SPHK1
entrez
8877
canonical
uniprot
Q9NYA1
canonical
ensembl
ENSG00000176170
resolver
ensp
ENSP00000313681
resolver
ensp
ENSP00000376285
resolver
ensp
ENSP00000465726
resolver
ensp
ENSP00000468547
resolver
ensp
ENSP00000559818
resolver
genesymbol
SPHK1
resolver
genesymbol_syn
SK1
resolver
genesymbol_syn
SPHK
resolver
genesymbol_syn
SPK
resolver
hgnc
HGNC:11240
resolver
uniprot
Q53ZR5
resolver
uniprot
Q8N632
resolver
uniprot
Q96GK1
resolver
uniprot
Q9HD92
resolver
uniprot
Q9NY70
resolver
uniprot
Q9NYL3
resolver
uniprot_entry
Q53ZR5_HUMAN
resolver
uniprot_entry
SPHK1_HUMAN
resolver
uniprot_sec
Q8N632
resolver
uniprot_sec
Q96GK1
resolver
uniprot_sec
Q9HD92
resolver
uniprot_sec
Q9NY70
resolver
uniprot_sec
Q9NYL3
resolver
activity_regulation
ACTIVITY REGULATION: Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (By similarity). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity). {ECO:0000250|UniProtKB:Q8CI15, ECO:0000250|UniProtKB:Q91V26, ECO:0000269|PubMed:25417698}.
uniprot
proteins
amino_acid_sequence
MDPAGGPRGVLPRPCRVLVLLNPRGGKGKALQLFRSHVQPLLAEAEISFTLMLTERRNHARELVRSEELGRWDALVVMSGDGLMHEVVNGLMERPDWETAIQKPLCSLPAGSGNALAASLNHYAGYEQVTNEDLLTNCTLLLCRRLLSPMNLLSLHTASGLRLFSVLSLAWGFIADVDLESEKYRRLGEMRFTLGTFLRLAALRTYRGRLAYLPVGRVGSKTPASPVVVQQGPVDAHLVPLEEPVPSHWTVVPDEDFVLVLALLHSHLGSEMFAAPMGRCAAGVMHLFYVRAGVSRAMLLRLFLAMEKGRHMEYECPYLVYVPVVAFRLEPKDGKGVFAVDGELMVSEAVQGQVHPNYFWMVSGCVEPPPSWKPQQMPPPEEPL
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
2.7.1.91
uniprot
proteins
function
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 (PubMed:11923095, PubMed:20577214, PubMed:23602659, PubMed:24929359, PubMed:29662056). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:24929359, PubMed:28049734). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698). {ECO:0000269|PubMed:11923095, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23602659, ECO:0000269|PubMed:23935096, ECO:0000269|PubMed:24929359, ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:28049734, ECO:0000269|PubMed:29662056}.; FUNCTION: Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia. {ECO:0000250|UniProtKB:Q8CI15}.
uniprot
proteins
mass_dalton
42518
uniprot
proteins
mutagenesis
MUTAGEN 81; /note="D->A: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:23602659"; MUTAGEN 81; /note="D->N: Strongly reduced enzyme activity."; /evidence="ECO:0000269|PubMed:23602659"; MUTAGEN 82; /note="G->D: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:20577214"; MUTAGEN 194; /note="L->Q: Loss of binding to negatively charged membranes, diffuse cytosolic distribution."; /evidence="ECO:0000269|PubMed:24929359"; MUTAGEN 197..198; /note="FL->AA: Abolishes interaction with CIB1."; /evidence="ECO:0000269|PubMed:19854831"; MUTAGEN 197..198; /note="FL->AQ: Loss of binding to negatively charged membranes, diffuse cytosolic distribution."; /evidence="ECO:0000269|PubMed:24929359
uniprot
proteins
pubmed
10802064
uniprot
proteins
pubmed
10863092
uniprot
proteins
pubmed
10947957
uniprot
proteins
pubmed
11923095
uniprot
proteins
pubmed
12080051
uniprot
proteins
pubmed
14575709
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16118219
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
18263879
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19854831
uniprot
proteins
pubmed
20577214
uniprot
proteins
pubmed
23602659
uniprot
proteins
pubmed
23935096
uniprot
proteins
pubmed
24929359
uniprot
proteins
pubmed
25417698
uniprot
proteins
pubmed
28049734
uniprot
proteins
pubmed
29662056
uniprot
proteins
sequence_length
384
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14575709, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:29662056}. Nucleus {ECO:0000269|PubMed:14575709, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:29662056}. Cell membrane {ECO:0000269|PubMed:19854831}. Endosome membrane {ECO:0000269|PubMed:24929359}; Peripheral membrane protein {ECO:0000269|PubMed:24929359}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:24929359}. Synapse {ECO:0000250|UniProtKB:Q8CI15}. Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner (PubMed:19854831). Binds to membranes containing negatively charged lipids but not neutral lipids (PubMed:24929359). Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity). {ECO:0000250|UniProtKB:Q8CI15, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:24929359}.
uniprot
proteins