Browse SPHK1

Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Cell membrane. Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner.
Domain PF00781 Diacylglycerol kinase catalytic domain
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.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001558 regulation of cell growth
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0003012 muscle system process
GO:0003376 sphingosine-1-phosphate signaling pathway
GO:0006066 alcohol metabolic process
GO:0006457 protein folding
GO:0006606 protein import into nucleus
GO:0006643 membrane lipid metabolic process
GO:0006665 sphingolipid metabolic process
GO:0006670 sphingosine metabolic process
GO:0006913 nucleocytoplasmic transport
GO:0006936 muscle contraction
GO:0006937 regulation of muscle contraction
GO:0006939 smooth muscle contraction
GO:0006940 regulation of smooth muscle contraction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007346 regulation of mitotic cell cycle
GO:0010799 regulation of peptidyl-threonine phosphorylation
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0016042 lipid catabolic process
GO:0016049 cell growth
GO:0017038 protein import
GO:0018107 peptidyl-threonine phosphorylation
GO:0018210 peptidyl-threonine modification
GO:0019722 calcium-mediated signaling
GO:0019751 polyol metabolic process
GO:0019932 second-messenger-mediated signaling
GO:0030148 sphingolipid biosynthetic process
GO:0030149 sphingolipid catabolic process
GO:0030258 lipid modification
GO:0030307 positive regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0031503 protein complex localization
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032611 interleukin-1 beta production
GO:0032612 interleukin-1 production
GO:0032651 regulation of interleukin-1 beta production
GO:0032652 regulation of interleukin-1 production
GO:0033157 regulation of intracellular protein transport
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034311 diol metabolic process
GO:0034312 diol biosynthetic process
GO:0034504 protein localization to nucleus
GO:0034612 response to tumor necrosis factor
GO:0040017 positive regulation of locomotion
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042345 regulation of NF-kappaB import into nucleus
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0042348 NF-kappaB import into nucleus
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044057 regulation of system process
GO:0044242 cellular lipid catabolic process
GO:0044283 small molecule biosynthetic process
GO:0044744 protein targeting to nucleus
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045787 positive regulation of cell cycle
GO:0045927 positive regulation of growth
GO:0045931 positive regulation of mitotic cell cycle
GO:0045933 positive regulation of muscle contraction
GO:0045987 positive regulation of smooth muscle contraction
GO:0046165 alcohol biosynthetic process
GO:0046173 polyol biosynthetic process
GO:0046466 membrane lipid catabolic process
GO:0046467 membrane lipid biosynthetic process
GO:0046512 sphingosine biosynthetic process
GO:0046519 sphingoid metabolic process
GO:0046520 sphingoid biosynthetic process
GO:0046521 sphingoid catabolic process
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046834 lipid phosphorylation
GO:0048144 fibroblast proliferation
GO:0048145 regulation of fibroblast proliferation
GO:0048146 positive regulation of fibroblast proliferation
GO:0048514 blood vessel morphogenesis
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051272 positive regulation of cellular component movement
GO:0060759 regulation of response to cytokine stimulus
GO:0071356 cellular response to tumor necrosis factor
GO:0090257 regulation of muscle system process
GO:0090316 positive regulation of intracellular protein transport
GO:0090520 sphingolipid mediated signaling pathway
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901342 regulation of vasculature development
GO:1901565 organonitrogen compound catabolic process
GO:1901615 organic hydroxy compound metabolic process
GO:1901617 organic hydroxy compound biosynthetic process
GO:1902593 single-organism nuclear import
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903533 regulation of protein targeting
GO:1903829 positive regulation of cellular protein localization
GO:1904018 positive regulation of vasculature development
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904951 positive regulation of establishment of protein localization
GO:2000147 positive regulation of cell motility
Molecular Function GO:0000287 magnesium ion binding
GO:0001727 lipid kinase activity
GO:0005516 calmodulin binding
GO:0008481 sphinganine kinase activity
GO:0017050 D-erythro-sphingosine kinase activity
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0038036 sphingosine-1-phosphate receptor activity
GO:0045125 bioactive lipid receptor activity
GO:0051721 protein phosphatase 2A binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04020 Calcium signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04370 VEGF signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis
hsa00600 Sphingolipid metabolism
hsa01100 Metabolic pathways
Reactome R-HSA-390471: Association of TriC/CCT with target proteins during biosynthesis
R-HSA-390466: Chaperonin-mediated protein folding
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-392499: Metabolism of proteins
R-HSA-391251: Protein folding
R-HSA-162582: Signal Transduction
R-HSA-194138: Signaling by VEGF
R-HSA-1660661: Sphingolipid de novo biosynthesis
R-HSA-428157: Sphingolipid metabolism
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SPHK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SPHK1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23373542Breast Carcinoma; Osteosarcoma; Pancreatic AdenocarcinomaPromote immunityMechanistically, PhotoImmunoNanoTherapy induced a sphingosine kinase 2-dependent increase in sphingosine-1-phosphate and dihydrosphingosine-1-phosphate. Furthermore, dihydrosphingosine-1-phosphate was shown to selectively abrogate myeloid lineage cells while concomitantly allowing the expansion of lymphocytes that exerted an antitumor effect.
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SPHK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SPHK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.8080.167
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8050.739
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.7970.623
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.9160.175
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.0670.562
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.7140.782
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.2710.592
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.4840.681
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0150.991
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6740.611
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4230.824
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3870.0595
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SPHK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.407.40.0709
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.407.40.096
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPHK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPHK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPHK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPHK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SPHK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SPHK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSPHK1
Namesphingosine kinase 1
Aliases SPHK; SPK 1
Chromosomal Location17q25.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SPHK1 collected from DrugBank database.
> Drugs from DrugBank database
 

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