SGPP2_MOUSE
ID SGPP2_MOUSE Reviewed; 354 AA.
AC Q810K3; B2RWL5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Sphingosine-1-phosphate phosphatase 2 {ECO:0000305};
DE Short=SPPase2;
DE Short=Spp2;
DE EC=3.1.3.- {ECO:0000269|PubMed:27059959};
DE AltName: Full=Sphingosine-1-phosphatase 2;
GN Name=Sgpp2 {ECO:0000312|MGI:MGI:3589109};
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 [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Brain, and Colon;
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 [2]
RP DEVELOPMENTAL STAGE.
RC STRAIN=CD-1;
RX PubMed=19073640; DOI=10.1152/ajprenal.90232.2008;
RA Kirby R.J., Jin Y., Fu J., Cubillos J., Swertfeger D., Arend L.J.;
RT "Dynamic regulation of sphingosine-1-phosphate homeostasis during
RT development of mouse metanephric kidney.";
RL Am. J. Physiol. 296:F634-F641(2009).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=27059959; DOI=10.1074/jbc.m116.728170;
RA Taguchi Y., Allende M.L., Mizukami H., Cook E.K., Gavrilova O.,
RA Tuymetova G., Clarke B.A., Chen W., Olivera A., Proia R.L.;
RT "Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet beta-Cell
RT Endoplasmic Reticulum Stress and Proliferation.";
RL J. Biol. Chem. 291:12029-12038(2016).
CC -!- FUNCTION: Has specific phosphohydrolase activity towards sphingoid base
CC 1-phosphates. Has high phosphohydrolase activity against
CC dihydrosphingosine-1-phosphate and sphingosine-1-phosphate (S1P) in
CC vitro (Probable). Sphingosine-1-phosphate phosphatase activity is
CC needed for efficient recycling of sphingosine into the sphingolipid
CC synthesis pathway (By similarity). May play a role in attenuating
CC intracellular sphingosine 1-phosphate (S1P) signaling. May play a role
CC in pro-inflammatory signaling (By similarity). Plays a role in the
CC regulation of pancreatic islet beta-cell endoplasmic reticulum stress
CC and proliferation (PubMed:27059959). {ECO:0000250|UniProtKB:Q8IWX5,
CC ECO:0000250|UniProtKB:Q9BX95, ECO:0000269|PubMed:27059959,
CC ECO:0000305|PubMed:27059959}.
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:0000250|UniProtKB:Q8IWX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27515;
CC Evidence={ECO:0000250|UniProtKB:Q8IWX5};
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:27059959};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000269|PubMed:27059959};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-hydroxysphinganine 1-phosphate + H2O = (4R)-
CC hydroxysphinganine + phosphate; Xref=Rhea:RHEA:33067,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:64124,
CC ChEBI:CHEBI:64795; Evidence={ECO:0000250|UniProtKB:Q8IWX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33068;
CC Evidence={ECO:0000250|UniProtKB:Q8IWX5};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8IWX5}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8IWX5}.
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreatic islets. Expressed in
CC lung, small interstince, colon, kideny and brain.
CC {ECO:0000269|PubMed:27059959}.
CC -!- DEVELOPMENTAL STAGE: Developmentally regulated. Expression during
CC kidney development increases around 8 fold from 11.5 dpc and adult.
CC Highest expression is found in the ureteric bud.
CC {ECO:0000269|PubMed:19073640}.
CC -!- DISRUPTION PHENOTYPE: Mutans are viable into the adulthod. They exhibit
CC smaller pancreatic islets, defective beta-cell proliferation and
CC decreased blood insulin levels after treatment with a high-fat diet
CC (PubMed:27059959). Beta-cells show increased expression of proteins
CC characteristic of the endoplasmic reticulum stress response
CC (PubMed:27059959). {ECO:0000269|PubMed:27059959}.
CC -!- SIMILARITY: Belongs to the type 2 lipid phosphate phosphatase family.
CC {ECO:0000305}.
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DR EMBL; BC049995; AAH49995.1; -; mRNA.
DR EMBL; BC147843; AAI47844.1; -; mRNA.
DR EMBL; BC147850; AAI47851.1; -; mRNA.
DR CCDS; CCDS15083.1; -.
DR RefSeq; NP_001004173.1; NM_001004173.2.
DR AlphaFoldDB; Q810K3; -.
DR SMR; Q810K3; -.
DR STRING; 10090.ENSMUSP00000036656; -.
DR iPTMnet; Q810K3; -.
DR PhosphoSitePlus; Q810K3; -.
DR PaxDb; Q810K3; -.
DR PRIDE; Q810K3; -.
DR ProteomicsDB; 261014; -.
DR Antibodypedia; 34359; 83 antibodies from 19 providers.
DR DNASU; 433323; -.
DR Ensembl; ENSMUST00000036172; ENSMUSP00000036656; ENSMUSG00000032908.
DR GeneID; 433323; -.
DR KEGG; mmu:433323; -.
DR UCSC; uc007bqe.1; mouse.
DR CTD; 130367; -.
DR MGI; MGI:3589109; Sgpp2.
DR VEuPathDB; HostDB:ENSMUSG00000032908; -.
DR eggNOG; KOG2822; Eukaryota.
DR GeneTree; ENSGT00940000159500; -.
DR HOGENOM; CLU_043042_1_0_1; -.
DR InParanoid; Q810K3; -.
DR OMA; WVLVMYV; -.
DR OrthoDB; 721150at2759; -.
DR PhylomeDB; Q810K3; -.
DR TreeFam; TF323419; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 433323; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Sgpp2; mouse.
DR PRO; PR:Q810K3; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q810K3; protein.
DR Bgee; ENSMUSG00000032908; Expressed in epithelium of small intestine and 142 other tissues.
DR Genevisible; Q810K3; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO: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; IBA:GO_Central.
DR GO; GO:0070780; F:dihydrosphingosine-1-phosphate phosphatase activity; IEA:RHEA.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; IMP:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IBA:GO_Central.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IMP:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; ISO: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 Endoplasmic reticulum; Hydrolase; Lipid metabolism; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..354
FT /note="Sphingosine-1-phosphate phosphatase 2"
FT /id="PRO_0000114481"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..255
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 91..99
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000305"
FT REGION 118..121
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000305"
FT REGION 161..172
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000305"
FT ACT_SITE 121
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT ACT_SITE 168
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT SITE 172
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
SQ SEQUENCE 354 AA; 40248 MW; 974EB6EC6B01BEDF CRC64;
MAELLRSLRD SQLVARFQRR CGLFPAREAS GEEHVVKNYF YYYLFRFSAA LGQEVFYITF
LPFTHWNIDP NLSRRLVVIW VLVMYIGQVA KDILKWPRPS FPPVVRLEKR IIAEYGMPST
HAMAATAISF TLLISTMDRY QYPFILGLMM AVVFSTLVCL SRLYTGMHTV LDILGGVLIT
AVLIALTYPA WTLIDSLDSA SPLFPVCVIV VPFLLCYNYP VSDYYSPTRA DTTTIVAAGA
GVTLGFWINH FFQLVSKPTP SLPVIQNIPP LTTDMLVLGL TKFMVGIMLI LLVRQLVQKL
SLQVLFSWFK VVTRNKEARR RLEIEVPYKF VTYTSVGICA TTFVPMLHRF LGLL
