SGPP1_MOUSE
ID SGPP1_MOUSE Reviewed; 430 AA.
AC Q9JI99;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Sphingosine-1-phosphate phosphatase 1 {ECO:0000305};
DE Short=SPP;
DE Short=SPPase1;
DE Short=mSPP1;
DE EC=3.1.3.- {ECO:0000269|PubMed:12411432};
DE AltName: Full=Sphingosine-1-phosphatase 1;
GN Name=Sgpp1 {ECO:0000312|MGI:MGI:2135760};
GN Synonyms=Spp1 {ECO:0000303|PubMed:23637227}, Spph1;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10859351; DOI=10.1073/pnas.120146897;
RA Mandala S.M., Thornton R., Galve-Roperh I., Poulton S., Peterson C.,
RA Olivera A., Bergstrom J., Kurtz M.B., Spiegel S.;
RT "Molecular cloning and characterization of a lipid phosphohydrolase that
RT degrades sphingosine-1-phosphate and induces cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7859-7864(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Thompson D., Pyne S.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary cancer;
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 [4]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=11756451; DOI=10.1074/jbc.m109968200;
RA Le Stunff H., Peterson C., Thornton R., Milstien S., Mandala S.M.,
RA Spiegel S.;
RT "Characterization of murine sphingosine-1-phosphate phosphohydrolase.";
RL J. Biol. Chem. 277:8920-8927(2002).
RN [5]
RP CATALYTIC ACTIVITY.
RX PubMed=12411432; DOI=10.1074/jbc.m209514200;
RA Ogawa C., Kihara A., Gokoh M., Igarashi Y.;
RT "Identification and characterization of a novel human sphingosine-1-
RT phosphate phosphohydrolase, hSPP2.";
RL J. Biol. Chem. 278:1268-1272(2003).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12235122; DOI=10.1083/jcb.200203123;
RA Le Stunff H., Galve-Roperh I., Peterson C., Milstien S., Spiegel S.;
RT "Sphingosine-1-phosphate phosphohydrolase in regulation of sphingolipid
RT metabolism and apoptosis.";
RL J. Cell Biol. 158:1039-1049(2002).
RN [7]
RP FUNCTION.
RX PubMed=17895250; DOI=10.1074/jbc.m703329200;
RA Le Stunff H., Giussani P., Maceyka M., Lepine S., Milstien S., Spiegel S.;
RT "Recycling of sphingosine is regulated by the concerted actions of
RT sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2.";
RL J. Biol. Chem. 282:34372-34380(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23637227; DOI=10.1074/jbc.m113.478420;
RA Allende M.L., Sipe L.M., Tuymetova G., Wilson-Henjum K.L., Chen W.,
RA Proia R.L.;
RT "Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte
RT differentiation and epidermal homeostasis.";
RL J. Biol. Chem. 288:18381-18391(2013).
CC -!- FUNCTION: Specifically dephosphorylates sphingosine 1-phosphate (S1P),
CC dihydro-S1P, and phyto-S1P (PubMed:10859351, PubMed:11756451). Does not
CC act on ceramide 1-phosphate, lysophosphatidic acid or phosphatidic
CC acid. Sphingosine-1-phosphate phosphatase activity is needed for
CC efficient recycling of sphingosine into the sphingolipid synthesis
CC pathway. Regulates the intracellular levels of the bioactive
CC sphingolipid metabolite S1P that regulates diverse biological processes
CC acting both as an extracellular receptor ligand or as an intracellular
CC second messenger (PubMed:10859351, Ref.2). Involved in efficient
CC ceramide synthesis from exogenous sphingoid bases. Converts S1P to
CC sphingosine, which is readily metabolized to ceramide via ceramide
CC synthase (PubMed:12235122, PubMed:17895250). In concert with
CC sphingosine kinase 2 (SphK2), recycles sphingosine into ceramide
CC through a phosphorylation/dephosphorylation cycle (PubMed:17895250).
CC Regulates endoplasmic-to-Golgi trafficking of ceramides, resulting in
CC the regulation of ceramide levels in the endoplasmic reticulum,
CC preferentially long-chain ceramide species, and influences the
CC anterograde membrane transport of both ceramide and proteins from the
CC endoplasmic reticulum to the Golgi apparatus (By similarity). The
CC modulation of intracellular ceramide levels in turn regulates apoptosis
CC (PubMed:12235122). Via S1P levels, modulates resting tone,
CC intracellular Ca(2+) and myogenic vasoconstriction in resistance
CC arteries. Also involved in unfolded protein response (UPR) and ER
CC stress-induced autophagy via regulation of intracellular S1P levels (By
CC similarity). Involved in the regulation of epidermal homeostasis and
CC keratinocyte differentiation (PubMed:23637227).
