UniProtKB - Q9JIA7 (SPHK2_MOUSE)
Protein
Sphingosine kinase 2
Gene
Sphk2
Organism
Mus musculus (Mouse)
Status
Functioni
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:16118219, PubMed:10751414). 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. Upregulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12. In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (By similarity). 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 (PubMed:17346996). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (PubMed:25637806). Also involved in the regulation of glucose and lipid metabolism (PubMed:30593892).By similarity6 Publications
Catalytic activityi
- EC:2.7.1.912 PublicationsThis reaction proceeds in the forward1 Publication direction.
- EC:2.7.1.911 PublicationThis reaction proceeds in the forward1 Publication direction.
- EC:2.7.1.911 PublicationThis reaction proceeds in the forward1 Publication direction.
- EC:2.7.1.911 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Mg2+By similarity
Kineticsi
- KM=3.4 µM for sphing-4-enine1 Publication
- Vmax=0.1 nmol/min/mg enzyme1 Publication
- Vmax=0.3 nmol/min/mg enzyme (in the presence of 50 mM KCl)
- Vmax=1 nmol/min/mg enzyme (in the presence of 200 mM KCl)
pH dependencei
Optimum pH is 7.5.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 212 | Proton donor/acceptorBy similarity | 1 | |
Binding sitei | 217 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 309 | SubstrateBy similarity | 1 | |
Binding sitei | 316 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 322 | ATPPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 153 – 155 | ATPPROSITE-ProRule annotation | 3 | |
Nucleotide bindingi | 185 – 189 | ATPPROSITE-ProRule annotation | 5 | |
Nucleotide bindingi | 242 – 244 | ATPPROSITE-ProRule annotation | 3 | |
Nucleotide bindingi | 586 – 588 | ATPPROSITE-ProRule annotation | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- D-erythro-sphingosine kinase activity Source: UniProtKB
- NAD+ kinase activity Source: InterPro
- nucleosomal histone binding Source: MGI
- sphinganine kinase activity Source: UniProtKB
- sphingosine-1-phosphate receptor activity Source: MGI
GO - Biological processi
- blood vessel development Source: MGI
- brain development Source: MGI
- cell population proliferation Source: UniProtKB
- cellular response to phorbol 13-acetate 12-myristate Source: UniProtKB
- cytokine secretion involved in immune response Source: UniProtKB
- female pregnancy Source: Ensembl
- histone H2A-K5 acetylation Source: UniProtKB
- histone H2B-K12 acetylation Source: UniProtKB
- interleukin-13 secretion Source: UniProtKB
- interleukin-6 secretion Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell growth Source: UniProtKB
- negative regulation of histone deacetylase activity Source: UniProtKB
- negative regulation of histone deacetylation Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of calcium ion import Source: UniProtKB
- positive regulation of cell population proliferation Source: MGI
- positive regulation of ceramide biosynthetic process Source: UniProtKB
- positive regulation of gene expression, epigenetic Source: UniProtKB
- positive regulation of histone H3-K9 acetylation Source: UniProtKB
- positive regulation of mast cell activation involved in immune response Source: UniProtKB
- positive regulation of mast cell degranulation Source: UniProtKB
- positive regulation of protein kinase C signaling Source: UniProtKB
- regulation of ATP biosynthetic process Source: UniProtKB
- regulation of cytochrome-c oxidase activity Source: UniProtKB
- regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- regulation of reactive oxygen species biosynthetic process Source: UniProtKB
- sphinganine-1-phosphate biosynthetic process Source: UniProtKB
- sphingosine biosynthetic process Source: MGI
- sphingosine metabolic process Source: UniProtKB
- tumor necrosis factor secretion Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.1.91 3474 |
Reactomei | R-MMU-1660661 Sphingolipid de novo biosynthesis |
SABIO-RKi | Q9JIA7 |
Chemistry databases
SwissLipidsi | SLP:000000113 |
Names & Taxonomyi
Protein namesi | Recommended name: Sphingosine kinase 2Curated (EC:2.7.1.913 Publications)Short name: SK 2 Short name: SPK 2 |
Gene namesi | Name:Sphk2Imported |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1861380 Sphk2 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Plasma membrane
- Cell membrane 1 Publication
Lysosome
- Lysosome membrane By similarity
Mitochondrion
- Mitochondrion inner membrane 2 Publications
