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Symbol SPHK1 contributors: mct/npt - updated : 25-01-2014
HGNC name sphingosine kinase 1
HGNC id 11240
Location 17q25.1      Physical location : 74.380.689 - 74.383.941
Synonym symbol(s) SPHK, SK-1, SPK1, SPK
TYPE functioning gene
STRUCTURE 3.25 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   HRE
text structure two putative hypoxia-inducible factor-responsive-elements (HRE)
MAPPING cloned Y linked N status provisional
Physical map
ITGB4 17q24.3 integrin, beta 4 GALK1 17q24 galactokinase 1 H3F3B 17q25 H3 histone, family 3B (H3.3B) KIAA1753 17q25.3 KIAA1753 protein UNC13D 17q25.3 unc-13 homolog D (C. elegans) WBP2 17q25 WW domain binding protein 2 TRIM47 17q24.q25 tripartite motif-containing 47 LOC201292 17q25.3 hypothetical protein LOC201292 MRPL38 17q23-q25 mitochondrial ribosomal protein L38 FBF-1 17q25.3 Fas binding protein 1 ACOX1 17q25.1 acyl-Coenzyme A oxidase 1, palmitoyl CDK3 17q25 cyclin-dependent kinase 3 EVPL 17q24.2-q24.3 envoplakin SRP68 17q25,1 signal recognition particle 68kDa GALR2 17q25.3 galanin receptor 2 LGICZ 17q25.3 ligand-gated ion channel subunit EXO70 17q25.3 ligand-gated ion channel subunit FOXJ1 17q forkhead box J1 KIAA1917 17q25.3 KIAA1917 protein MGC29814 17q25.3 hypothetical protein MGC29814 DKFZP434P0316 17q25.3 hypothetical protein DKFZp434P0316 PRPSAP1 17q24-q25 phosphoribosyl pyrophosphate synthetase-associated protein 1 SPHK1 17q25.2 sphingosine kinase 1 E2-230K 17q25.1 likely ortholog of mouse ubiquitin-conjugating enzyme E2-230K AANAT 17q25 arylalkylamine N-acetyltransferase FLJ22341 17q25.3 hypothetical protein FLJ22341 CYGB 17q25.3 cytoglobin STHM 17q25.3 cytoglobin SIAT7A 17q25.3 sialyltransferase 7 ((alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3)-N-acetyl galactosaminide alpha-2,6-sialyltransferase) A FLJ46603 17q25.3 FLJ46603 protein PTDSR 17q25 phosphatidylserine receptor SFRS2 17q25.1 splicing factor, arginine/serine-rich 2 ET 17q25 hypothetical protein ET LOC283994 17q25.3 hypothetical protein LOC283994 GnT-IX 17q25.3 beta(1,6)-N-acetylglucosaminyltransferase V
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 splicing 1881 43.8 398 - 2000 10751414
6 splicing 2174 51 470 - 2000 10751414
5 - 1884 - 384 - 2000 10751414
6 - 1839 - 384 - 2000 10751414
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   highly
Digestiveesophagus   predominantly
 salivary gland   moderately
Endocrinethyroid   highly
Reproductivefemale systemuteruscervix highly
 respiratory tractlarynx  moderately
Skin/Tegumentskin   highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
cell lineage
cell lines
physiological period fetal
Text highly in umbilical cord
  • diacylglycerol kinase catalytic domain
  • two functional nuclear export signal (NES) sequences in the middle region
    interspecies homolog to rattus Sphk1 (78.6 pc)
    homolog to murine Sphk1 (81.2 pc)
  • lipid kinase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
  • shuttles between the cytoplasm and the nucleus
  • whereas its localization does not affect downstream metabolism of sphingosine-1-phosphate, localization has an important effect on the pools of substrate to which this key signaling enzyme has access
  • basic FUNCTION
  • catalyzing the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP) involved in a variety of cellular processes
  • enhanced by exposition to mitogenic agents
  • playing an essential role in neural and vascular development
  • lipid kinase implicated in mitogenic signaling pathways in vascular smooth muscle cells
  • cytosolic enzyme that is recruited to the plasma membrane following its phosphorylation in response to growth stimuli
  • role of SPHK1 and its product SGPP1 in TNF1 signalling and the canonical NFkB activation pathway important in inflammatory, antiapoptotic and immune processes
