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Protein

Sphingosine kinase 1

Gene

SPHK1

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

Functioni

Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol.2 Publications

Catalytic activityi

ATP + sphinganine = ADP + sphinganine 1-phosphate.
ATP + sphingosine = ADP + sphingosine 1-phosphate.

Cofactori

Mg2+1 Publication

Kineticsi

  1. KM=14 µM for sphingosine1 Publication
  2. KM=20 µM for dihydrosphingosine1 Publication
  3. KM=77 µM for ATP1 Publication

    pH dependencei

    Optimum pH is 7.4.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei81 – 811Proton donor/acceptor1 Publication
    Binding sitei86 – 861ATP
    Binding sitei178 – 1781Substrate
    Binding sitei185 – 1851ATP
    Binding sitei191 – 1911ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi22 – 243ATP
    Nucleotide bindingi54 – 585ATP
    Nucleotide bindingi111 – 1133ATP
    Nucleotide bindingi341 – 3433ATP

    GO - Molecular functioni

    • ATP binding Source: UniProtKB
    • calmodulin binding Source: UniProtKB
    • D-erythro-sphingosine kinase activity Source: UniProtKB
    • DNA binding Source: MGI
    • magnesium ion binding Source: UniProtKB
    • protein phosphatase 2A binding Source: BHF-UCL
    • sphinganine kinase activity Source: MGI
    • sphingosine-1-phosphate receptor activity Source: UniProtKB

    GO - Biological processi

    • 'de novo' posttranslational protein folding Source: Reactome
    • blood vessel development Source: Ensembl
    • brain development Source: Ensembl
    • calcium-mediated signaling Source: UniProtKB
    • cellular protein metabolic process Source: Reactome
    • cellular response to growth factor stimulus Source: Ensembl
    • cellular response to hydrogen peroxide Source: Ensembl
    • cellular response to starvation Source: Ensembl
    • cyclooxygenase pathway Source: Ensembl
    • female pregnancy Source: Ensembl
    • inflammatory response Source: Ensembl
    • intracellular signal transduction Source: UniProtKB
    • lipid phosphorylation Source: GOC
    • negative regulation of apoptotic process Source: UniProtKB
    • positive regulation of angiogenesis Source: UniProtKB
    • positive regulation of cell growth Source: UniProtKB
    • positive regulation of cell migration Source: UniProtKB
    • positive regulation of fibroblast proliferation Source: MGI
    • positive regulation of mitotic cell cycle Source: UniProtKB
    • positive regulation of neuron projection development Source: Ensembl
    • positive regulation of neurotransmitter secretion Source: Ensembl
    • positive regulation of NF-kappaB import into nucleus Source: UniProtKB
    • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    • positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    • positive regulation of protein ubiquitination Source: UniProtKB
    • positive regulation of smooth muscle contraction Source: UniProtKB
    • protein folding Source: Reactome
    • regulation of interleukin-1 beta production Source: Ensembl
    • regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
    • response to amine Source: Ensembl
    • response to ATP Source: Ensembl
    • response to interleukin-1 Source: Ensembl
    • response to magnesium ion Source: Ensembl
    • response to progesterone Source: Ensembl
    • signal transduction Source: ProtInc
    • small molecule metabolic process Source: Reactome
    • sphingoid catabolic process Source: UniProtKB
    • sphingolipid biosynthetic process Source: Reactome
    • sphingolipid metabolic process Source: Reactome
    • sphingosine-1-phosphate signaling pathway Source: GOC
    • sphingosine biosynthetic process Source: UniProtKB
    • sphingosine metabolic process Source: UniProtKB
    • vascular endothelial growth factor receptor signaling pathway Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Calmodulin-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.91. 2681.
    ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.
    REACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
    REACT_264273. VEGFR2 mediated cell proliferation.
    SABIO-RKQ9NYA1.
    SignaLinkiQ9NYA1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sphingosine kinase 1 (EC:2.7.1.91)
    Short name:
    SK 1
    Short name:
    SPK 1
    Gene namesi
    Name:SPHK1
    Synonyms:SPHK, SPK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:11240. SPHK1.

