SPHK1_MOUSE
ID SPHK1_MOUSE Reviewed; 382 AA.
AC Q8CI15; O88886; Q3U2E3; Q91ZN3;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Sphingosine kinase 1 {ECO:0000305};
DE Short=SK 1 {ECO:0000303|PubMed:27806293};
DE Short=SPK 1;
DE EC=2.7.1.91 {ECO:0000269|PubMed:17346996, ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:33334894};
DE AltName: Full=Acetyltransferase SPHK1 {ECO:0000303|PubMed:29662056};
DE EC=2.3.1.- {ECO:0000269|PubMed:29662056};
GN Name=Sphk1 {ECO:0000312|MGI:MGI:1316649};
GN Synonyms=Sk1 {ECO:0000303|PubMed:27806293};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, AND TISSUE SPECIFICITY.
RX PubMed=9726979; DOI=10.1074/jbc.273.37.23722;
RA Kohama T., Olivera A., Edsall L., Nagiec M.M., Dickson R., Spiegel S.;
RT "Molecular cloning and functional characterization of murine sphingosine
RT kinase.";
RL J. Biol. Chem. 273:23722-23728(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Thompson D., Pyne S.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH ACY1.
RX PubMed=15196915; DOI=10.1016/j.febslet.2004.04.093;
RA Maceyka M., Nava V.E., Milstien S., Spiegel S.;
RT "Aminoacylase 1 is a sphingosine kinase 1-interacting protein.";
RL FEBS Lett. 568:30-34(2004).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=15459201; DOI=10.1074/jbc.m406512200;
RA Allende M.L., Sasaki T., Kawai H., Olivera A., Mi Y.,
RA van Echten-Deckert G., Hajdu R., Rosenbach M., Keohane C.A., Mandala S.,
RA Spiegel S., Proia R.L.;
RT "Mice deficient in sphingosine kinase 1 are rendered lymphopenic by
RT FTY720.";
RL J. Biol. Chem. 279:52487-52492(2004).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16118219; DOI=10.1074/jbc.m502207200;
RA Maceyka M., Sankala H., Hait N.C., Le Stunff H., Liu H., Toman R.,
RA Collier C., Zhang M., Satin L.S., Merrill A.H. Jr., Milstien S.,
RA Spiegel S.;
RT "SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in
RT sphingolipid metabolism.";
RL J. Biol. Chem. 280:37118-37129(2005).
RN [9]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=16314531; DOI=10.1128/mcb.25.24.11113-11121.2005;
RA Mizugishi K., Yamashita T., Olivera A., Miller G.F., Spiegel S.,
RA Proia R.L.;
RT "Essential role for sphingosine kinases in neural and vascular
RT development.";
RL Mol. Cell. Biol. 25:11113-11121(2005).
RN [10]
RP CATALYTIC ACTIVITY.
RX PubMed=17346996; DOI=10.1016/j.immuni.2007.02.008;
RA Olivera A., Mizugishi K., Tikhonova A., Ciaccia L., Odom S., Proia R.L.,
RA Rivera J.;
RT "The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of
RT mast cell function and anaphylaxis.";
RL Immunity 26:287-297(2007).
RN [11]
RP FUNCTION.
RX PubMed=21084291; DOI=10.1074/jbc.m110.171116;
RA Hisano Y., Kobayashi N., Kawahara A., Yamaguchi A., Nishi T.;
RT "The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter
RT of the phosphorylated form of the immunomodulating agent FTY720.";
RL J. Biol. Chem. 286:1758-1766(2011).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24929359; DOI=10.1038/ncb2987;
RA Shen H., Giordano F., Wu Y., Chan J., Zhu C., Milosevic I., Wu X., Yao K.,
RA Chen B., Baumgart T., Sieburth D., De Camilli P.;
RT "Coupling between endocytosis and sphingosine kinase 1 recruitment.";
RL Nat. Cell Biol. 16:652-662(2014).
RN [13]
RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=25417698; DOI=10.1038/ncomms6514;
RA Lee H., Lee J.K., Park M.H., Hong Y.R., Marti H.H., Kim H., Okada Y.,
RA Otsu M., Seo E.J., Park J.H., Bae J.H., Okino N., He X., Schuchman E.H.,
RA Bae J.S., Jin H.K.;
RT "Pathological roles of the VEGF/SphK pathway in Niemann-Pick type C
RT neurons.";
RL Nat. Commun. 5:5514-5514(2014).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-82.