CC {ECO:0000250|UniProtKB:Q9BX95, ECO:0000269|PubMed:10859351,
CC ECO:0000269|PubMed:11756451, ECO:0000269|PubMed:12235122,
CC ECO:0000269|PubMed:17895250, ECO:0000269|PubMed:23637227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphinganine 1-phosphate = phosphate + sphinganine;
CC Xref=Rhea:RHEA:27514, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:57939;
CC Evidence={ECO:0000269|PubMed:11756451, ECO:0000269|PubMed:12411432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27515;
CC Evidence={ECO:0000269|PubMed:11756451, ECO:0000269|PubMed:12411432};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphing-4-enine 1-phosphate = phosphate + sphing-4-enine;
CC Xref=Rhea:RHEA:27518, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:60119;
CC Evidence={ECO:0000269|PubMed:11756451};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000269|PubMed:11756451};
CC -!- ACTIVITY REGULATION: Inhibited by NaF, sodium orthovanadate,
CC propanolol, and N-ethylmaleimide. {ECO:0000269|PubMed:11756451}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=38.5 uM for sphingosine 1-phosphate {ECO:0000269|PubMed:11756451};
CC Vmax=36.4 nmol/min/mg enzyme for sphingosine 1-phosphate
CC {ECO:0000269|PubMed:11756451};
CC pH dependence:
CC Optimum pH is 6-7.5. {ECO:0000269|PubMed:11756451};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12235122}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:12235122}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Mainly found in intracellular
CC membrane fractions. {ECO:0000269|PubMed:12235122}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and kidney. Expressed in
CC epidermis, in the stratum granulosum and the stratum spinosum
CC (PubMed:23637227). {ECO:0000269|PubMed:10859351,
CC ECO:0000269|PubMed:23637227}.
CC -!- DISRUPTION PHENOTYPE: Mutants appear normal at birth, but during the
CC first week of life they exhibit stunted growth and suffer desquamation,
CC with most dying before weaning (PubMed:23637227). Their subcorneal
CC layers, including the stratum granulosum, stratum spinosum, and stratum
CC basale, are significantly thicker, whereas the stratum corneum is
CC thinner than in wild-type mic (PubMed:23637227).
CC {ECO:0000269|PubMed:23637227}.
CC -!- SIMILARITY: Belongs to the type 2 lipid phosphate phosphatase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF247177; AAF90052.1; -; mRNA.
DR EMBL; AF415215; AAL07501.1; -; mRNA.
DR EMBL; BC037592; AAH37592.1; -; mRNA.
DR CCDS; CCDS25986.1; -.
DR RefSeq; NP_109675.1; NM_030750.3.
DR AlphaFoldDB; Q9JI99; -.
DR BioGRID; 219882; 1.
DR STRING; 10090.ENSMUSP00000021450; -.
DR SwissLipids; SLP:000000381; -.
DR iPTMnet; Q9JI99; -.
DR PhosphoSitePlus; Q9JI99; -.
DR EPD; Q9JI99; -.
DR jPOST; Q9JI99; -.
DR MaxQB; Q9JI99; -.
DR PaxDb; Q9JI99; -.
DR PRIDE; Q9JI99; -.
DR ProteomicsDB; 261206; -.
DR Antibodypedia; 47291; 96 antibodies from 17 providers.
DR DNASU; 81535; -.
DR Ensembl; ENSMUST00000021450; ENSMUSP00000021450; ENSMUSG00000021054.
DR GeneID; 81535; -.
DR KEGG; mmu:81535; -.
DR UCSC; uc007nxk.2; mouse.
DR CTD; 81537; -.
DR MGI; MGI:2135760; Sgpp1.
DR VEuPathDB; HostDB:ENSMUSG00000021054; -.
DR eggNOG; KOG2822; Eukaryota.
DR GeneTree; ENSGT00940000158836; -.
DR HOGENOM; CLU_043042_1_0_1; -.
DR InParanoid; Q9JI99; -.
DR OMA; HYLQDPH; -.
DR OrthoDB; 721150at2759; -.
DR PhylomeDB; Q9JI99; -.
DR TreeFam; TF323419; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 81535; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Sgpp1; mouse.
DR PRO; PR:Q9JI99; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9JI99; protein.
DR Bgee; ENSMUSG00000021054; Expressed in seminal vesicle and 261 other tissues.
DR ExpressionAtlas; Q9JI99; baseline and differential.
DR Genevisible; Q9JI99; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070780; F:dihydrosphingosine-1-phosphate phosphatase activity; IEA:RHEA.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; IDA:MGI.
DR GO; GO:0035621; P:ER to Golgi ceramide transport; ISS:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IBA:GO_Central.
DR GO; GO:0045682; P:regulation of epidermis development; IMP:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0006668; P:sphinganine-1-phosphate metabolic process; IDA:MGI.
DR GO; GO:0006665; P:sphingolipid metabolic process; IDA:MGI.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA:MGI.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..430
FT /note="Sphingosine-1-phosphate phosphatase 1"
FT /id="PRO_0000114478"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 34..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 167..175
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000305"
FT REGION 194..197
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000305"
FT REGION 237..248
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000305"
FT COMPBIAS 40..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 197
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT ACT_SITE 244
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT SITE 248
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 103
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BX95"
SQ SEQUENCE 430 AA; 47744 MW; 503A6D8162C141C7 CRC64;
MSLGQRLALL ASRLQEPQRV ASFQRLCGVE VPLSSPAADE DAETEVRGAP GEPRRRGRQP
GAEDSPAKAD CCGAPNGVRN GLAAEPGPTG PRRAGSQRRN SLTGEEGELV KVSNLPLYYL
FCLGTELGNE LFYILFFPFW IWNLDPFVGR RLVIIWVLVM YLGQCTKDII RWPRPASPPV
IKLEVFYNSE YSMPSTHAMS GTAIPIAMFL LTYGRWQYPL IYGLILIPCW SSLVCLSRIY
MGMHSILDVI AGFLYTILIL IIFYPLVDLI DNFNQTYKYA PLIIIGLHLI LGIFSFTLDT
WSTSRGDTAE ILGSGAGIAC GSHAAYTLGL SLEPSLHMLP LAIPPLTVTL FGKAILRIVL
GMLLVLFVRD IMKKITIPLA CKLSSIPCHD IRQARQHMEV ELPYRYITYG MVGFSITFLV
PYVFSFIGIS
