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SPHK1 sphingosine kinase 1 [ Homo sapiens (human) ]

Gene ID: 8877, updated on 11-Sep-2019

Summary

Official Symbol
SPHK1provided by HGNC
Official Full Name
sphingosine kinase 1provided by HGNC
Primary source
HGNC:HGNC:11240
See related
Ensembl:ENSG00000176170 MIM:603730
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SPHK
Summary
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]
Expression
Ubiquitous expression in gall bladder (RPKM 4.9), esophagus (RPKM 4.2) and 25 other tissues See more
Orthologs

Genomic context

See SPHK1 in Genome Data Viewer
Location:
17q25.1
Exon count:
7
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 17 NC_000017.11 (76383204..76387855)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (74372742..74383941)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene phosphoribosyl pyrophosphate synthetase associated protein 1 Neighboring gene RNA, U6 small nuclear 24, pseudogene Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 43 Neighboring gene ubiquitin conjugating enzyme E2 O Neighboring gene ribosomal protein L7 pseudogene 49 Neighboring gene aralkylamine N-acetyltransferase

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of sphingosine kinase 1 (SPHK1) in human B cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Apelin signaling pathway, organism-specific biosystem (from KEGG)
    Apelin signaling pathway, organism-specific biosystemApelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various ti...
  • Association of TriC/CCT with target proteins during biosynthesis, organism-specific biosystem (from REACTOME)
    Association of TriC/CCT with target proteins during biosynthesis, organism-specific biosystemTRiC has broad recognition specificities, but in the cell it interacts with only a defined set of substrates (Yam et al. 2008). Many of its substrates that are targeted during biosynthesis are conse...
  • Calcium signaling pathway, organism-specific biosystem (from KEGG)
    Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
  • Calcium signaling pathway, conserved biosystem (from KEGG)
    Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
  • Chaperonin-mediated protein folding, organism-specific biosystem (from REACTOME)
    Chaperonin-mediated protein folding, organism-specific biosystemThe eukaryotic chaperonin TCP-1 ring complex (TRiC/ CCT) plays an essential role in the folding of a subset of proteins prominent among which are the actins and tubulins (reviewed in Altschuler and...
  • Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
    Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
    Fc-epsilon receptor I signaling in mast cells
  • Metabolic pathways, organism-specific biosystem (from KEGG)
    Metabolic pathways, organism-specific biosystem
    Metabolic pathways
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
    Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • PDGFR-beta signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    PDGFR-beta signaling pathway, organism-specific biosystem
    PDGFR-beta signaling pathway
  • Phospholipase D signaling pathway, organism-specific biosystem (from KEGG)
    Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
  • Phospholipase D signaling pathway, conserved biosystem (from KEGG)
    Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
  • Protein folding, organism-specific biosystem (from REACTOME)
    Protein folding, organism-specific biosystemDue to the crowded envirnoment within the cell, many proteins must interact with molecular chaperones to attain their native conformation (reviewed in Young et al., 2004). Chaperones recognize and...
  • S1P1 pathway, organism-specific biosystem (from Pathway Interaction Database)
    S1P1 pathway, organism-specific biosystem
    S1P1 pathway
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signal Transduction of S1P Receptor, organism-specific biosystem (from WikiPathways)
    Signal Transduction of S1P Receptor, organism-specific biosystemMetabolism of sphingomyelin by the sphingomyelinase, ceramidase (Cer'ase) and the sphingosine kinase (SK) enzymes results in formation of S1P and receptor activation. Autocrine and paracrine modes of...
  • Signaling by VEGF, organism-specific biosystem (from REACTOME)
    Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
  • Sphingolipid Metabolism, organism-specific biosystem (from WikiPathways)
    Sphingolipid Metabolism, organism-specific biosystemThe sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form ...
  • Sphingolipid de novo biosynthesis, organism-specific biosystem (from REACTOME)
    Sphingolipid de novo biosynthesis, organism-specific biosystemThe main steps involved in de novo sphingolipid synthesis are annotated here (Merrill 2002, Gault et al. 2010).
  • Sphingolipid metabolism, organism-specific biosystem (from KEGG)
    Sphingolipid metabolism, organism-specific biosystem
    Sphingolipid metabolism
  • Sphingolipid metabolism, organism-specific biosystem (from REACTOME)
    Sphingolipid metabolism, organism-specific biosystemSphingolipids are derivatives of long chain sphingoid bases such as sphingosine (trans-1,3-dihydroxy 2-amino-4-octadecene), an 18-carbon unsaturated amino alcohol which is the most abundant sphingoid...
  • Sphingolipid metabolism, conserved biosystem (from KEGG)
    Sphingolipid metabolism, conserved biosystem
    Sphingolipid metabolism
  • Sphingolipid signaling pathway, organism-specific biosystem (from KEGG)
    Sphingolipid signaling pathway, organism-specific biosystemSphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) ...
  • Sphingolipid signaling pathway, conserved biosystem (from KEGG)
    Sphingolipid signaling pathway, conserved biosystemSphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) ...
  • Sphingosine 1-phosphate (S1P) pathway, organism-specific biosystem (from Pathway Interaction Database)
    Sphingosine 1-phosphate (S1P) pathway, organism-specific biosystem
    Sphingosine 1-phosphate (S1P) pathway
  • Sphingosine degradation, organism-specific biosystem (from KEGG)
    Sphingosine degradation, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
  • Sphingosine degradation, conserved biosystem (from KEGG)
    Sphingosine degradation, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • VEGF signaling pathway, organism-specific biosystem (from KEGG)
    VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
  • VEGF signaling pathway, conserved biosystem (from KEGG)
    VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
  • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
    VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
  • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
    VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
  • sphingosine and sphingosine-1-phosphate metabolism, organism-specific biosystem (from BIOCYC)
    sphingosine and sphingosine-1-phosphate metabolism, organism-specific biosystemIn this pathway, ceramide, the breakdown product of sphingomyelin, is metabolized by ceramidase to generate : SPHINGOSINE, which has been shown to be produced during the early stages of apoptosis; : ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IDA
Inferred from Direct Assay
more info
PubMed 
D-erythro-sphingosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
D-erythro-sphingosine kinase activity TAS
Traceable Author Statement
more info
 