    Subcellular locationi

    GO - Cellular componenti

    • axon Source: Ensembl
    • cytoplasm Source: UniProtKB
    • cytosol Source: UniProtKB
    • nucleus Source: UniProtKB-SubCell
    • plasma membrane Source: UniProtKB
    • synaptic vesicle Source: Ensembl
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi81 – 811D → A: Loss of enzyme activity. 1 Publication
    Mutagenesisi81 – 811D → N: Strongly reduced enzyme activity. 1 Publication
    Mutagenesisi82 – 821G → D: Loss of enzyme activity. 1 Publication
    Mutagenesisi197 – 1971F → A: Abolishes interaction with CIB1; when associated with A-198.
    Mutagenesisi198 – 1981L → A: Abolishes interaction with CIB1; when associated with A-197.

    Organism-specific databases

    PharmGKBiPA36070.

    Chemistry

    DrugBankiDB08868. Fingolimod.

    Polymorphism and mutation databases

    BioMutaiSPHK1.
    DMDMi17369329.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 384384Sphingosine kinase 1PRO_0000181357Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei193 – 1931Phosphothreonine1 Publication
    Modified residuei225 – 2251Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9NYA1.
    PaxDbiQ9NYA1.
    PRIDEiQ9NYA1.

    PTM databases

    PhosphoSiteiQ9NYA1.

    Expressioni

    Tissue specificityi

    Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle.1 Publication

    Gene expression databases

    BgeeiQ9NYA1.
    CleanExiHS_SPHK1.
    ExpressionAtlasiQ9NYA1. baseline and differential.
    GenevisibleiQ9NYA1. HS.

    Organism-specific databases

    HPAiHPA022829.
    HPA028761.

    Interactioni

    Subunit structurei

    Interacts with ACY1 (By similarity). Binds to calmodulin. Interacts with SPHKAP. Interacts with CIB1, the interaction occurs in a calcium-dependent manner.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CTSBP078584EBI-985303,EBI-715062
    EEF1A1P681042EBI-985303,EBI-352162
    FHL2Q141927EBI-985303,EBI-701903
    SPHKAPQ2M3C74EBI-985303,EBI-1803914
    TRAF6Q9Y4K32EBI-985303,EBI-359276

    Protein-protein interaction databases

    BioGridi114396. 12 interactions.
    IntActiQ9NYA1. 7 interactions.
    MINTiMINT-226199.
    STRINGi9606.ENSP00000313681.

    Structurei

    Secondary structure

    1
    384
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi13 – 219Combined sources
    Turni26 – 294Combined sources
    Helixi30 – 378Combined sources
    Helixi39 – 446Combined sources
    Beta strandi47 – 537Combined sources
    Helixi59 – 668Combined sources
    Helixi69 – 713Combined sources
    Beta strandi73 – 808Combined sources
    Helixi81 – 9212Combined sources
    Helixi97 – 1004Combined sources
    Beta strandi105 – 1095Combined sources
    Helixi115 – 1239Combined sources
    Helixi131 – 14414Combined sources
    Beta strandi146 – 15712Combined sources
    Beta strandi162 – 17211Combined sources
    Helixi173 – 1819Combined sources
    Helixi182 – 1909Combined sources
    Helixi191 – 20111Combined sources
    Beta strandi206 – 2149Combined sources
    Helixi215 – 2184Combined sources
    Beta strandi230 – 2323Combined sources
    Beta strandi249 – 2513Combined sources
    Beta strandi255 – 26612Combined sources
    Beta strandi285 – 2917Combined sources
    Helixi296 – 30510Combined sources
    Helixi306 – 3083Combined sources
    Helixi311 – 3144Combined sources
    Beta strandi319 – 33113Combined sources
    Beta strandi333 – 3353Combined sources
    Beta strandi337 – 3404Combined sources
    Beta strandi343 – 3464Combined sources
    Beta strandi350 – 36213Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3VZBX-ray2.00A/B/C9-364[»]
    3VZCX-ray2.30A/B/C/D/E/F9-364[»]
    3VZDX-ray2.30A/B/C/D/E/F9-364[»]
    4L02X-ray2.75A/B/C9-364[»]
    4V24X-ray1.80A/B1-363[»]
    ProteinModelPortaliQ9NYA1.
    SMRiQ9NYA1. Positions 9-364.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini12 – 159148DAGKcPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni79 – 824Substrate binding

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi147 – 1559Nuclear export signal 1
    Motifi161 – 1699Nuclear export signal 2

    Sequence similaritiesi

    Contains 1 DAGKc domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG1597.
    GeneTreeiENSGT00690000101761.
    HOGENOMiHOG000111460.
    HOVERGENiHBG054796.
    InParanoidiQ9NYA1.
    KOiK04718.
    OMAiDCPYLVY.
    PhylomeDBiQ9NYA1.
    TreeFamiTF354296.

