Human Gene SPHK1 (ENST00000592299.5) Description and Page Index
  Description: Homo sapiens sphingosine kinase 1 (SPHK1), transcript variant 3, mRNA. (from RefSeq NM_001142601)
RefSeq Summary (NM_001142601): The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017].
Gencode Transcript: ENST00000592299.5
Gencode Gene: ENSG00000176170.13
Transcript (Including UTRs)
   Position: hg38 chr17:76,384,609-76,387,860 Size: 3,252 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg38 chr17:76,385,645-76,387,586 Size: 1,942 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:76,384,609-76,387,860)mRNA (may differ from genome)Protein (384 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SPHK1_HUMAN
DESCRIPTION: RecName: Full=Sphingosine kinase 1; Short=SK 1; Short=SPK 1; EC=2.7.1.91;
FUNCTION: 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.
CATALYTIC ACTIVITY: ATP + sphinganine = ADP + sphinganine 1- phosphate.
CATALYTIC ACTIVITY: ATP + sphingosine = ADP + sphingosine 1- phosphate.
COFACTOR: Magnesium.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=14 uM for sphingosine; KM=20 uM for dihydrosphingosine; KM=77 uM for ATP; pH dependence: Optimum pH is 7.4;
SUBUNIT: Interacts with ACY1 (By similarity). Binds to calmodulin. Interacts with SPHKAP.
INTERACTION: P68104:EEF1A1; NbExp=2; IntAct=EBI-985303, EBI-352162; Q14192:FHL2; NbExp=7; IntAct=EBI-985303, EBI-701903; Q2M3C7:SPHKAP; NbExp=4; IntAct=EBI-985303, EBI-1803914;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
TISSUE SPECIFICITY: Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle.
MISCELLANEOUS: Sphingosine 1-phosphate stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling.
SIMILARITY: Contains 1 DAGKc domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: SPHK1
Diseases sorted by gene-association score: renal fibrosis (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 20.13 RPKM in Nerve - Tibial
Total median expression: 196.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -204.60392-0.522 Picture PostScript Text
3' UTR -105.20274-0.384 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001206 - Diacylglycerol_kinase_cat_dom

Pfam Domains:
PF00781 - Diacylglycerol kinase catalytic domain

ModBase Predicted Comparative 3D Structure on Q9NYA1
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0003677 DNA binding
GO:0003951 NAD+ kinase activity
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005524 ATP binding
GO:0008481 sphinganine kinase activity
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0017050 D-erythro-sphingosine kinase activity
GO:0038036 sphingosine-1-phosphate receptor activity
GO:0051721 protein phosphatase 2A binding

Biological Process:
GO:0001568 blood vessel development
GO:0003376 sphingosine-1-phosphate signaling pathway
GO:0006457 protein folding
GO:0006670 sphingosine metabolic process
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007420 brain development
GO:0008152 metabolic process
GO:0008284 positive regulation of cell proliferation
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0016310 phosphorylation
GO:0019722 calcium-mediated signaling
GO:0030148 sphingolipid biosynthetic process
GO:0030307 positive regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0031398 positive regulation of protein ubiquitination
GO:0032651 regulation of interleukin-1 beta production
GO:0035556 intracellular signal transduction
GO:0043066 negative regulation of apoptotic process
GO:0045766 positive regulation of angiogenesis
GO:0045931 positive regulation of mitotic cell cycle
GO:0045987 positive regulation of smooth muscle contraction
GO:0046512 sphingosine biosynthetic process
GO:0046521 sphingoid catabolic process
GO:0046834 lipid phosphorylation
GO:0048146 positive regulation of fibroblast proliferation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:1901224 positive regulation of NIK/NF-kappaB signaling