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Other locations
- Cytoplasm 2 Publications
Note: In nucleus, is located in nucleosomes where it associates with core histone proteins such as histone 3. In apoptotic cells, colocalizes with CASP1 in cell membrane where is cleaved and released from cells in an active form.By similarity
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
- intracellular membrane-bounded organelle Source: MGI
- membrane Source: UniProtKB
- nucleosome Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endoplasmic reticulum, Lysosome, Membrane, Mitochondrion, Mitochondrion inner membrane, NucleusPathology & Biotechi
Disruption phenotypei
Mutant mice are viable, fertile and have normal longevity. They show reduced SPP levels (PubMed:16314531). Mice have decreased fat mass but increased lean mass, they display increased energy expenditure compared to wild-type. Aging mice are protected from metabolic decline and obesity. 52-week old male mutant mice have decreased weight and fat mass, and increased glucose tolerance and insulin sensitivity compared to control mice (PubMed:30593892). Double knockout for SPHK1 and SPHK2 causes embryonic lethality (PubMed:16314531). Between 11.5 dpc and 12.5 dpc embryos exhibit cranial hemorrhage and die at 13.5 dpc (PubMed:16314531). At 11.5 dpc the wall of the dorsal aorta is poorly developed and endothelial cells are severely defective in all blood vessels in the mesenchymal region of the head (PubMed:16314531). Embryos also show a neural tube defect (PubMed:16314531).2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 93 – 94 | RR → EE: Loss of nuclear location. Loss of DNA synthesis inhibition. 1 Publication | 2 | |
Mutagenesisi | 213 | G → E: Abolishes sphingosine kinase activity. Decreases apoptosis induction. Abolishes sphingosine kinase activity. No effect on endoplasmic reticulum location increase upon serum starvation. Abolishes sphingosine kinase activity and decreases apoptosis induction; when associated with A-219. 1 Publication | 1 | |
Mutagenesisi | 219 | L → A: Strongly decreases sphingosine kinase activity. Decreases apoptosis induction. No effect on endoplasmic reticulum location increase upon serum starvation. Abolishes sphingosine kinase activity and decreases apoptosis induction; when associated with E-213. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL1075305 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000181359 | 1 – 617 | Sphingosine kinase 2Add BLAST | 617 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 358 | PhosphoserineCombined sources | 1 | |
Modified residuei | 364 | PhosphoserineCombined sources | 1 | |
Modified residuei | 377 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 384 | PhosphoserineBy similarity | 1 | |
Modified residuei | 386 | PhosphoserineBy similarity | 1 | |
Modified residuei | 578 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Phosphorylated by PKD on Ser-384 and Ser-386 upon PMA treatment. Phosphorylation induces export from the nucleus to the cytoplasm. Phosphorylated by MAPK1 and MAPK2 at Thr-578, phosphorylation is induced by agonists such as EGF and PMA and increases kinase activity.By similarity
Cleaved by CASP1 in apoptotic cells. The truncated form is released from cells.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9JIA7 |
jPOSTi | Q9JIA7 |
MaxQBi | Q9JIA7 |
PaxDbi | Q9JIA7 |
PRIDEi | Q9JIA7 |
PTM databases
iPTMneti | Q9JIA7 |
PhosphoSitePlusi | Q9JIA7 |
SwissPalmi | Q9JIA7 |
Expressioni
Tissue specificityi
Expressed in heart, brain, liver, kidney and testis (PubMed:10751414). Expressed by mast cells (at protein level) (PubMed:17346996). In the substantia nigra, expressed by dopaminergic neurons (at protein level) (PubMed:25637806).3 Publications
Developmental stagei
At 10.5 dpc, expression is relatively ubiquitous with the strongest signals detected in the limb buds, eyes and branchial arches and a weaker expression in the telencephalon and spinal cord.1 Publication
Inductioni
Expressopm decreases upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is used to induce Parkinson disease in mouse model.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000057342 Expressed in 256 organ(s), highest expression level in ear vesicle |
ExpressionAtlasi | Q9JIA7 baseline and differential |
Genevisiblei | Q9JIA7 MM |
Interactioni
Subunit structurei
Interacts with histone H3.
Interacts with HDAC1, HDAC2, MBD2 and SIN3A.
Interacts with EEF1A1; the interaction enhances SPHK2 kinase activity (By similarity).
Interacts with PHB2 (PubMed:20959514).
