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Protein

Sphingosine kinase 2

Gene

SPHK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides.1 Publication

Catalytic activityi

ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate.1 Publication

Cofactori

Mg2+By similarity

Activity regulationi

Inhibited by sulfatide.1 Publication

Kineticsi

  1. KM=3.4 µM for sphingosine1 Publication

    pH dependencei

    Optimum pH is 7.5.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei247Proton donor/acceptorBy similarity1
    Binding sitei252ATPPROSITE-ProRule annotation1
    Binding sitei344SubstrateBy similarity1
    Binding sitei351ATPPROSITE-ProRule annotation1
    Binding sitei357ATPPROSITE-ProRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi188 – 190ATPPROSITE-ProRule annotation3
    Nucleotide bindingi220 – 224ATPPROSITE-ProRule annotation5
    Nucleotide bindingi277 – 279ATPPROSITE-ProRule annotation3
    Nucleotide bindingi622 – 624ATPPROSITE-ProRule annotation3

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • D-erythro-sphingosine kinase activity Source: Reactome
    • NAD+ kinase activity Source: InterPro
    • Ras GTPase binding Source: UniProtKB
    • sphinganine kinase activity Source: Reactome
    • sphingosine-1-phosphate receptor activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Transferase
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.91 2681
    ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
    SIGNORiQ9NRA0

    Chemistry databases

    SwissLipidsiSLP:000000112

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sphingosine kinase 2 (EC:2.7.1.911 Publication)
    Short name:
    SK 2
    Short name:
    SPK 2
    Gene namesi
    Name:SPHK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000063176.15
    HGNCiHGNC:18859 SPHK2
    MIMi607092 gene
    neXtProtiNX_Q9NRA0

    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

    Keywords - Cellular componenti

    Cytoplasm, Lysosome, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi56848
    OpenTargetsiENSG00000063176
    PharmGKBiPA38719

    Chemistry databases

    ChEMBLiCHEMBL3023
    GuidetoPHARMACOLOGYi2205

    Polymorphism and mutation databases

    BioMutaiSPHK2
    DMDMi22001996

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001813581 – 654Sphingosine kinase 2Add BLAST654

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei387PhosphoserineCombined sources1
    Modified residuei393PhosphoserineBy similarity1
    Modified residuei399PhosphoserineCombined sources1
    Modified residuei477PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ9NRA0
    MaxQBiQ9NRA0
    PaxDbiQ9NRA0
    PeptideAtlasiQ9NRA0
    PRIDEiQ9NRA0
    ProteomicsDBi82315
    82316 [Q9NRA0-2]
    82317 [Q9NRA0-3]

    PTM databases

    iPTMnetiQ9NRA0
    PhosphoSitePlusiQ9NRA0

    Expressioni

    Gene expression databases

    BgeeiENSG00000063176 Expressed in 160 organ(s), highest expression level in substantia nigra
    ExpressionAtlasiQ9NRA0 baseline and differential
    GenevisibleiQ9NRA0 HS

    Organism-specific databases

    HPAiHPA065508

    Interactioni

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi121208, 3 interactors
    IntActiQ9NRA0, 5 interactors
    STRINGi9606.ENSP00000245222

    Chemistry databases

    BindingDBiQ9NRA0

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NRA0
    SMRiQ9NRA0
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini178 – 325DAGKcPROSITE-ProRule annotationAdd BLAST148

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 175Required for binding to sulfatide and phosphoinositides and for membrane localizationAdd BLAST175
    Regioni245 – 248Substrate bindingBy similarity4

    Phylogenomic databases

    eggNOGiKOG1116 Eukaryota
    COG1597 LUCA
    GeneTreeiENSGT00690000101761
    HOGENOMiHOG000111460
    HOVERGENiHBG054796
    InParanoidiQ9NRA0
    KOiK04718
    PhylomeDBiQ9NRA0
    TreeFamiTF354296

    Family and domain databases

    Gene3Di3.40.50.10330, 1 hit
    InterProiView protein in InterPro
    IPR017438 ATP-NAD_kinase_N
    IPR001206 Diacylglycerol_kinase_cat_dom
    IPR016064 NAD/diacylglycerol_kinase_sf
    PfamiView protein in Pfam
    PF00781 DAGK_cat, 1 hit
    SMARTiView protein in SMART
    SM00046 DAGKc, 1 hit
    SUPFAMiSSF111331 SSF111331, 1 hit
    PROSITEiView protein in PROSITE
    PS50146 DAGK, 1 hit

    Sequences (5+)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket
    Note: Experimental confirmation may be lacking for some isoforms.

