 1 hit.
    InterProiIPR017064. ASM-like_Pdiesterase_prd.
    IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    [Graphical view]
    PfamiPF00149. Metallophos. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036767. ASM-like_PDE. 1 hit.
    SUPFAMiSSF56300. SSF56300. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q92484-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MALVRALVCC LLTAWHCRSG LGLPVAPAGG RNPPPAIGQF WHVTDLHLDP
    60 70 80 90 100
    TYHITDDHTK VCASSKGANA SNPGPFGDVL CDSPYQLILS AFDFIKNSGQ
    110 120 130 140 150
    EASFMIWTGD SPPHVPVPEL STDTVINVIT NMTTTIQSLF PNLQVFPALG
    160 170 180 190 200
    NHDYWPQDQL PVVTSKVYNA VANLWKPWLD EEAISTLRKG GFYSQKVTTN
    210 220 230 240 250
    PNLRIISLNT NLYYGPNIMT LNKTDPANQF EWLESTLNNS QQNKEKVYII
    260 270 280 290 300
    AHVPVGYLPS SQNITAMREY YNEKLIDIFQ KYSDVIAGQF YGHTHRDSIM
    310 320 330 340 350
    VLSDKKGSPV NSLFVAPAVT PVKSVLEKQT NNPGIRLFQY DPRDYKLLDM
    360 370 380 390 400
    LQYYLNLTEA NLKGESIWKL EYILTQTYDI EDLQPESLYG LAKQFTILDS
    410 420 430 440 450
    KQFIKYYNYF FVSYDSSVTC DKTCKAFQIC AIMNLDNISY ADCLKQLYIK

    HNY
    Length:453
    Mass (Da):51,260
    Last modified:December 15, 2003 - v2
    Checksum:i2EFE762BF663984B
    GO
    Isoform 2 (identifier: Q92484-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-131: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:322
    Mass (Da):37,285
    Checksum:i46447C3855333A5F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti452 – 4521N → K in CAA69330 (Ref. 5) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161H → Y.
    Corresponds to variant rs12523814 [ dbSNP | Ensembl ].
    VAR_048338
    Natural varianti161 – 1611P → S.
    Corresponds to variant rs28385609 [ dbSNP | Ensembl ].
    VAR_048339

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 131131Missing in isoform 2. 1 PublicationVSP_054640Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK301365 mRNA. Translation: BAH13465.1.
    AL732431 Genomic DNA. Translation: CAI23631.1.
    CH471051 Genomic DNA. Translation: EAW48164.1.
    BC018999 mRNA. Translation: AAH18999.1.
    Y08136 mRNA. Translation: CAA69330.1.
    CCDSiCCDS5128.1. [Q92484-1]
    CCDS69190.1. [Q92484-2]
    RefSeqiNP_001273067.1. NM_001286138.1. [Q92484-2]
    NP_006705.1. NM_006714.4. [Q92484-1]
    UniGeneiHs.486357.

    Genome annotation databases

    EnsembliENST00000368440; ENSP00000357425; ENSG00000172594. [Q92484-1]
    ENST00000539041; ENSP00000442152; ENSG00000172594. [Q92484-2]
    GeneIDi10924.
    KEGGihsa:10924.
    UCSCiuc003pzg.5. human. [Q92484-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK301365 mRNA. Translation: BAH13465.1.
    AL732431 Genomic DNA. Translation: CAI23631.1.
    CH471051 Genomic DNA. Translation: EAW48164.1.
    BC018999 mRNA. Translation: AAH18999.1.
    Y08136 mRNA. Translation: CAA69330.1.
    CCDSiCCDS5128.1. [Q92484-1]
    CCDS69190.1. [Q92484-2]
    RefSeqiNP_001273067.1. NM_001286138.1. [Q92484-2]
    NP_006705.1. NM_006714.4. [Q92484-1]
    UniGeneiHs.486357.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    5EBBX-ray2.60A/B/C34-443[»]
    5EBEX-ray3.00A33-450[»]
    B/C33-447[»]
    ProteinModelPortaliQ92484.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116128. 1 interaction.
    IntActiQ92484. 2 interactions.
    STRINGi9606.ENSP00000357425.

    PTM databases

    iPTMnetiQ92484.
    PhosphoSiteiQ92484.

    Polymorphism and mutation databases

    BioMutaiSMPDL3A.
    DMDMi39932730.

    Proteomic databases

    MaxQBiQ92484.
    PaxDbiQ92484.
    PeptideAtlasiQ92484.
    PRIDEiQ92484.

    Protocols and materials databases

    DNASUi10924.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000368440; ENSP00000357425; ENSG00000172594. [Q92484-1]
    ENST00000539041; ENSP00000442152; ENSG00000172594. [Q92484-2]
    GeneIDi10924.
    KEGGihsa:10924.
    UCSCiuc003pzg.5. human. [Q92484-1]

    Organism-specific databases

    CTDi10924.
    GeneCardsiSMPDL3A.
    HGNCiHGNC:17389. SMPDL3A.
    HPAiHPA030148.
    MIMi610728. gene.
    neXtProtiNX_Q92484.
    PharmGKBiPA134932128.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410ISVB. Eukaryota.
    ENOG410XRWF. LUCA.
    GeneTreeiENSGT00530000063095.
    HOGENOMiHOG000294197.
    HOVERGENiHBG050594.
    InParanoidiQ92484.
    KOiK01128.
    OMAiDLWKPWL.
    OrthoDBiEOG091G080M.
    PhylomeDBiQ92484.
    TreeFamiTF313674.

    Miscellaneous databases

    ChiTaRSiSMPDL3A. human.
    GenomeRNAii10924.
    PROiQ92484.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000172594.
    CleanExiHS_SMPDL3A.
    GenevisibleiQ92484. HS.

    Family and domain databases

    Gene3Di3.60.21.10. 1 hit.
    InterProiIPR017064. ASM-like_Pdiesterase_prd.
    IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    [Graphical view]
    PfamiPF00149. Metallophos. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036767. ASM-like_PDE. 1 hit.
    SUPFAMiSSF56300. SSF56300. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiASM3A_HUMAN
    AccessioniPrimary (citable) accession number: Q92484
    Secondary accession number(s): B7Z729, Q8WV13
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 29, 2001
    Last sequence update: December 15, 2003
    Last modified: September 7, 2016
    This is version 117 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.