By similarity1 PublicationBinary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
P39688 | 2 | EBI-985434,EBI-524514 |
GO - Molecular functioni
- nucleosomal histone binding Source: MGI
Protein-protein interaction databases
IntActi | Q9JIA7, 6 interactors |
MINTi | Q9JIA7 |
STRINGi | 10090.ENSMUSP00000072615 |
Chemistry databases
BindingDBi | Q9JIA7 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 143 – 290 | DAGKcPROSITE-ProRule annotationAdd BLAST | 148 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 140 | Required for binding to sulfatide and phosphoinositides and for membrane localizationBy similarityAdd BLAST | 140 | |
Regioni | 210 – 213 | Substrate bindingBy similarity | 4 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 87 – 95 | NLS1 Publication | 9 | |
Motifi | 381 – 390 | NESBy similarity | 10 |
Phylogenomic databases
eggNOGi | KOG1116 Eukaryota COG1597 LUCA |
GeneTreei | ENSGT00940000161197 |
HOGENOMi | HOG000111460 |
InParanoidi | Q9JIA7 |
KOi | K04718 |
OMAi | YVSHVTC |
OrthoDBi | 681139at2759 |
PhylomeDBi | Q9JIA7 |
TreeFami | TF354296 |
Family and domain databases
Gene3Di | 3.40.50.10330, 1 hit |
InterProi | View protein in InterPro IPR017438 ATP-NAD_kinase_N IPR001206 Diacylglycerol_kinase_cat_dom IPR016064 NAD/diacylglycerol_kinase_sf |
Pfami | View protein in Pfam PF00781 DAGK_cat, 1 hit |
SMARTi | View protein in SMART SM00046 DAGKc, 1 hit |
SUPFAMi | SSF111331 SSF111331, 1 hit |
PROSITEi | View protein in PROSITE PS50146 DAGK, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q9JIA7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAPPPLLPVA ASTPILHGEF GSYPANGPRF ALTLTTQALH IQRLRPKPEA
60 70 80 90 100
RPRDGLVSLD EVSGCGTLQS RSPEDTAAYF CIYTYPRGRR GGRRRATRTF
110 120 130 140 150
RADGATTYEE NRAEAQRWAT ALTCLLRGVP LSGDQEITPE LLPRKPRLLI
160 170 180 190 200
LVNPFGGRGL AWQRCMDHVV PMISEAGLSF NLIQTERQNH ARELVQGLSL
210 220 230 240 250
SEWEGIVTVS GDGLLYEVLN GLLDRPDWED AVRMPIGVLP CGSGNALAGA
260 270 280 290 300
VNHHGGFEQV VGVDLLLNCS LLLCRGGSHP LDLLSVTLAS GSRCFSFLSV
310 320 330 340 350
AWGFLSDVDI HSERFRALGS ARFTLGAVLG LASLHTYRGR LSYLPATTEP
360 370 380 390 400
ALPIPGHSLP RAKSELVLAP APAPAATHSP LHRSVSDLPL PLPQPALVSP
410 420 430 440 450
GSPEPLPDLS LNGGGPELTG DWGGAGDAPL SPDPLLPSSP NALKTAQLSP
460 470 480 490 500
IAEGPPEMPA SSGFLPPTHS APEASTWGPV DHLLPPLGSP LPQDWVTIEG
510 520 530 540 550
EFVLMLGILP SHLCADLMAA PHARFDDGVV HLCWVRSGIS RAALLRILLA
560 570 580 590 600
MEHGNHFSLG CPHLGYAAAR AFRLEPLTPR GLLTVDGELV EYGPIQAQVH
610
PGLATLLTGP AGQKPQA
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1B0GS43 | A0A1B0GS43_MOUSE | Sphingosine kinase 2 | Sphk2 | 131 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 252 | N → S in AAF74125 (PubMed:10751414).Curated | 1 | |
Sequence conflicti | 510 | P → T in AAF74125 (PubMed:10751414).Curated | 1 | |
Sequence conflicti | 548 | L → F in AAF74125 (PubMed:10751414).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF245448 mRNA Translation: AAF74125.1 AF415214 mRNA Translation: AAL07500.1 AK004951 mRNA Translation: BAB23694.1 BC006941 mRNA Translation: AAH06941.1 BC053737 mRNA Translation: AAH53737.1 |
CCDSi | CCDS21261.1 |