    This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q9NRA0-1) [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
    MNGHLEAEEQ QDQRPDQELT GSWGHGPRST LVRAKAMAPP PPPLAASTPL
    60 70 80 90 100
    LHGEFGSYPA RGPRFALTLT SQALHIQRLR PKPEARPRGG LVPLAEVSGC
    110 120 130 140 150
    CTLRSRSPSD SAAYFCIYTY PRGRRGARRR ATRTFRADGA ATYEENRAEA
    160 170 180 190 200
    QRWATALTCL LRGLPLPGDG EITPDLLPRP PRLLLLVNPF GGRGLAWQWC
    210 220 230 240 250
    KNHVLPMISE AGLSFNLIQT ERQNHARELV QGLSLSEWDG IVTVSGDGLL
    260 270 280 290 300
    HEVLNGLLDR PDWEEAVKMP VGILPCGSGN ALAGAVNQHG GFEPALGLDL
    310 320 330 340 350
    LLNCSLLLCR GGGHPLDLLS VTLASGSRCF SFLSVAWGFV SDVDIQSERF
    360 370 380 390 400
    RALGSARFTL GTVLGLATLH TYRGRLSYLP ATVEPASPTP AHSLPRAKSE
    410 420 430 440 450
    LTLTPDPAPP MAHSPLHRSV SDLPLPLPQP ALASPGSPEP LPILSLNGGG
    460 470 480 490 500
    PELAGDWGGA GDAPLSPDPL LSSPPGSPKA ALHSPVSEGA PVIPPSSGLP
    510 520 530 540 550
    LPTPDARVGA STCGPPDHLL PPLGTPLPPD WVTLEGDFVL MLAISPSHLG
    560 570 580 590 600
    ADLVAAPHAR FDDGLVHLCW VRSGISRAAL LRLFLAMERG SHFSLGCPQL
    610 620 630 640 650
    GYAAARAFRL EPLTPRGVLT VDGEQVEYGP LQAQMHPGIG TLLTGPPGCP

    GREP
    Length:654
    Mass (Da):69,217
    Last modified:July 26, 2002 - v2
    Checksum:iF73FFCEC930DA50F
    GO
    Isoform 2 (identifier: Q9NRA0-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-36: Missing.

    Show »
    Length:618
    Mass (Da):65,205
    Checksum:i1A5B06BCB6F93F1F
    GO
    Isoform 3 (identifier: Q9NRA0-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-36: Missing.
         292-390: FEPALGLDLL...ATVEPASPTP → PREDSDSSTS...NVFICKKKKK

    Show »
    Length:618
    Mass (Da):65,170
    Checksum:iD934F61C0A69EDAE
    GO
    Isoform 4 (identifier: Q9NRA0-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         13-71: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:595
    Mass (Da):62,986
    Checksum:iC24AC949EEEA059B
    GO
    Isoform 5 (identifier: Q9NRA0-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-12: MNGHLEAEEQQD → MIGCLHARVS...NSHPFSPPFP
         640-654: GTLLTGPPGCPGREP → ARGRTQTPALPAAPALYGRQPGAAHGLQPVCQGAALFFHNSWLWGSQDLFRIVLTEAVGG