RX PubMed=27806293; DOI=10.1016/j.celrep.2016.10.019;
RA Young M.M., Takahashi Y., Fox T.E., Yun J.K., Kester M., Wang H.G.;
RT "Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic
RT Membrane Trafficking.";
RL Cell Rep. 17:1532-1545(2016).
RN [15]
RP FUNCTION.
RX PubMed=28049734; DOI=10.1074/jbc.m116.762377;
RA Lima S., Milstien S., Spiegel S.;
RT "Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane
RT Trafficking.";
RL J. Biol. Chem. 292:3074-3088(2017).
RN [16]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=29662056; DOI=10.1038/s41467-018-03674-2;
RA Lee J.Y., Han S.H., Park M.H., Baek B., Song I.S., Choi M.K., Takuwa Y.,
RA Ryu H., Kim S.H., He X., Schuchman E.H., Bae J.S., Jin H.K.;
RT "Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in a model
RT of Alzheimer's Disease.";
RL Nat. Commun. 9:1479-1479(2018).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33334894; DOI=10.1074/jbc.ra120.012941;
RA Nguyen T.Q., Vu T.M., Tukijan F., Muralidharan S., Foo J.C., Li Chin J.F.,
RA Hasan Z., Torta F., Nguyen L.N.;
RT "Erythrocytes efficiently utilize exogenous sphingosines for S1P synthesis
RT and export via Mfsd2b.";
RL J. Biol. Chem. 296:100201-100201(2021).
CC -!- FUNCTION: Catalyzes the phosphorylation of sphingosine to form
CC sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and
CC extracellular functions (PubMed:17346996, PubMed:21084291,
CC PubMed:25417698, PubMed:29662056, PubMed:33334894). Also acts on D-
CC erythro-sphingosine and to a lesser extent sphinganine, but not other
CC lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine,
CC diacylglycerol, ceramide, or phosphatidylinositol (PubMed:9726979). In
CC contrast to proapoptotic SPHK2, has a negative effect on intracellular
CC ceramide levels, enhances cell growth and inhibits apoptosis
CC (PubMed:16118219). Involved in the regulation of inflammatory response
CC and neuroinflammation. Via the product sphingosine 1-phosphate,
CC stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation
CC of NF-kappa-B in response to TNF signaling (By similarity). In response
CC to TNF and in parallel to NF-kappa-B activation, negatively regulates
CC RANTES induction through p38 MAPK signaling pathway (By similarity).
CC Involved in endocytic membrane trafficking induced by sphingosine,
CC recruited to dilate endosomes, also plays a role on later stages of
CC endosomal maturation and membrane fusion independently of its kinase
CC activity (PubMed:27806293, PubMed:28049734). In Purkinje cells, seems
CC to be also involved in the regulation of autophagosome-lysosome fusion
CC upon VEGFA (PubMed:25417698). {ECO:0000250|UniProtKB:Q9NYA1,
CC ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:21084291,
CC ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:27806293,
CC ECO:0000269|PubMed:28049734, ECO:0000269|PubMed:33334894,
CC ECO:0000269|PubMed:9726979, ECO:0000305|PubMed:29662056}.
CC -!- FUNCTION: Has serine acetyltransferase activity on PTGS2/COX2 in an
CC acetyl-CoA dependent manner. The acetyltransferase activity increases
CC in presence of the kinase substrate, sphingosine. During
CC neuroinflammation, through PTGS2 acetylation, promotes neuronal
CC secretion of specialized preresolving mediators (SPMs), especially 15-
CC R-lipoxin A4, which results in an increase of phagocytic microglia.
