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Protein

Sphingosine-1-phosphate lyase 1

Gene

SGPL1

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

Functioni

Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis.4 Publications

Catalytic activityi

Sphinganine 1-phosphate = phosphoethanolamine + palmitaldehyde.3 Publications

Cofactori

pyridoxal 5'-phosphate1 Publication

Kineticsi

  1. KM=5.2 µM for sphingosine 1-phosphate1 Publication

    Pathwayi: sphingolipid metabolism

    This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.3 Publications
    View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionLyase
    Biological processApoptosis, Lipid metabolism, Sphingolipid metabolism
    LigandPyridoxal phosphate

    Enzyme and pathway databases

    BRENDAi4.1.2.27 2681
    ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
    UniPathwayi
    UPA00222

    Chemistry databases

    SwissLipidsiSLP:000000107

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sphingosine-1-phosphate lyase 1Curated (EC:4.1.2.273 Publications)
    Short name:
    S1PLCurated
    Short name:
    SP-lyase 1Curated
    Short name:
    SPL 1Curated
    Short name:
    hSPL
    Alternative name(s):
    Sphingosine-1-phosphate aldolase
    Gene namesi
    Name:SGPL1Imported
    Synonyms:KIAA12521 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000166224.16
    HGNCiHGNC:10817 SGPL1
    MIMi603729 gene
    neXtProtiNX_O95470

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 40LumenalSequence analysisAdd BLAST40
    Transmembranei41 – 61Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
    Topological domaini62 – 568CytoplasmicSequence analysisAdd BLAST507

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Nephrotic syndrome 14 (NPHS14)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS14 is an autosomal recessive syndromic, steroid-resistant form that progresses to end-stage renal failure. Some NPHS14 patients manifest ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects.
    See also OMIM:617575
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_079213222R → Q in NPHS14; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 2 PublicationsCorresponds to variant dbSNP:rs769259446EnsemblClinVar.1
    Natural variantiVAR_079214222R → W in NPHS14. 1 PublicationCorresponds to variant dbSNP:rs1131692255Ensembl.1
    Natural variantiVAR_079216416Y → C in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs779485098Ensembl.1
    Natural variantiVAR_079217505 – 568Missing in NPHS14. 1 PublicationAdd BLAST64
    Natural variantiVAR_079218545Missing in NPHS14; decreased protein abundance. 1 Publication1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi132E → G: No effect on the sphinganine-1-phosphate aldolase activity; no effect on protein abundance. 1 Publication1
    Mutagenesisi218C → G: Loss of sphinganine-1-phosphate aldolase activity. 1 Publication1
    Mutagenesisi317C → S: Almost no sphinganine-1-phosphate aldolase activity. 1 Publication1
    Mutagenesisi353K → L: Loss of sphinganine-1-phosphate aldolase activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi8879
    MalaCardsiSGPL1
    MIMi617575 phenotype
    OpenTargetsiENSG00000166224
    PharmGKBiPA35725

    Chemistry databases

    ChEMBLiCHEMBL3286061
    DrugBankiDB00114 Pyridoxal Phosphate
    GuidetoPHARMACOLOGYi2522

    Polymorphism and mutation databases

    BioMutaiSGPL1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001470121 – 568Sphingosine-1-phosphate lyase 1Add BLAST568

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei353N6-(pyridoxal phosphate)lysine; alternate1
    Modified residuei353N6-acetyllysine; alternateCombined sources1
    Modified residuei356Nitrated tyrosineCombined sources1
    Modified residuei366Nitrated tyrosineCombined sources1
    Modified residuei564PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Nitration, Phosphoprotein

    Proteomic databases

    EPDiO95470
    MaxQBiO95470
    PaxDbiO95470
    PeptideAtlasiO95470
    PRIDEiO95470
    ProteomicsDBi50902

    PTM databases

    iPTMnetiO95470
    PhosphoSitePlusiO95470
    SwissPalmiO95470

    Expressioni

    Tissue specificityi

    Ubiquitously expressed (PubMed:11018465, PubMed:28165343). Expressed in fetal and adult adrenal gland (at protein level) (PubMed:28165343).2 Publications

    Gene expression databases

    BgeeiENSG00000166224 Expressed in 217 organ(s), highest expression level in esophagus squamous epithelium
    CleanExiHS_SGPL1
    ExpressionAtlasiO95470 baseline and differential
    GenevisibleiO95470 HS