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
NAD+ kinase activity IEA
Inferred from Electronic Annotation
more info
 
acetyltransferase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
calmodulin binding IDA
Inferred from Direct Assay
more info
PubMed 
lipid binding IDA
Inferred from Direct Assay
more info
PubMed 
magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein phosphatase 2A binding IPI
Inferred from Physical Interaction
more info
PubMed 
sphinganine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
sphingosine-1-phosphate receptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Process Evidence Code Pubs
DNA biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
blood vessel development IEA
Inferred from Electronic Annotation
more info
 
brain development IEA
Inferred from Electronic Annotation
more info
 
calcium-mediated signaling IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to hydrogen peroxide IEA
Inferred from Electronic Annotation
more info
 
cellular response to vascular endothelial growth factor stimulus IDA
Inferred from Direct Assay
more info
PubMed 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction TAS
Traceable Author Statement
more info
PubMed 
lipid phosphorylation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of ceramide biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of NIK/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell growth IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of fibroblast proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-17 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of mitotic cell cycle IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of mitotic nuclear division IEA
Inferred from Electronic Annotation
more info
 
positive regulation of p38MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-threonine phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of smooth muscle contraction IDA
Inferred from Direct Assay
more info
PubMed 
protein acetylation ISS
Inferred from Sequence or Structural Similarity
more info
 
protein folding TAS
Traceable Author Statement
more info
 
regulation of endocytosis IDA
Inferred from Direct Assay
more info
PubMed 
regulation of endosomal vesicle fusion ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of interleukin-1 beta production IEA
Inferred from Electronic Annotation
more info
 
regulation of microglial cell activation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of neuroinflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of phagocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of tumor necrosis factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
response to tumor necrosis factor IDA
Inferred from Direct Assay
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
sphingoid catabolic process NAS
Non-traceable Author Statement
more info
PubMed 
sphingolipid biosynthetic process TAS
Traceable Author Statement
more info
 
sphingosine biosynthetic process IGI
Inferred from Genetic Interaction
more info
PubMed 
sphingosine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
sphingosine metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
sphingosine-1-phosphate receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cell junction IEA
Inferred from Electronic Annotation
more info
 
clathrin-coated pit IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
PubMed 
early endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
endocytic vesicle ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
presynapse ISS
Inferred from Sequence or Structural Similarity
more info
 