  • implicated DEFB4A regulation in oral keratinocytes
  • its over-expression in human endothelial cells promotes, in part, their de-differentiation to a progenitor cell phenotype, and is thus a potential tool for the generation of a large population of vascular progenitor cells
  • plays a critical role in matrix accumulation in glomerular mesangial cells
  • under diabetic condition
  • SPHK1/S1P signaling plays an important role in regulating early events during development of sensory ganglia
  • key enzyme in the sphingolipid metabolic pathway, forming an essential checkpoint to regulate the relative levels of bioactive sphingolipid metabolites, ceramide, sphingosine, and sphingosine 1-phosphate (S1P)
  • SPHK1 acetylation plays a key role in cell growth, cell size, and cell-cycle control
  • SPHK1-produced S1P is a crucial mediator of breast cancer-induced hemangiogenesis and lymphangiogenesis
  • endothelial SKPH1 is an important contributor to allergic inflammation
  • important role for S1PR4 and SPHK1 in oestrogen receptor-negative breast cancer progression
  • its activation is involved in the regulation of lipopolysaccharide-induced brain injury
  • important enzyme involved in the production of the bioactive lipid sphingosine 1-phosphate (S1P)
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell life, proliferation/growth
    cell life, antiapoptosis
    cell migration & motility
  • positive regulation of angiogenesis
  • positive regulation of cell growth
  • positive regulation of cell migration
  • positive regulation of fibroblast proliferation
  • positive regulation of mitotic cell cycle
  • positive regulation of smooth muscle contraction
    metabolism lipid/lipoprotein
    signaling signal transduction
  • neuronal survival pathway
  • G-protein coupled receptor protein signaling pathway
  • calcium-mediated signaling
  • intracellular signaling cascade
  • sphingoid catabolic process
  • sphingosine metabolic process
  • PI3K/AKT/MTOR signaling pathway is involved in regulation of SPHK1, with AKT2 playing a key role in PDGF-induced SPHK1 expression in coronary artery smooth muscle cells
  • a component
    small molecule cofactor, nucleotide,
  • Mg2+
  • ATP
  • protein
  • interacting with TIMP1 (positive regulator of TIMP1 gene expression)
  • binding to calmodulin
  • interacting with ACY1
  • interacting with SPHKAP
  • EEF1A1 interacts with and directly activates SPHK1
  • GDNF increased SPHK1 transcription, leading to the production and secretion of S1P
  • oncogenic KRAS regulates bioactive sphingolipids in a sphingosine kinase 1-dependent manner
  • TFRC has an important role in SPHK1-mediated oncogenesis
  • ANKH /MYBBP1A and SPHK1 interactions stimulate catabolic events in IL1B-mediated cartilage degradation
  • ADORA2B is essential for adenosine-induced SPHK1 activity in normal and sickle erythrocytes
  • cell & other
    activated by multiple stimuli, including growth factors, and inflammatory mediators such as TNF1 and IgE
    induced by a variety of factors including PDGF, phosphatidylserine, etc..
    hypoxia via HIF-1alpha and HIF-2alpha expression
    Other regulation mediated by interaction with EEF1A1
    regulated by PPP2CA (endogenous regulator of SPHK1 phosphorylation)
    acetylated by the intrinsic acetyltransferase activity of EP300/CREB-binding protein (CBP) at a conserved acetylation motif (the GK motif)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    and promotes proliferation in human thyroid cancer
    Variant & Polymorphism
    Candidate gene
    Therapy target
    overexpression of SPHK1 might be a potential new treatment approach to neuroinflammation
    SPHK1 along with S1P are therapeutic targets in breast cancer
    diabetetype 1 
    could be a potential therapeutic target for diabetic nephropathy