CC {ECO:0000269|PubMed:29662056}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:51496, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:76941, ChEBI:CHEBI:84410, ChEBI:CHEBI:456216;
CC EC=2.7.1.91; Evidence={ECO:0000269|PubMed:17346996,
CC ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:29662056,
CC ECO:0000269|PubMed:33334894};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51497;
CC Evidence={ECO:0000269|PubMed:17346996, ECO:0000269|PubMed:25417698,
CC ECO:0000269|PubMed:29662056, ECO:0000269|PubMed:33334894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-seryl-[protein] = CoA + O-acetyl-L-seryl-
CC [protein]; Xref=Rhea:RHEA:59392, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:15352, ChEBI:CHEBI:29999, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:141128; Evidence={ECO:0000269|PubMed:29662056};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59393;
CC Evidence={ECO:0000269|PubMed:29662056};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + sphinganine = ADP + H(+) + sphinganine 1-phosphate;
CC Xref=Rhea:RHEA:15465, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:57939, ChEBI:CHEBI:456216;
CC EC=2.7.1.91; Evidence={ECO:0000269|PubMed:9726979};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + sphing-4-enine = ADP + H(+) + sphing-4-enine 1-
CC phosphate; Xref=Rhea:RHEA:35847, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57756, ChEBI:CHEBI:60119,
CC ChEBI:CHEBI:456216; EC=2.7.1.91;
CC Evidence={ECO:0000269|PubMed:9726979};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-amino-sn-glycerol + ATP = 1-O-hexadecyl-2-
CC desoxy-2-amino-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:41163, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77786, ChEBI:CHEBI:77787, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9NYA1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NYA1};
CC -!- ACTIVITY REGULATION: Acetyltransferase activity increases in presence
CC of the kinase substrate, sphingosine (PubMed:29662056). In Purkinje
CC cells, kinase activity on sphingosine increases in presence of VEGFA
CC (PubMed:25417698). In neurons, kinase activity increases during the
CC first 24h in presence of Amyloid-beta protein 42 to decrease after 96h
CC (By similarity). {ECO:0000250|UniProtKB:Q91V26,
CC ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:29662056}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=60.2 uM for Acetyl-CoA (in presence of 10 uM of sphingosine)
CC {ECO:0000269|PubMed:29662056};
CC KM=6.4 uM for Acetyl-CoA (in presence of 100 uM of sphingosine)
CC {ECO:0000269|PubMed:29662056};
CC Note=kcat is 0.0185 min(-1) for Acetyl-CoA as substrate.
CC {ECO:0000269|PubMed:29662056};
CC -!- SUBUNIT: Interacts with ACY1 (PubMed:15196915). Binds to calmodulin.
CC Interacts with SPHKAP (By similarity). Interacts with CIB1, the
CC interaction occurs in a calcium-dependent manner (By similarity).
CC Interacts with TRAF2 (By similarity). Interacts with EEF1A1; the
CC interaction enhances SPHK1 kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9NYA1, ECO:0000269|PubMed:15196915}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16118219,
CC ECO:0000269|PubMed:27806293, ECO:0000269|PubMed:29662056}. Endosome
CC membrane {ECO:0000269|PubMed:24929359, ECO:0000269|PubMed:27806293};
CC Peripheral membrane protein {ECO:0000269|PubMed:24929359}. Nucleus
CC {ECO:0000269|PubMed:29662056}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9NYA1}. Synapse {ECO:0000269|PubMed:24929359}.
CC Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-
CC dependent manner. Binds to membranes containing negatively charged
CC lipids but not neutral lipids (By similarity). Recruited to endocytic
CC membranes by sphingosine where promotes membrane fusion
CC (PubMed:27806293). {ECO:0000250|UniProtKB:Q9NYA1,
CC ECO:0000269|PubMed:27806293}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8CI15-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CI15-2; Sequence=VSP_033448;
CC Name=3;
CC IsoId=Q8CI15-3; Sequence=VSP_033449;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9726979). Expressed in
CC brain (at protein level). Detected in neurons.
CC {ECO:0000269|PubMed:29662056, ECO:0000269|PubMed:9726979}.
CC -!- DEVELOPMENTAL STAGE: At 10.5 dpc, expressed in the whole brain, with
CC the highest levels in the telencephalon. {ECO:0000269|PubMed:16314531}.