    Organism-specific databases

    HPAiHPA021125
    HPA023086

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TMEM173Q86WV62EBI-1046170,EBI-2800345

    Protein-protein interaction databases

    BioGridi114398, 54 interactors
    IntActiO95470, 36 interactors
    MINTiO95470
    STRINGi9606.ENSP00000362298

    Chemistry databases

    BindingDBiO95470

    Structurei

    Secondary structure

    1568
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO95470
    SMRiO95470
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1383 Eukaryota
    COG0076 LUCA
    GeneTreeiENSGT00390000000046
    HOGENOMiHOG000190693
    HOVERGENiHBG056982
    InParanoidiO95470
    KOiK01634
    OMAiDPHKMGL
    OrthoDBiEOG091G040L
    PhylomeDBiO95470
    TreeFamiTF300777

    Family and domain databases

    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    InterProiView protein in InterPro
    IPR002129 PyrdxlP-dep_de-COase
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    PfamiView protein in Pfam
    PF00282 Pyridoxal_deC, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    O95470-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MPSTDLLMLK AFEPYLEILE VYSTKAKNYV NGHCTKYEPW QLIAWSVVWT
    60 70 80 90 100
    LLIVWGYEFV FQPESLWSRF KKKCFKLTRK MPIIGRKIQD KLNKTKDDIS
    110 120 130 140 150
    KNMSFLKVDK EYVKALPSQG LSSSAVLEKL KEYSSMDAFW QEGRASGTVY
    160 170 180 190 200
    SGEEKLTELL VKAYGDFAWS NPLHPDIFPG LRKIEAEIVR IACSLFNGGP
    210 220 230 240 250
    DSCGCVTSGG TESILMACKA YRDLAFEKGI KTPEIVAPQS AHAAFNKAAS
    260 270 280 290 300
    YFGMKIVRVP LTKMMEVDVR AMRRAISRNT AMLVCSTPQF PHGVIDPVPE
    310 320 330 340 350
    VAKLAVKYKI PLHVDACLGG FLIVFMEKAG YPLEHPFDFR VKGVTSISAD
    360 370 380 390 400
    THKYGYAPKG SSLVLYSDKK YRNYQFFVDT DWQGGIYASP TIAGSRPGGI
    410 420 430 440 450
    SAACWAALMH FGENGYVEAT KQIIKTARFL KSELENIKGI FVFGNPQLSV
    460 470 480 490 500
    IALGSRDFDI YRLSNLMTAK GWNLNQLQFP PSIHFCITLL HARKRVAIQF
    510 520 530 540 550
    LKDIRESVTQ IMKNPKAKTT GMGAIYGMAQ TTVDRNMVAE LSSVFLDSLY
    560
    STDTVTQGSQ MNGSPKPH
    Length:568
    Mass (Da):63,524
    Last modified:October 24, 2003 - v3
    Checksum:i3B16FDEFC4B2FDB6
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H7BXL7H7BXL7_HUMAN
    Sphingosine-1-phosphate lyase 1
    SGPL1
    202Annotation score:
    H0Y3V8H0Y3V8_HUMAN
    Sphingosine-1-phosphate lyase 1
    SGPL1
    135Annotation score:

    Sequence cautioni

    The sequence BAA86566 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti404C → A in CAA09590 (PubMed:11018465).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04887521V → L. Corresponds to variant dbSNP:rs12770335Ensembl.1
    Natural variantiVAR_079213222R → Q in NPHS14; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 2 PublicationsCorresponds to variant dbSNP:rs769259446EnsemblClinVar.1
    Natural variantiVAR_079214222R → W in NPHS14. 1 PublicationCorresponds to variant dbSNP:rs1131692255Ensembl.1
    Natural variantiVAR_079215346S → I in NPHS1; decreased protein abundance in cells of patients homozygous for the mutation; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 1 PublicationCorresponds to variant dbSNP:rs1131692256Ensembl.1
    Natural variantiVAR_079216416Y → C in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs779485098Ensembl.1
    Natural variantiVAR_079217505 – 568Missing in NPHS14. 1 PublicationAdd BLAST64
    Natural variantiVAR_079218545Missing in NPHS14; decreased protein abundance. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ011304 mRNA Translation: CAA09590.2
    AF144638 mRNA Translation: AAD44755.1
    AB033078 mRNA Translation: BAA86566.1 Different initiation.
    AK314615 mRNA Translation: BAG37181.1
    CH471083 Genomic DNA Translation: EAW54414.1
    BC052991 mRNA Translation: AAH52991.1
    CCDSiCCDS31216.1
    RefSeqiNP_003892.2, NM_003901.3
    XP_005270320.1, XM_005270263.1
    XP_011538618.1, XM_011540316.2
    XP_011538619.1, XM_011540317.1
    UniGeneiHs.499984

