SPHK1
Sphingosine kinase 1
Also known as: SPHK, SPHK1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9NYA1
- Gene
- SPHK1
- Ensembl
- ENSG00000176170
- Chromosome
- 17
- Canonical length
- 384 aa
- Protein class
- Enzymes, Metabolic proteins, Predicted intracellular proteins
- Subcellular location
- Vesicles,Plasma membrane,Primary cilium,Primary cilium transition zone
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
384 residues, UniProt reviewed canonical sequence.
>Q9NYA1|SPHK1
1 MDPAGGPRGV LPRPCRVLVL LNPRGGKGKA LQLFRSHVQP LLAEAEISFT LMLTERRNHA
61 RELVRSEELG RWDALVVMSG DGLMHEVVNG LMERPDWETA IQKPLCSLPA GSGNALAASL
121 NHYAGYEQVT NEDLLTNCTL LLCRRLLSPM NLLSLHTASG LRLFSVLSLA WGFIADVDLE
181 SEKYRRLGEM RFTLGTFLRL AALRTYRGRL AYLPVGRVGS KTPASPVVVQ QGPVDAHLVP
241 LEEPVPSHWT VVPDEDFVLV LALLHSHLGS EMFAAPMGRC AAGVMHLFYV RAGVSRAMLL
301 RLFLAMEKGR HMEYECPYLV YVPVVAFRLE PKDGKGVFAV DGELMVSEAV QGQVHPNYFW
361 MVSGCVEPPP SWKPQQMPPP EEPLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SPHK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.25
- Highest tissue expression
- 24 nTPM
Expression across tissuesHPA
Tissue
- lung: 24 nTPM
- esophagus: 24 nTPM
- salivary gland: 19 nTPM
- adipose tissue: 19 nTPM
- heart muscle: 17 nTPM
- breast: 17 nTPM
Single-cell type
- esophageal apical cells: 195 nCPM
- müller glia: 142 nCPM
- platelets: 132 nCPM
- breast secretory cells: 104 nCPM
- decidual stromal cells: 86 nCPM
- pancreatic duct cells: 78 nCPM
Immune cell
- plasmacytoid DC: 4.8 nTPM
- classical monocyte: 1.9 nTPM
- basophil: 1.5 nTPM
- intermediate monocyte: 0.9 nTPM
- gdT-cell: 0.8 nTPM
- total PBMC: 0.8 nTPM
Brain region
- thalamus: 19 nTPM
- cerebral cortex: 11 nTPM
- pons: 9.6 nTPM
- medulla oblongata: 8.8 nTPM
- midbrain: 8.8 nTPM
- amygdala: 8.5 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.41
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.49
- DepMap mean gene effect
- -0.07
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- blood vessel development
- brain development
- calcium-mediated signaling
- cell population proliferation
- cellular response to growth factor stimulus
- cellular response to hydrogen peroxide
- cellular response to vascular endothelial growth factor stimulus
- DNA biosynthetic process
- inflammatory response
- intracellular signal transduction
- negative regulation of apoptotic process
- negative regulation of ceramide biosynthetic process
- positive regulation of angiogenesis
- positive regulation of cell growth
- positive regulation of cell migration
- positive regulation of fibroblast proliferation
- positive regulation of interleukin-17 production
- positive regulation of mitotic cell cycle
- positive regulation of mitotic nuclear division
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of p38MAPK cascade
- positive regulation of protein ubiquitination
- positive regulation of smooth muscle contraction
- protein acetylation
- regulation of endocytosis
- regulation of interleukin-1 beta production
- regulation of microglial cell activation
- regulation of neuroinflammatory response
- regulation of phagocytosis
- regulation of tumor necrosis factor-mediated signaling pathway
- response to tumor necrosis factor
- sphingolipid biosynthetic process
- sphingosine biosynthetic process
- sphingosine metabolic process
- regulation of endosomal vesicle fusion
- sphingoid catabolic process
Molecular functions
- acetyltransferase activity
- ATP binding
- calmodulin binding
- DNA binding
- lipid binding
- lipid kinase activity
- magnesium ion binding
- protein phosphatase 2A binding
- sphingosine kinase activity
- sphingosine-1-phosphate receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SPHK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SPHK1 as an antibody target. Whether an autoantibody or antibody against SPHK1 could matter depends on whether native SPHK1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SPHK1 is annotated at the cell surface, where native SPHK1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label SPHK1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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