RefSeqi | NP_001166032.1, NM_001172561.1 NP_064395.2, NM_020011.5 NP_975009.1, NM_203280.3 XP_006541075.1, XM_006541012.3 XP_006541076.1, XM_006541013.3 |
Genome annotation databases
Ensembli | ENSMUST00000072836; ENSMUSP00000072615; ENSMUSG00000057342 ENSMUST00000107737; ENSMUSP00000103366; ENSMUSG00000057342 ENSMUST00000210060; ENSMUSP00000147391; ENSMUSG00000057342 |
GeneIDi | 56632 |
KEGGi | mmu:56632 |
UCSCi | uc009gwt.2 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF245448 mRNA Translation: AAF74125.1 AF415214 mRNA Translation: AAL07500.1 AK004951 mRNA Translation: BAB23694.1 BC006941 mRNA Translation: AAH06941.1 BC053737 mRNA Translation: AAH53737.1 |
CCDSi | CCDS21261.1 |
RefSeqi | NP_001166032.1, NM_001172561.1 NP_064395.2, NM_020011.5 NP_975009.1, NM_203280.3 XP_006541075.1, XM_006541012.3 XP_006541076.1, XM_006541013.3 |
3D structure databases
SMRi | Q9JIA7 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q9JIA7, 6 interactors |
MINTi | Q9JIA7 |
STRINGi | 10090.ENSMUSP00000072615 |
Chemistry databases
BindingDBi | Q9JIA7 |
ChEMBLi | CHEMBL1075305 |
SwissLipidsi | SLP:000000113 |
PTM databases
iPTMneti | Q9JIA7 |
PhosphoSitePlusi | Q9JIA7 |
SwissPalmi | Q9JIA7 |
Proteomic databases
EPDi | Q9JIA7 |
jPOSTi | Q9JIA7 |
MaxQBi | Q9JIA7 |
PaxDbi | Q9JIA7 |
PRIDEi | Q9JIA7 |
Protocols and materials databases
DNASUi | 56632 |
Genome annotation databases
Ensembli | ENSMUST00000072836; ENSMUSP00000072615; ENSMUSG00000057342 ENSMUST00000107737; ENSMUSP00000103366; ENSMUSG00000057342 ENSMUST00000210060; ENSMUSP00000147391; ENSMUSG00000057342 |
GeneIDi | 56632 |
KEGGi | mmu:56632 |
UCSCi | uc009gwt.2 mouse |
Organism-specific databases
CTDi | 56848 |
MGIi | MGI:1861380 Sphk2 |
Phylogenomic databases
eggNOGi | KOG1116 Eukaryota COG1597 LUCA |
GeneTreei | ENSGT00940000161197 |
HOGENOMi | HOG000111460 |
InParanoidi | Q9JIA7 |
KOi | K04718 |
OMAi | YVSHVTC |
OrthoDBi | 681139at2759 |
PhylomeDBi | Q9JIA7 |
TreeFami | TF354296 |
Enzyme and pathway databases
BRENDAi | 2.7.1.91 3474 |
Reactomei | R-MMU-1660661 Sphingolipid de novo biosynthesis |
SABIO-RKi | Q9JIA7 |
Miscellaneous databases
ChiTaRSi | Sphk2 mouse |
PROi | PR:Q9JIA7 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000057342 Expressed in 256 organ(s), highest expression level in ear vesicle |
ExpressionAtlasi | Q9JIA7 baseline and differential |
Genevisiblei | Q9JIA7 MM |
Family and domain databases
Gene3Di | 3.40.50.10330, 1 hit |
InterProi | View protein in InterPro IPR017438 ATP-NAD_kinase_N IPR001206 Diacylglycerol_kinase_cat_dom IPR016064 NAD/diacylglycerol_kinase_sf |
Pfami | View protein in Pfam PF00781 DAGK_cat, 1 hit |
SMARTi | View protein in SMART SM00046 DAGKc, 1 hit |
SUPFAMi | SSF111331 SSF111331, 1 hit |
PROSITEi | View protein in PROSITE PS50146 DAGK, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SPHK2_MOUSE | |
Accessioni | Q9JIA7Primary (citable) accession number: Q9JIA7 Secondary accession number(s): Q91VA9, Q9DBH6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 24, 2001 |
Last sequence update: | March 27, 2002 | |
Last modified: | October 16, 2019 | |
This is version 161 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot