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Protein

Acid sphingomyelinase-like phosphodiesterase 3a

Gene

Smpdl3a

Organism
Mus musculus (Mouse)
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:26792860). Has in vitro activity with p-nitrophenyl-TMP. Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates. Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine. Does not have sphingomyelin phosphodiesterase activity (By similarity).By similarity1 Publication

Cofactori

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

Enzyme regulationi

Requires micromolar levels of Zn2+ for activity. Inhibited by millimolar levels of Zn2+.1 Publication

Kineticsi

  1. KM=107 µM for ATP at pH 51 Publication
  2. KM=330 µM for ATP at pH 7.51 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi42 – 421Zinc 11 Publication
    Metal bindingi44 – 441Zinc 11 Publication
    Metal bindingi107 – 1071Zinc 11 Publication
    Metal bindingi107 – 1071Zinc 21 Publication
    Binding sitei111 – 1111Substrate1 Publication
    Metal bindingi148 – 1481Zinc 21 Publication
    Binding sitei148 – 1481Substrate1 Publication
    Binding sitei149 – 1491Substrate1 Publication
    Metal bindingi249 – 2491Zinc 21 Publication
    Binding sitei257 – 2571Substrate1 Publication
    Metal bindingi290 – 2901Zinc 21 Publication
    Metal bindingi292 – 2921Zinc 11 Publication

    GO - Molecular functioni

    GO - Biological processi

    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.-1 Publication)
    Short name:
    ASM-like phosphodiesterase 3a
    Gene namesi
    Name:Smpdl3a
    Synonyms:Asml3a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:1931437. Smpdl3a.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi111 – 1111H → A or Q: Abolishes enzyme activity. 1 Publication
    Mutagenesisi149 – 1491H → A: Abolishes enzyme activity. 1 Publication
    Mutagenesisi149 – 1491H → Q: Nearly abolishes enzyme activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence analysisAdd
    BLAST
    Chaini23 – 445423Acid sphingomyelinase-like phosphodiesterase 3aPRO_0000002329Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi59 ↔ 781 Publication
    Glycosylationi66 – 661N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi128 – 1281N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi219 – 2191N-linked (GlcNAc...)Sequence analysis
    Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi353 – 3531N-linked (GlcNAc...)Sequence analysis1 Publication
    Glycosylationi364 – 3641N-linked (GlcNAc...)Sequence analysis1 Publication
    Disulfide bondi417 ↔ 421Sequence analysis
    Disulfide bondi427 ↔ 4401 Publication

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiP70158.
    MaxQBiP70158.
    PaxDbiP70158.
    PRIDEiP70158.

    PTM databases

    iPTMnetiP70158.
    PhosphoSiteiP70158.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiP70158.
    CleanExiMM_SMPDL3A.
    ExpressionAtlasiP70158. baseline and differential.
    GenevisibleiP70158. MM.

    Interactioni

    Protein-protein interaction databases

    IntActiP70158. 2 interactions.
    MINTiMINT-4088461.
    STRINGi10090.ENSMUSP00000020022.

    Structurei

    Secondary structure

    1
    445
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi35 – 406Combined sources
    Helixi55 – 573Combined sources
    Helixi60 – 623Combined sources
    Helixi82 – 9413Combined sources
    Beta strandi100 – 1045Combined sources
    Helixi114 – 1163Combined sources
    Helixi119 – 13618Combined sources
    Beta strandi141 – 1444Combined sources
    Beta strandi150 – 1534Combined sources
    Helixi163 – 17210Combined sources
    Turni173 – 1753Combined sources
    Helixi178 – 18710Combined sources
    Beta strandi190 – 1934Combined sources
    Beta strandi200 – 2045Combined sources
    Helixi207 – 2104Combined sources
    Helixi215 – 2173Combined sources
    Helixi223 – 2253Combined sources
    Helixi226 – 23914Combined sources
    Beta strandi243 – 2508Combined sources
    Beta strandi252 – 2543Combined sources
    Beta strandi258 – 2603Combined sources
    Beta strandi262 – 2643Combined sources
    Helixi266 – 27813Combined sources
    Turni279 – 2824Combined sources
    Beta strandi283 – 2886Combined sources
    Beta strandi295 – 3006Combined sources
    Beta strandi306 – 3127Combined sources
    Beta strandi331 – 3377Combined sources
    Turni339 – 3413Combined sources
    Beta strandi344 – 3518Combined sources
    Helixi354 – 3607Combined sources
    Beta strandi366 – 3705Combined sources
    Helixi371 – 3755Combined sources
    Helixi382 – 39211Combined sources
    Helixi398 – 40710Combined sources
    Turni408 – 4103Combined sources
    Helixi419 – 43012Combined sources
    Helixi434 – 44411Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    5FC1X-ray1.39A23-445[»]
    5FC5X-ray1.68A23-445[»]
    5FC6X-ray1.66A23-445[»]
    5FC7X-ray1.46A23-445[»]
    5FCAX-ray1.92A/B23-445[»]
    5FCBX-ray1.55A23-445[»]
    ProteinModelPortaliP70158.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the acid sphingomyelinase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG410KDJ7. Eukaryota.
    ENOG410XRWF. LUCA.
    GeneTreeiENSGT00530000063095.
    HOGENOMiHOG000294197.
    HOVERGENiHBG050594.
    InParanoidiP70158.
    KOiK01128.
    OMAiDLWKPWL.
    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.

    Sequencei

    Sequence statusi: Complete.

