SPHK2
entrez
56848
canonical
uniprot
Q9NRA0
canonical
ensembl
ENSG00000063176
resolver
ensp
ENSP00000245222
resolver
ensp
ENSP00000341091
resolver
ensp
ENSP00000469158
resolver
ensp
ENSP00000470092
resolver
ensp
ENSP00000471205
resolver
enst
ENST00000340932
resolver
genesymbol
SPHK2
resolver
genesymbol_syn
SK2
resolver
hgnc
HGNC:18859
resolver
uniprot
A0T4C8
resolver
uniprot
B3KV83
resolver
uniprot
B4DU87
resolver
uniprot
E9PCV4
resolver
uniprot
Q9BRN1
resolver
uniprot
Q9H0Q2
resolver
uniprot
Q9NWU7
resolver
uniprot_entry
B3KV83_HUMAN
resolver
uniprot_entry
E9PCV4_HUMAN
resolver
uniprot_entry
SPHK2_HUMAN
resolver
uniprot_sec
A0T4C8
resolver
uniprot_sec
B4DU87
resolver
uniprot_sec
Q9BRN1
resolver
uniprot_sec
Q9H0Q2
resolver
uniprot_sec
Q9NWU7
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by sulfatide (PubMed:19168031). Kinase activity is increased by phosphorylation by MAPK2 upon PMA or EGF treatments (PubMed:17311928). {ECO:0000269|PubMed:17311928, ECO:0000269|PubMed:19168031}.
uniprot
proteins
amino_acid_sequence
MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPARGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTYPRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRPPRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDGIVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDLLLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTLGTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSVSDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKAALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVLMLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQLGYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP
uniprot
proteins
disease_involvement
DISEASE: Note=In patients with Alzheimer's disease brains, may be preferentially localized in the nucleus. Cytosolic expression decrease correlates with the density of amyloid deposits. {ECO:0000269|PubMed:29615132}.
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-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:12954646, PubMed:19168031). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9JIA7, ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20959514}.
uniprot
proteins
mass_dalton
69217
uniprot
proteins
mutagenesis
MUTAGEN 138; /note="D->A: Abolishes cleavage and secretion in apoptotic cells. No effect on kinase activity."; /evidence="ECO:0000269|PubMed:20197547"; MUTAGEN 212; /note="G->E: Decreases SPP production in nucleus. Abolishes increase of histone acetylation. No effect on association with histone 3."; /evidence="ECO:0000269|PubMed:19729656"; MUTAGEN 220; /note="T->A: Loss of location to cell membrane. Not secreted. No effect on kinase activity."; /evidence="ECO:0000269|PubMed:20197547"; MUTAGEN 387; /note="S->A: Strongly reduces phosphorylation levels."; /evidence="ECO:0000269|PubMed:17311928"; MUTAGEN 419..421; /note="SVS->AVA: Abolishes nuclear export in response to PMA treatment."; /evidence="ECO:0000269|PubMed:17635916"; MUTAGEN 423..425; /note="LPL->APA: Abolishes nuclear export."; /evidence="ECO:0000269|PubMed:17635916"; MUTAGEN 437; /note="S->A: Reduces phosphorylation levels."; /evidence="ECO:0000269|PubMed:17311928"; MUTAGEN 466; /note="S->A: Reduces phosphorylation levels."; /evidence="ECO:0000269|PubMed:17311928"; MUTAGEN 477; /note="S->A: Reduces phosphorylation levels."; /evidence="ECO:0000269|PubMed:17311928"; MUTAGEN 552; /note="D->A: No effect on cleavage and secretion in apoptotic cells. No effect on kinase activity."; /evidence="ECO:0000269|PubMed:20197547"; MUTAGEN 614; /note="T->A: Abolishes phosphorylation."; /evidence="ECO:0000269|PubMed:17311928
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PKD on Ser-419 and Ser-421 upon PMA treatment. Phosphorylation induces export from the nucleus to the cytoplasm (PubMed:17635916). Phosphorylated by MAPK1 and MAPK2 at Ser-387 and Thr-614, phosphorylation is induced by agonists such as EGF and PMA and increases kinase activity (PubMed:17311928). {ECO:0000269|PubMed:17311928, ECO:0000269|PubMed:17635916}.; PTM: Cleaved by CASP1 in apoptotic cells. The truncated form is released from cells. {ECO:0000269|PubMed:20197547}.
uniprot
proteins
pubmed
10751414
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
12954646
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16103110
uniprot
proteins
pubmed
16118219
uniprot
proteins
pubmed
17311928
uniprot
proteins
pubmed
17635916
uniprot
proteins
pubmed
17897319
uniprot
proteins
pubmed
18263879
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19168031
uniprot
proteins
pubmed
19729656
uniprot
proteins
pubmed
20197547
uniprot
proteins
pubmed
20959514
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
29615132
uniprot
proteins
sequence_length
654
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:17635916, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}. Nucleus {ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:17635916, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9JIA7}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q9JIA7}. Note=In nucleus, located in nucleosomes where it associates with core histone proteins such as histone 3 (PubMed:19729656). In brains of patients with Alzheimer's disease, may be preferentially localized in the nucleus. Cytosolic expression decrease correlates with the density of amyloid deposits (PubMed:29615132). In apoptotic cells, colocalizes with CASP1 in cell membrane where is cleaved and released from cells in an active form (PubMed:20197547). {ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}.; SUBCELLULAR LOCATION: [Isoform 2]: Lysosome membrane {ECO:0000269|PubMed:17897319}.
uniprot
proteins