General protein information

Preferred Names
sphingosine kinase 1
Names
SK 1
SPK 1
acetyltransferase SPHK1
NP_001136073.1
NP_001136074.1
NP_001342068.1
NP_068807.2
NP_892010.2

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001142601.2NP_001136073.1  sphingosine kinase 1 isoform 3

    See identical proteins and their annotated locations for NP_001136073.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate in-frame segment in the 5' coding region and uses a downstream start codon, compared to variant 2. Isoform 3 has a shorter N-terminus, compared to isoform 2. Variants 3, 4 and 5 encode the same isoform (3).
    Source sequence(s)
    AK022402, BC030553, DC384776
    Consensus CDS
    CCDS45785.1
    UniProtKB/Swiss-Prot
    Q9NYA1
    UniProtKB/TrEMBL
    Q53ZR5
    Related
    ENSP00000465726.1, ENST00000592299.5
    Conserved Domains (1) summary
    cl27661
    Location:11345
    LCB5; Diacylglycerol kinase family enzyme [Lipid transport and metabolism, General function prediction only]
  2. NM_001142602.2NP_001136074.1  sphingosine kinase 1 isoform 3

    See identical proteins and their annotated locations for NP_001136074.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate in-frame segment in the 5' coding region and uses a downstream start codon, compared to variant 2. Isoform 3 has a shorter N-terminus, compared to isoform 2. Variants 3, 4 and 5 encode the same isoform (3).
    Source sequence(s)
    BC030553, BP304783, DC384776
    Consensus CDS
    CCDS45785.1
    UniProtKB/Swiss-Prot
    Q9NYA1
    UniProtKB/TrEMBL
    Q53ZR5
    Related
    ENSP00000376285.2, ENST00000392496.3
    Conserved Domains (1) summary
    cl27661
    Location:11345
    LCB5; Diacylglycerol kinase family enzyme [Lipid transport and metabolism, General function prediction only]
  3. NM_001355139.2NP_001342068.1  sphingosine kinase 1 isoform 3

    Status: REVIEWED

    Source sequence(s)
    BC030553, DA482243, DC384776
    Consensus CDS
    CCDS45785.1
    Conserved Domains (1) summary
    cl27661
    Location:11345
    LCB5; Diacylglycerol kinase family enzyme [Lipid transport and metabolism, General function prediction only]
  4. NM_021972.4NP_068807.2  sphingosine kinase 1 isoform 1

    See identical proteins and their annotated locations for NP_068807.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) has multiple differences in the coding region, compared to variant 2. The resulting protein (isoform 1) has a shorter N-terminus and contains an additional in-frame portion of the 5' coding region, compared to isoform 2.
    Source sequence(s)
    AK022402, BC009419, BC030553, DC384776
    Consensus CDS
    CCDS59297.1
    UniProtKB/Swiss-Prot
    Q9NYA1
    Related
    ENSP00000468547.1, ENST00000590959.5
    Conserved Domains (1) summary
    cl27661
    Location:25359
    LCB5; Diacylglycerol kinase family enzyme [Lipid transport and metabolism, General function prediction only]
  5. NM_182965.3NP_892010.2  sphingosine kinase 1 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).
    Source sequence(s)
    AK022402, BC030553, DC384776
    Consensus CDS
    CCDS11744.1
    UniProtKB/Swiss-Prot
    Q9NYA1
    Related
    ENSP00000313681.3, ENST00000323374.8
    Conserved Domains (2) summary
    PLN02958
    Location:97431
    PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
    pfam00781
    Location:102207
    DAGK_cat; Diacylglycerol kinase catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p13 Primary Assembly

    Range
    76383204..76387855
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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