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  AK122781 - Homo sapiens cDNA FLJ16332 fis, clone SYNOV2016837, highly similar to Sphingosine kinase 1 (EC 2.7.1.-).
AK095578 - Homo sapiens cDNA FLJ38259 fis, clone FCBBF3001302, highly similar to Homo sapiens sphingosine kinase (SPHK1) mRNA.
AK022402 - Homo sapiens cDNA FLJ12340 fis, clone MAMMA1002268, moderately similar to Mus musculus sphingosine kinase (SPHK1a) mRNA.
BC009419 - Homo sapiens sphingosine kinase 1, mRNA (cDNA clone MGC:15040 IMAGE:3506924), complete cds.
AK225250 - Homo sapiens mRNA for sphingosine kinase 1 isoform 2 variant, clone: DMC02610.
AK225258 - Homo sapiens mRNA for sphingosine kinase 1 isoform 1 variant, clone: DMC03040.
BC030553 - Homo sapiens sphingosine kinase 1, mRNA (cDNA clone MGC:40267 IMAGE:5213270), complete cds.
AF238083 - Homo sapiens sphingosine kinase-1 mRNA, complete cds.
BC014439 - Homo sapiens sphingosine kinase 1, mRNA (cDNA clone MGC:22956 IMAGE:4871343), complete cds.
BC008040 - Homo sapiens sphingosine kinase 1, mRNA (cDNA clone MGC:15041 IMAGE:3831657), complete cds.
JD461987 - Sequence 443011 from Patent EP1572962.
AK292294 - Homo sapiens cDNA FLJ77593 complete cds, highly similar to Homo sapiens sphingosine kinase 1 (SPHK1), transcript variant 2, mRNA.
CU688902 - Synthetic construct Homo sapiens gateway clone IMAGE:100023222 5' read SPHK1 mRNA.
CU676993 - Synthetic construct Homo sapiens gateway clone IMAGE:100021981 5' read SPHK1 mRNA.
KJ897925 - Synthetic construct Homo sapiens clone ccsbBroadEn_07319 SPHK1 gene, encodes complete protein.
AK292614 - Homo sapiens cDNA FLJ78254 complete cds.
AK023393 - Homo sapiens cDNA FLJ13331 fis, clone OVARC1001809, moderately similar to Mus musculus sphingosine kinase (SPHK1a) mRNA.
AF266756 - Homo sapiens sphingosine kinase (SPHK1) mRNA, complete cds.
JD231092 - Sequence 212116 from Patent EP1572962.
JD139323 - Sequence 120347 from Patent EP1572962.
JD444356 - Sequence 425380 from Patent EP1572962.
AF200328 - Homo sapiens sphingosine kinase (SPHK) mRNA, complete cds.
CU679355 - Synthetic construct Homo sapiens gateway clone IMAGE:100017184 5' read SPHK1 mRNA.
KJ905363 - Synthetic construct Homo sapiens clone ccsbBroadEn_14918 SPHK1 gene, encodes complete protein.
KJ897924 - Synthetic construct Homo sapiens clone ccsbBroadEn_07318 SPHK1 gene, encodes complete protein.
CU675907 - Synthetic construct Homo sapiens gateway clone IMAGE:100019184 5' read SPHK1 mRNA.
AJ245504 - Homo sapiens mRNA for sphingosine kinase (gene SPK).
BC004112 - Homo sapiens sphingosine kinase 1, mRNA (cDNA clone IMAGE:3832587), partial cds.
JD382037 - Sequence 363061 from Patent EP1572962.
JD258596 - Sequence 239620 from Patent EP1572962.
JD535143 - Sequence 516167 from Patent EP1572962.
JD330111 - Sequence 311135 from Patent EP1572962.
JD255930 - Sequence 236954 from Patent EP1572962.
JD514847 - Sequence 495871 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00600 - Sphingolipid metabolism
hsa01100 - Metabolic pathways
hsa04020 - Calcium signaling pathway
hsa04370 - VEGF signaling pathway
hsa04666 - Fc gamma R-mediated phagocytosis

BioCarta from NCI Cancer Genome Anatomy Project
h_edg1Pathway - Phospholipids as signalling intermediaries

Reactome (by CSHL, EBI, and GO)

Protein Q9NYA1 (Reactome details) participates in the following event(s):

R-HSA-391266 Association of CCT/TriC with sphingosine kinase 1
R-HSA-5218823 PKC phosphorylates sphingosine kinase 1
R-HSA-5218845 p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate
R-HSA-428214 sphinganine (dihydrosphingosine) +ATP => sphinganine 1-phosphate + ADP
R-HSA-428273 sphingosine +ATP => sphingosine 1-phosphate + ADP
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-390466 Chaperonin-mediated protein folding
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-1660661 Sphingolipid de novo biosynthesis
R-HSA-391251 Protein folding
R-HSA-194138 Signaling by VEGF
R-HSA-428157 Sphingolipid metabolism
R-HSA-392499 Metabolism of proteins
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-556833 Metabolism of lipids
R-HSA-162582 Signal Transduction
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: NM_001142601, Q8N632, Q9HD92, Q9NY70, Q9NYA1, Q9NYL3, SPHK, SPHK1_HUMAN, SPK, uc002jri.1, uc002jri.2
UCSC ID: uc002jri.2
RefSeq Accession: NM_001142601
Protein: Q9NYA1 (aka SPHK1_HUMAN or SPH1_HUMAN)
CCDS: CCDS45785.1, CCDS59297.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.