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

    P70158-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MALLGNFLCC LLVAWLCGPG LGVPLAPADR APAVGQFWHV TDLHLDPTYH
    60 70 80 90 100
    ITDDRTKVCA SSKGANASNP GPFGDVLCDS PYQLILSAFD FIKNSGQEAS
    110 120 130 140 150
    FMIWTGDSPP HVPVPELSTG TVIKVITNMT MTVQNLFPNL QVFPALGNHD
    160 170 180 190 200
    YWPQDQLPIV TSKVYSAVAD LWKPWLGEEA ISTLKKGGFY SQKVASNPGL
    210 220 230 240 250
    RIISLNTNLY YGPNIMTLNK TDPANQFEWL ENTLNSSLWN KEKVYIIAHV
    260 270 280 290 300
    PVGYLPYATD TPAIRQYYNE KLLDIFRRYS SVIAGQFYGH THRDSLMVLS
    310 320 330 340 350
    DKNGNPLNSV FVAPAVTPVK GVLQKETNNP GVRLFQYKPG DYTLLDMVQY
    360 370 380 390 400
    YLNLTEANLK GESNWTLEYV LTQAYSVADL QPKSLYALVQ QFATKDSKQF
    410 420 430 440
    LKYYHYYFVS YDSSATCDQH CKTLQVCAIM NLDSMSYDDC LKQHL
    Length:445
    Mass (Da):49,858
    Last modified:July 27, 2011 - v2
    Checksum:i20D986E3463CB720
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y08135 mRNA. Translation: CAA69329.1.
    AK151683 mRNA. Translation: BAE30607.1.
    AK152282 mRNA. Translation: BAE31096.1.
    CH466540 Genomic DNA. Translation: EDL05124.1.
    BC139288 mRNA. Translation: AAI39289.1.
    BC139289 mRNA. Translation: AAI39290.1.
    CCDSiCCDS23857.1.
    RefSeqiNP_065586.3. NM_020561.2.
    UniGeneiMm.2379.

    Genome annotation databases

    EnsembliENSMUST00000020022; ENSMUSP00000020022; ENSMUSG00000019872.
    GeneIDi57319.
    KEGGimmu:57319.
    UCSCiuc007fcu.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y08135 mRNA. Translation: CAA69329.1.
    AK151683 mRNA. Translation: BAE30607.1.
    AK152282 mRNA. Translation: BAE31096.1.
    CH466540 Genomic DNA. Translation: EDL05124.1.
    BC139288 mRNA. Translation: AAI39289.1.
    BC139289 mRNA. Translation: AAI39290.1.
    CCDSiCCDS23857.1.
    RefSeqiNP_065586.3. NM_020561.2.
    UniGeneiMm.2379.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    5FC1X-ray1.39A23-445[»]
    5FC5X-ray1.68A23-445[»]
    5FC6X-ray1.66A23-445[»]
    5FC7X-ray1.46A23-445[»]
    5FCAX-ray1.92A/B23-445[»]
    5FCBX-ray1.55A23-445[»]
    ProteinModelPortaliP70158.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiP70158. 2 interactions.
    MINTiMINT-4088461.
    STRINGi10090.ENSMUSP00000020022.

    PTM databases

    iPTMnetiP70158.
    PhosphoSiteiP70158.

    Proteomic databases

    EPDiP70158.
    MaxQBiP70158.
    PaxDbiP70158.
    PRIDEiP70158.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000020022; ENSMUSP00000020022; ENSMUSG00000019872.
    GeneIDi57319.
    KEGGimmu:57319.
    UCSCiuc007fcu.1. mouse.

    Organism-specific databases

    CTDi10924.
    MGIiMGI:1931437. Smpdl3a.

    Phylogenomic databases

    eggNOGiENOG410KDJ7. Eukaryota.
    ENOG410XRWF. LUCA.
    GeneTreeiENSGT00530000063095.
    HOGENOMiHOG000294197.
    HOVERGENiHBG050594.
    InParanoidiP70158.
    KOiK01128.
    OMAiDLWKPWL.
    TreeFamiTF313674.

    Miscellaneous databases

    ChiTaRSiSmpdl3a. mouse.
    PROiP70158.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP70158.
    CleanExiMM_SMPDL3A.
    ExpressionAtlasiP70158. baseline and differential.
    GenevisibleiP70158. MM.

    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...

    Publicationsi

    « Hide 'large scale' publications
    1. "Acid sphingomyelinase is a member of a multi-gene family and shares motifs with a large family of metallo-phosphoesterases."
      Hofmann K.
      Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Bone marrow.
    3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas and Spleen.
    6. "Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages."
      Traini M., Quinn C.M., Sandoval C., Johansson E., Schroder K., Kockx M., Meikle P.J., Jessup W., Kritharides L.
      J. Biol. Chem. 289:32895-32913(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    7. Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.
    8. "Structural basis for nucleotide hydrolysis by the acid sphingomyelinase-like phosphodiesterase SMPDL3A."
      Gorelik A., Illes K., Superti-Furga G., Nagar B.
      J. Biol. Chem. 291:6376-6385(2016) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 23-445 IN COMPLEXES WITH ZINC IONS; ATP ANALOG AND PHOSPHOCHOLINE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-111 AND HIS-149, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-66; ASN-128; ASN-235; ASN-353 AND ASN-364, DISULFIDE BONDS.

    Entry informationi

    Entry nameiASM3A_MOUSE
    AccessioniPrimary (citable) accession number: P70158
    Secondary accession number(s): Q3U8C2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 29, 2001
    Last sequence update: July 27, 2011
    Last modified: June 8, 2016
    This is version 100 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.