    Family and domain databases

    InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
    IPR016064. NAD/diacylglycerol_kinase.
    [Graphical view]
    PfamiPF00781. DAGK_cat. 1 hit.
    [Graphical view]
    SMARTiSM00046. DAGKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF111331. SSF111331. 2 hits.
    PROSITEiPS50146. DAGK. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NYA1-1) [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
    MDPAGGPRGV LPRPCRVLVL LNPRGGKGKA LQLFRSHVQP LLAEAEISFT
    60 70 80 90 100
    LMLTERRNHA RELVRSEELG RWDALVVMSG DGLMHEVVNG LMERPDWETA
    110 120 130 140 150
    IQKPLCSLPA GSGNALAASL NHYAGYEQVT NEDLLTNCTL LLCRRLLSPM
    160 170 180 190 200
    NLLSLHTASG LRLFSVLSLA WGFIADVDLE SEKYRRLGEM RFTLGTFLRL
    210 220 230 240 250
    AALRTYRGRL AYLPVGRVGS KTPASPVVVQ QGPVDAHLVP LEEPVPSHWT
    260 270 280 290 300
    VVPDEDFVLV LALLHSHLGS EMFAAPMGRC AAGVMHLFYV RAGVSRAMLL
    310 320 330 340 350
    RLFLAMEKGR HMEYECPYLV YVPVVAFRLE PKDGKGVFAV DGELMVSEAV
    360 370 380
    QGQVHPNYFW MVSGCVEPPP SWKPQQMPPP EEPL
    Length:384
    Mass (Da):42,518
    Last modified:October 1, 2000 - v1
    Checksum:iEB04A7F2034C2DB0
    GO
    Isoform 2 (identifier: Q9NYA1-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MSAQVLGFLR...WQREPRVEVM

    Show »
    Length:470
    Mass (Da):51,054
    Checksum:iF6BF2D324E12CFC0
    GO
    Isoform 3 (identifier: Q9NYA1-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         3-3: P → PVVGCGRGLFGFVFS

    Show »
    Length:398
    Mass (Da):43,944
    Checksum:i7F2C9B26C030E560
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti6 – 61Missing in CAB92131 (Ref. 4) Curated
    Sequence conflicti11 – 155LPRPC → ARL in CAB92131 (Ref. 4) Curated
    Sequence conflicti114 – 1152NA → KP in CAB92131 (Ref. 4) Curated
    Sequence conflicti251 – 2511V → M in AAF73423 (PubMed:10802064).Curated
    Sequence conflicti260 – 2601V → I in AAF73423 (PubMed:10802064).Curated
    Sequence conflicti302 – 3021L → F in AAF73423 (PubMed:10802064).Curated
    Sequence conflicti325 – 3251V → G in CAB92131 (Ref. 4) Curated
    Sequence conflicti337 – 3371V → M in AAG01980 (PubMed:10947957).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Isoform 2 (identifier: Q9NYA1-2)
    Natural varianti34 – 341A → T.
    Corresponds to variant rs346803 [ dbSNP | Ensembl ].

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MSAQVLGFLRSWTPLPLAAP RGPAAAGNDAGAPAATAPGG EGEPHSRPCDARLGSTDKEL KAGAAATGSAPTAPGTPWQR EPRVEVM in isoform 2. 2 PublicationsVSP_035453
    Alternative sequencei3 – 31P → PVVGCGRGLFGFVFS in isoform 3. 1 PublicationVSP_047078

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF266756 mRNA. Translation: AAF73470.1.
    AF238083 mRNA. Translation: AAF73423.1.
    AF200328 mRNA. Translation: AAG01980.1.
    AK023393 mRNA. Translation: BAB14558.1.
    AK292294 mRNA. Translation: BAF84983.1.
    AK022402 mRNA. Translation: BAB14028.1.
    AJ245504 mRNA. Translation: CAB92131.1.
    AC090699 Genomic DNA. No translation available.
    CH471099 Genomic DNA. Translation: EAW89392.1.
    CH471099 Genomic DNA. Translation: EAW89393.1.
    BC009419 mRNA. Translation: AAH09419.1.
    BC014439 mRNA. Translation: AAH14439.1.
    BC030553 mRNA. Translation: AAH30553.1.
    CCDSiCCDS11744.1. [Q9NYA1-2]
    CCDS45785.1. [Q9NYA1-1]
    CCDS59297.1. [Q9NYA1-3]
    RefSeqiNP_001136073.1. NM_001142601.1. [Q9NYA1-1]
    NP_001136074.1. NM_001142602.1. [Q9NYA1-1]
    NP_068807.2. NM_021972.3. [Q9NYA1-3]
    NP_892010.2. NM_182965.2. [Q9NYA1-2]
    XP_005257823.1. XM_005257766.2. [Q9NYA1-1]
    UniGeneiHs.68061.