    Genome annotation databases

    EnsembliENST00000373202; ENSP00000362298; ENSG00000166224
    GeneIDi8879
    KEGGihsa:8879
    UCSCiuc001jrm.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ011304 mRNA Translation: CAA09590.2
    AF144638 mRNA Translation: AAD44755.1
    AB033078 mRNA Translation: BAA86566.1 Different initiation.
    AK314615 mRNA Translation: BAG37181.1
    CH471083 Genomic DNA Translation: EAW54414.1
    BC052991 mRNA Translation: AAH52991.1
    CCDSiCCDS31216.1
    RefSeqiNP_003892.2, NM_003901.3
    XP_005270320.1, XM_005270263.1
    XP_011538618.1, XM_011540316.2
    XP_011538619.1, XM_011540317.1
    UniGeneiHs.499984

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4Q6RX-ray2.40A/B62-568[»]
    ProteinModelPortaliO95470
    SMRiO95470
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114398, 54 interactors
    IntActiO95470, 36 interactors
    MINTiO95470
    STRINGi9606.ENSP00000362298

    Chemistry databases

    BindingDBiO95470
    ChEMBLiCHEMBL3286061
    DrugBankiDB00114 Pyridoxal Phosphate
    GuidetoPHARMACOLOGYi2522
    SwissLipidsiSLP:000000107

    PTM databases

    iPTMnetiO95470
    PhosphoSitePlusiO95470
    SwissPalmiO95470

    Polymorphism and mutation databases

    BioMutaiSGPL1

    Proteomic databases

    EPDiO95470
    MaxQBiO95470
    PaxDbiO95470
    PeptideAtlasiO95470
    PRIDEiO95470
    ProteomicsDBi50902

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000373202; ENSP00000362298; ENSG00000166224
    GeneIDi8879
    KEGGihsa:8879
    UCSCiuc001jrm.4 human

    Organism-specific databases

    CTDi8879
    DisGeNETi8879
    EuPathDBiHostDB:ENSG00000166224.16
    GeneCardsiSGPL1
    HGNCiHGNC:10817 SGPL1
    HPAiHPA021125
    HPA023086
    MalaCardsiSGPL1
    MIMi603729 gene
    617575 phenotype
    neXtProtiNX_O95470
    OpenTargetsiENSG00000166224
    PharmGKBiPA35725
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1383 Eukaryota
    COG0076 LUCA
    GeneTreeiENSGT00390000000046
    HOGENOMiHOG000190693
    HOVERGENiHBG056982
    InParanoidiO95470
    KOiK01634
    OMAiDPHKMGL
    OrthoDBiEOG091G040L
    PhylomeDBiO95470
    TreeFamiTF300777

    Enzyme and pathway databases

    UniPathwayi
    UPA00222

    BRENDAi4.1.2.27 2681
    ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis

    Miscellaneous databases

    ChiTaRSiSGPL1 human
    GeneWikiiSGPL1
    GenomeRNAii8879
    PROiPR:O95470
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000166224 Expressed in 217 organ(s), highest expression level in esophagus squamous epithelium
    CleanExiHS_SGPL1
    ExpressionAtlasiO95470 baseline and differential
    GenevisibleiO95470 HS

    Family and domain databases

    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    InterProiView protein in InterPro
    IPR002129 PyrdxlP-dep_de-COase
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    PfamiView protein in Pfam
    PF00282 Pyridoxal_deC, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSGPL1_HUMAN
    AccessioniPrimary (citable) accession number: O95470
    Secondary accession number(s): B2RBD4
    , Q7Z732, Q9ULG8, Q9UN89
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2003
    Last sequence update: October 24, 2003
    Last modified: September 12, 2018
    This is version 159 of the entry and version 3 of the sequence. See 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families
    4. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    5. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    6. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    7. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
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