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UniProtKB - Q9NRA0 (SPHK2_HUMAN)

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Protein

Sphingosine kinase 2

Gene

SPHK2

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-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

Enzyme 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
    Complete GO annotation...

    GO - Biological processi

    • blood vessel development Source: Ensembl
    • brain development Source: Ensembl
    • cell proliferation Source: UniProtKB
    • female pregnancy Source: Ensembl
    • negative regulation of apoptotic process Source: UniProtKB
    • positive regulation of cell proliferation Source: Ensembl
    • sphinganine-1-phosphate biosynthetic process Source: UniProtKB
    • sphingolipid biosynthetic process Source: Reactome
    • sphingosine biosynthetic process Source: UniProtKB
    Complete GO annotation...

    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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:18859. SPHK2.

    Subcellular locationi

    Isoform 1 :
    Isoform 2 :

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • intracellular membrane-bounded organelle Source: HPA
    • lysosomal membrane Source: UniProtKB
    • membrane Source: UniProtKB
    Complete GO annotation...

    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.

    PTM databases

    iPTMnetiQ9NRA0.
    PhosphoSitePlusiQ9NRA0.

    Expressioni

    Gene expression databases

    BgeeiENSG00000063176.
    ExpressionAtlasiQ9NRA0. baseline and differential.
    GenevisibleiQ9NRA0. HS.

    Organism-specific databases

    HPAiHPA065508.

    Interactioni

    GO - Molecular functioni

    • Ras GTPase binding Source: UniProtKB
    Complete GO annotation...

    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_dom_1.
    IPR001206. Diacylglycerol_kinase_cat_dom.
    IPR016064. NAD/diacylglycerol_kinase.
    PfamiView protein in Pfam
    PF00781. DAGK_cat. 1 hit.
    SMARTiView protein in SMART
    SM00046. DAGKc. 1 hit.
    SUPFAMiSSF111331. SSF111331. 2 hits.
    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.
    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

    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

    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.

    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: July 5, 2017
    This is version 153 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 chromosome 19
      Human chromosome 19: 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