    Genome annotation databases

    EnsembliENST00000323374; ENSP00000313681; ENSG00000176170. [Q9NYA1-2]
    ENST00000392496; ENSP00000376285; ENSG00000176170. [Q9NYA1-1]
    ENST00000545180; ENSP00000440970; ENSG00000176170. [Q9NYA1-1]
    ENST00000590959; ENSP00000468547; ENSG00000176170. [Q9NYA1-3]
    ENST00000592299; ENSP00000465726; ENSG00000176170. [Q9NYA1-1]
    GeneIDi8877.
    KEGGihsa:8877.
    UCSCiuc002jrf.1. human. [Q9NYA1-1]
    uc002jrh.2. human.
    uc002jrj.2. human. [Q9NYA1-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF266756 mRNA. Translation: AAF73470.1.
    AF238083 mRNA. Translation: AAF73423.1.
    AF200328 mRNA. Translation: AAG01980.1.
    AK023393 mRNA. Translation: BAB14558.1.
    AK292294 mRNA. Translation: BAF84983.1.
    AK022402 mRNA. Translation: BAB14028.1.
    AJ245504 mRNA. Translation: CAB92131.1.
    AC090699 Genomic DNA. No translation available.
    CH471099 Genomic DNA. Translation: EAW89392.1.
    CH471099 Genomic DNA. Translation: EAW89393.1.
    BC009419 mRNA. Translation: AAH09419.1.
    BC014439 mRNA. Translation: AAH14439.1.
    BC030553 mRNA. Translation: AAH30553.1.
    CCDSiCCDS11744.1. [Q9NYA1-2]
    CCDS45785.1. [Q9NYA1-1]
    CCDS59297.1. [Q9NYA1-3]
    RefSeqiNP_001136073.1. NM_001142601.1. [Q9NYA1-1]
    NP_001136074.1. NM_001142602.1. [Q9NYA1-1]
    NP_068807.2. NM_021972.3. [Q9NYA1-3]
    NP_892010.2. NM_182965.2. [Q9NYA1-2]
    XP_005257823.1. XM_005257766.2. [Q9NYA1-1]
    UniGeneiHs.68061.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3VZBX-ray2.00A/B/C9-364[»]
    3VZCX-ray2.30A/B/C/D/E/F9-364[»]
    3VZDX-ray2.30A/B/C/D/E/F9-364[»]
    4L02X-ray2.75A/B/C9-364[»]
    4V24X-ray1.80A/B1-363[»]
    ProteinModelPortaliQ9NYA1.
    SMRiQ9NYA1. Positions 9-364.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114396. 12 interactions.
    IntActiQ9NYA1. 7 interactions.
    MINTiMINT-226199.
    STRINGi9606.ENSP00000313681.

    Chemistry

    BindingDBiQ9NYA1.
    ChEMBLiCHEMBL4394.
    DrugBankiDB08868. Fingolimod.
    GuidetoPHARMACOLOGYi2204.

    PTM databases

    PhosphoSiteiQ9NYA1.

    Polymorphism and mutation databases

    BioMutaiSPHK1.
    DMDMi17369329.

    Proteomic databases

    MaxQBiQ9NYA1.
    PaxDbiQ9NYA1.
    PRIDEiQ9NYA1.