    Show »
    Length:761
    Mass (Da):80,205
    Checksum:iA52BF3441102A3D3
    GO

    Computationally mapped potential isoform sequencesi

    There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    M0R344M0R344_HUMAN
    Sphingosine kinase 2
    SPHK2
    663Annotation score:
    M0R0E9M0R0E9_HUMAN
    Sphingosine kinase 2
    SPHK2
    255Annotation score:
    E9PCV4E9PCV4_HUMAN
    Sphingosine kinase 2, isoform CRA_e
    SPHK2 hCG_15274
    448Annotation score:
    A0A075B7A1A0A075B7A1_HUMAN
    Sphingosine kinase 2
    SPHK2
    349Annotation score:
    M0QZP3M0QZP3_HUMAN
    Sphingosine kinase 2
    SPHK2
    72Annotation score:
    M0QXX5M0QXX5_HUMAN
    Sphingosine kinase 2
    SPHK2
    133Annotation score:
    E7ET12E7ET12_HUMAN
    Sphingosine kinase 2
    SPHK2
    49Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti49P → S in CAB66636 (PubMed:11230166).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_060112652R → Q. Corresponds to variant dbSNP:rs11881285Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0062171 – 36Missing in isoform 2 and isoform 3. 4 PublicationsAdd BLAST36
    Alternative sequenceiVSP_0477211 – 12MNGHL…EEQQD → MIGCLHARVSGPLWDAGLCP ASSRSAHTCLSLSVSDAPVS PATAPHCLLLSTAPAPPCPC HGVLNSHPFSPPFP in isoform 5. 1 PublicationAdd BLAST12
    Alternative sequenceiVSP_04691013 – 71Missing in isoform 4. 1 PublicationAdd BLAST59
    Alternative sequenceiVSP_006218292 – 390FEPAL…ASPTP → PREDSDSSTSSSACPLWTTA RSCPRAAASMPGSCPLLPQQ LALGFSRFIQDRVNGGGGRI GSLTCRGHTQRTLPAPAREG GGSLFLKNINVFICKKKKK in isoform 3. 1 PublicationAdd BLAST99
    Alternative sequenceiVSP_047722640 – 654GTLLT…PGREP → ARGRTQTPALPAAPALYGRQ PGAAHGLQPVCQGAALFFHN SWLWGSQDLFRIVLTEAVGG in isoform 5. 1 PublicationAdd BLAST15

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF245447 mRNA Translation: AAF74124.1
    EF107108 mRNA Translation: ABK81123.1
    AL136701 mRNA Translation: CAB66636.1
    AK000599 mRNA Translation: BAA91280.1
    AK300541 mRNA Translation: BAG62249.1
    AC022154 Genomic DNA No translation available.
    BC006161 mRNA Translation: AAH06161.1
    BC010671 mRNA Translation: AAH10671.1
    CCDSiCCDS12727.1 [Q9NRA0-1]
    CCDS59404.1 [Q9NRA0-4]
    CCDS59405.1 [Q9NRA0-2]
    RefSeqiNP_001191087.1, NM_001204158.2 [Q9NRA0-4]
    NP_001191088.1, NM_001204159.2 [Q9NRA0-1]
    NP_001191089.1, NM_001204160.2 [Q9NRA0-2]
    NP_064511.2, NM_020126.4 [Q9NRA0-1]
    XP_006723355.1, XM_006723292.1 [Q9NRA0-2]
    XP_011525435.1, XM_011527133.1 [Q9NRA0-1]
    XP_011525436.1, XM_011527134.1 [Q9NRA0-2]
    UniGeneiHs.528006

    Genome annotation databases

    EnsembliENST00000245222; ENSP00000245222; ENSG00000063176 [Q9NRA0-1]
    ENST00000598088; ENSP00000469158; ENSG00000063176 [Q9NRA0-1]
    ENST00000599748; ENSP00000471205; ENSG00000063176 [Q9NRA0-2]
    ENST00000600537; ENSP00000470092; ENSG00000063176 [Q9NRA0-4]
    GeneIDi56848
    KEGGihsa:56848
    UCSCiuc002pjr.4 human [Q9NRA0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF245447 mRNA Translation: AAF74124.1
    EF107108 mRNA Translation: ABK81123.1
    AL136701 mRNA Translation: CAB66636.1
    AK000599 mRNA Translation: BAA91280.1
    AK300541 mRNA Translation: BAG62249.1
    AC022154 Genomic DNA No translation available.
    BC006161 mRNA Translation: AAH06161.1
    BC010671 mRNA Translation: AAH10671.1
    CCDSiCCDS12727.1 [Q9NRA0-1]
    CCDS59404.1 [Q9NRA0-4]
    CCDS59405.1 [Q9NRA0-2]
    RefSeqiNP_001191087.1, NM_001204158.2 [Q9NRA0-4]
    NP_001191088.1, NM_001204159.2 [Q9NRA0-1]
    NP_001191089.1, NM_001204160.2 [Q9NRA0-2]
    NP_064511.2, NM_020126.4 [Q9NRA0-1]
    XP_006723355.1, XM_006723292.1 [Q9NRA0-2]
    XP_011525435.1, XM_011527133.1 [Q9NRA0-1]
    XP_011525436.1, XM_011527134.1 [Q9NRA0-2]
    UniGeneiHs.528006