CC -!- DISRUPTION PHENOTYPE: Mutants are viable, fertile and without any
CC obvious abnormalities (PubMed:15459201). Mutant mice show reduced SPP
CC levels in serum (PubMed:16314531, PubMed:15459201). Conditional mutants
CC in neurons exhibit a decrease of amyloid-beta phagocytic activity
CC (PubMed:29662056). Double knockout for SPHK1 and SPHK2 causes embryonic
CC lethality (PubMed:16314531). Between 11.5 dpc and 12.5 dpc embryos
CC exhibit cranial hemorrhage and die at 13.5 dpc (PubMed:16314531). At
CC 11.5 dpc the wall of the dorsal aorta is poorly developed and
CC endothelial cells are severely defective in all blood vessels in the
CC mesenchymal region of the head (PubMed:16314531). Double knockout
CC embryos also show a neural tube deffect (PubMed:16314531).
CC {ECO:0000269|PubMed:15459201, ECO:0000269|PubMed:16314531,
CC ECO:0000269|PubMed:29662056}.
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DR EMBL; AF068749; AAC61698.1; -; mRNA.
DR EMBL; AF415213; AAL07499.1; -; mRNA.
DR EMBL; AK155332; BAE33198.1; -; mRNA.
DR EMBL; AK160900; BAE36079.1; -; mRNA.
DR EMBL; AL645851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037710; AAH37710.1; -; mRNA.
DR CCDS; CCDS25668.1; -. [Q8CI15-1]
DR CCDS; CCDS48986.1; -. [Q8CI15-3]
DR RefSeq; NP_001165943.1; NM_001172472.1. [Q8CI15-1]
DR RefSeq; NP_001165944.1; NM_001172473.1. [Q8CI15-1]
DR RefSeq; NP_001165946.1; NM_001172475.1. [Q8CI15-3]
DR RefSeq; NP_035581.1; NM_011451.3.
DR RefSeq; NP_079643.2; NM_025367.6. [Q8CI15-1]
DR RefSeq; XP_006532733.1; XM_006532670.3.
DR RefSeq; XP_006532734.1; XM_006532671.3.
DR RefSeq; XP_006532735.1; XM_006532672.3. [Q8CI15-3]
DR RefSeq; XP_006532736.1; XM_006532673.3.
DR AlphaFoldDB; Q8CI15; -.
DR SMR; Q8CI15; -.
DR IntAct; Q8CI15; 3.
DR STRING; 10090.ENSMUSP00000131010; -.
DR BindingDB; Q8CI15; -.
DR ChEMBL; CHEMBL2401605; -.
DR SwissLipids; SLP:000000114; -.
DR iPTMnet; Q8CI15; -.
DR PhosphoSitePlus; Q8CI15; -.
DR MaxQB; Q8CI15; -.
DR PaxDb; Q8CI15; -.
DR PRIDE; Q8CI15; -.
DR ProteomicsDB; 257558; -. [Q8CI15-1]
DR ProteomicsDB; 257559; -. [Q8CI15-2]
DR ProteomicsDB; 258584; -. [Q8CI15-3]
DR Antibodypedia; 19687; 754 antibodies from 48 providers.
DR DNASU; 20698; -.
DR Ensembl; ENSMUST00000063396; ENSMUSP00000064743; ENSMUSG00000061878. [Q8CI15-1]
DR Ensembl; ENSMUST00000063446; ENSMUSP00000067865; ENSMUSG00000061878. [Q8CI15-1]
DR Ensembl; ENSMUST00000100201; ENSMUSP00000097775; ENSMUSG00000061878. [Q8CI15-3]
DR Ensembl; ENSMUST00000106386; ENSMUSP00000101994; ENSMUSG00000061878. [Q8CI15-1]
DR Ensembl; ENSMUST00000106387; ENSMUSP00000101995; ENSMUSG00000061878. [Q8CI15-1]
DR Ensembl; ENSMUST00000106388; ENSMUSP00000101996; ENSMUSG00000061878. [Q8CI15-1]
DR Ensembl; ENSMUST00000141798; ENSMUSP00000131010; ENSMUSG00000061878. [Q8CI15-2]
DR GeneID; 20698; -.
DR KEGG; mmu:20698; -.
DR UCSC; uc007mlg.2; mouse. [Q8CI15-3]
DR UCSC; uc007mlh.2; mouse. [Q8CI15-1]
DR UCSC; uc007mll.2; mouse. [Q8CI15-2]
DR CTD; 8877; -.