    Protocols and materials databases

    DNASUi8877.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000323374; ENSP00000313681; ENSG00000176170. [Q9NYA1-2]
    ENST00000392496; ENSP00000376285; ENSG00000176170. [Q9NYA1-1]
    ENST00000545180; ENSP00000440970; ENSG00000176170. [Q9NYA1-1]
    ENST00000590959; ENSP00000468547; ENSG00000176170. [Q9NYA1-3]
    ENST00000592299; ENSP00000465726; ENSG00000176170. [Q9NYA1-1]
    GeneIDi8877.
    KEGGihsa:8877.
    UCSCiuc002jrf.1. human. [Q9NYA1-1]
    uc002jrh.2. human.
    uc002jrj.2. human. [Q9NYA1-2]

    Organism-specific databases

    CTDi8877.
    GeneCardsiGC17P074380.
    HGNCiHGNC:11240. SPHK1.
    HPAiHPA022829.
    HPA028761.
    MIMi603730. gene.
    neXtProtiNX_Q9NYA1.
    PharmGKBiPA36070.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG1597.
    GeneTreeiENSGT00690000101761.
    HOGENOMiHOG000111460.
    HOVERGENiHBG054796.
    InParanoidiQ9NYA1.
    KOiK04718.
    OMAiDCPYLVY.
    PhylomeDBiQ9NYA1.
    TreeFamiTF354296.

    Enzyme and pathway databases

    BRENDAi2.7.1.91. 2681.
    ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.
    REACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
    REACT_264273. VEGFR2 mediated cell proliferation.
    SABIO-RKQ9NYA1.
    SignaLinkiQ9NYA1.

    Miscellaneous databases

    ChiTaRSiSPHK1. human.
    GeneWikiiSphingosine_kinase_1.
    GenomeRNAii8877.
    NextBioi33329.
    PROiQ9NYA1.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9NYA1.
    CleanExiHS_SPHK1.
    ExpressionAtlasiQ9NYA1. baseline and differential.
    GenevisibleiQ9NYA1. HS.

    Family and domain databases

    InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
    IPR016064. NAD/diacylglycerol_kinase.
    [Graphical view]
    PfamiPF00781. DAGK_cat. 1 hit.
    [Graphical view]
    SMARTiSM00046. DAGKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF111331. SSF111331. 2 hits.
    PROSITEiPS50146. DAGK. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution."
      Melendez A.J., Carlos-Dias E., Gosink M., Allen J.M., Takacs L.
      Gene 251:19-26(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, TISSUE SPECIFICITY.
    3. "Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes."
      Pitson S.M., D'Andrea R.J., Vandeleur L., Moretti P.A.B., Xia P., Gamble J.R., Vadas M.A., Wattenberg B.W.
      Biochem. J. 350:429-441(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
    4. Van Veldhoven P.P., Gijsbers S.
      Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Mammary gland, Ovary and Testis.
    6. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "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] (ISOFORMS 2 AND 3).
      Tissue: Blood, Kidney and Skin.
    9. "Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity."
      Lacana E., Maceyka M., Milstien S., Spiegel S.
      J. Biol. Chem. 277:32947-32953(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPHKAP.
    10. "Identification of functional nuclear export sequences in human sphingosine kinase 1."
      Inagaki Y., Li P.Y., Wada A., Mitsutake S., Igarashi Y.
      Biochem. Biophys. Res. Commun. 311:168-173(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNALS.
    11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. "Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1."
      Jarman K.E., Moretti P.A., Zebol J.R., Pitson S.M.
      J. Biol. Chem. 285:483-492(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CIB1, SUBCELLULAR LOCATION, MUTAGENESIS OF 197-PHE-LEU-198.
    13. "Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2."
      Alvarez S.E., Harikumar K.B., Hait N.C., Allegood J., Strub G.M., Kim E.Y., Maceyka M., Jiang H., Luo C., Kordula T., Milstien S., Spiegel S.
      Nature 465:1084-1088(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLY-82, PHOSPHORYLATION AT SER-225.
    14. "Molecular basis of sphingosine kinase 1 substrate recognition and catalysis."
      Wang Z., Min X., Xiao S.H., Johnstone S., Romanow W., Meininger D., Xu H., Liu J., Dai J., An S., Thibault S., Walker N.
      Structure 21:798-809(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-364 IN COMPLEXES WITH SUBSTRATE ANALOGS AND ADP, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, MUTAGENESIS OF ASP-81.

    Entry informationi

    Entry nameiSPHK1_HUMAN
    AccessioniPrimary (citable) accession number: Q9NYA1
    Secondary accession number(s): Q8N632
    , Q96GK1, Q9HD92, Q9NY70, Q9NYL3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 24, 2001
    Last sequence update: October 1, 2000
    Last modified: June 24, 2015
    This is version 136 of the entry and version 1 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

    Miscellaneous

    Sphingosine 1-phosphate stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.