    3D structure databases

    ProteinModelPortaliQ9NRA0
    SMRiQ9NRA0
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi121208, 3 interactors
    IntActiQ9NRA0, 5 interactors
    STRINGi9606.ENSP00000245222

    Chemistry databases

    BindingDBiQ9NRA0
    ChEMBLiCHEMBL3023
    GuidetoPHARMACOLOGYi2205
    SwissLipidsiSLP:000000112

    PTM databases

    iPTMnetiQ9NRA0
    PhosphoSitePlusiQ9NRA0

    Polymorphism and mutation databases

    BioMutaiSPHK2
    DMDMi22001996

    Proteomic databases

    EPDiQ9NRA0
    MaxQBiQ9NRA0
    PaxDbiQ9NRA0
    PeptideAtlasiQ9NRA0
    PRIDEiQ9NRA0
    ProteomicsDBi82315
    82316 [Q9NRA0-2]
    82317 [Q9NRA0-3]

    Protocols and materials databases

    DNASUi56848
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000245222; ENSP00000245222; ENSG00000063176 [Q9NRA0-1]
    ENST00000598088; ENSP00000469158; ENSG00000063176 [Q9NRA0-1]
    ENST00000599748; ENSP00000471205; ENSG00000063176 [Q9NRA0-2]
    ENST00000600537; ENSP00000470092; ENSG00000063176 [Q9NRA0-4]
    GeneIDi56848
    KEGGihsa:56848
    UCSCiuc002pjr.4 human [Q9NRA0-1]

    Organism-specific databases

    CTDi56848
    DisGeNETi56848
    EuPathDBiHostDB:ENSG00000063176.15
    GeneCardsiSPHK2
    HGNCiHGNC:18859 SPHK2
    HPAiHPA065508
    MIMi607092 gene
    neXtProtiNX_Q9NRA0
    OpenTargetsiENSG00000063176
    PharmGKBiPA38719
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1116 Eukaryota
    COG1597 LUCA
    GeneTreeiENSGT00690000101761
    HOGENOMiHOG000111460
    HOVERGENiHBG054796
    InParanoidiQ9NRA0
    KOiK04718
    PhylomeDBiQ9NRA0
    TreeFamiTF354296

    Enzyme and pathway databases

    BRENDAi2.7.1.91 2681
    ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
    SIGNORiQ9NRA0

    Miscellaneous databases

    ChiTaRSiSPHK2 human
    GeneWikiiSPHK2
    GenomeRNAii56848
    PROiPR:Q9NRA0
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000063176 Expressed in 160 organ(s), highest expression level in substantia nigra
    ExpressionAtlasiQ9NRA0 baseline and differential
    GenevisibleiQ9NRA0 HS

    Family and domain databases

    Gene3Di3.40.50.10330, 1 hit
    InterProiView protein in InterPro
    IPR017438 ATP-NAD_kinase_N
    IPR001206 Diacylglycerol_kinase_cat_dom
    IPR016064 NAD/diacylglycerol_kinase_sf
    PfamiView protein in Pfam
    PF00781 DAGK_cat, 1 hit
    SMARTiView protein in SMART
    SM00046 DAGKc, 1 hit
    SUPFAMiSSF111331 SSF111331, 1 hit
    PROSITEiView protein in PROSITE
    PS50146 DAGK, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSPHK2_HUMAN
    AccessioniPrimary (citable) accession number: Q9NRA0
    Secondary accession number(s): A0T4C8
    , B4DU87, Q9BRN1, Q9H0Q2, Q9NWU7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2001
    Last sequence update: July 26, 2002
    Last modified: November 7, 2018
    This is version 159 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

    1. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    2. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
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