DR MGI; MGI:1316649; Sphk1.
DR VEuPathDB; HostDB:ENSMUSG00000061878; -.
DR eggNOG; KOG1116; Eukaryota.
DR GeneTree; ENSGT00940000157864; -.
DR InParanoid; Q8CI15; -.
DR OMA; AECDLGT; -.
DR OrthoDB; 681139at2759; -.
DR PhylomeDB; Q8CI15; -.
DR TreeFam; TF354296; -.
DR BRENDA; 2.7.1.91; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-MMU-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR SABIO-RK; Q8CI15; -.
DR BioGRID-ORCS; 20698; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Sphk1; mouse.
DR PRO; PR:Q8CI15; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8CI15; protein.
DR Bgee; ENSMUSG00000061878; Expressed in gastrula and 144 other tissues.
DR ExpressionAtlas; Q8CI15; baseline and differential.
DR Genevisible; Q8CI15; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0016407; F:acetyltransferase activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0017050; F:D-erythro-sphingosine kinase activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR GO; GO:0001727; F:lipid kinase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0008481; F:sphinganine kinase activity; IDA:UniProtKB.
DR GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; ISO:MGI.
DR GO; GO:0001568; P:blood vessel development; IGI:MGI.
DR GO; GO:0007420; P:brain development; IGI:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0019371; P:cyclooxygenase pathway; ISO:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1900060; P:negative regulation of ceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IGI:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISO:MGI.
DR GO; GO:0006473; P:protein acetylation; IMP:UniProtKB.
DR GO; GO:0030100; P:regulation of endocytosis; IMP:UniProtKB.
DR GO; GO:1905364; P:regulation of endosomal vesicle fusion; IMP:UniProtKB.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; IMP:MGI.
DR GO; GO:1903978; P:regulation of microglial cell activation; IMP:UniProtKB.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0090520; P:sphingolipid mediated signaling pathway; IDA:MGI.
DR GO; GO:0006665; P:sphingolipid metabolic process; IBA:GO_Central.
DR GO; GO:0046512; P:sphingosine biosynthetic process; ISO:MGI.
DR GO; GO:0006670; P:sphingosine metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calmodulin-binding; Cell membrane;
KW Cytoplasm; Endosome; Kinase; Lipid metabolism; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Synapse;
KW Transferase.
FT CHAIN 1..382
FT /note="Sphingosine kinase 1"
FT /id="PRO_0000333032"
FT DOMAIN 12..159
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT MOTIF 147..155
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT MOTIF 161..169
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT ACT_SITE 81
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 22..24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 54..58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 79..82
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 111..113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 178
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 191
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 340..342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT MOD_RES 193
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT VAR_SEQ 1..3
FT /note="MEP -> MWWCCVLFV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9726979"
FT /id="VSP_033448"
FT VAR_SEQ 4
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_033449"
FT MUTAGEN 82
FT /note="G->D: No effect on recruitment to endocytic
FT membrane. No effect on membrane fusion produced by
FT sphingosine."
FT /evidence="ECO:0000269|PubMed:27806293"
FT CONFLICT 146
FT /note="R -> H (in Ref. 1; BAE33198)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 42443 MW; B791FAA58FCE3D29 CRC64;
MEPVECPRGL LPRPCRVLVL LNPQGGKGKA LQLFQSRVQP FLEEAEITFK LILTERKNHA
RELVCAEELG HWDALAVMSG DGLMHEVVNG LMERPDWETA IQKPLCSLPG GSGNALAASV
NHYAGYEQVT NEDLLINCTL LLCRRRLSPM NLLSLHTASG LRLYSVLSLS WGFVADVDLE
SEKYRRLGEI RFTVGTFFRL ASLRIYQGQL AYLPVGTVAS KRPASTLVQK GPVDTHLVPL
EEPVPSHWTV VPEQDFVLVL VLLHTHLSSE LFAAPMGRCE AGVMHLFYVR AGVSRAALLR
LFLAMQKGKH MELDCPYLVH VPVVAFRLEP RSQRGVFSVD GELMVCEAVQ GQVHPNYLWM
VCGSRDAPSG RDSRRGPPPE EP
