ID   SGPP2_HUMAN             Reviewed;         399 AA.
AC   Q8IWX5; A3KPB4; Q8N8Q6;
DT   10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   09-APR-2025, entry version 158.
DE   RecName: Full=Sphingosine-1-phosphate phosphatase 2 {ECO:0000305};
DE            Short=SPPase2;
DE            Short=Spp2;
DE            Short=hSPP2;
DE            EC=3.1.3.- {ECO:0000269|PubMed:12411432, ECO:0000269|PubMed:27059959};
DE   AltName: Full=Sphingosine-1-phosphatase 2;
GN   Name=SGPP2 {ECO:0000312|HGNC:HGNC:19953};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP   SUBCELLULAR LOCATION, AND 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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   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).
RN   [5]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=17113265; DOI=10.1016/j.cellsig.2006.09.004;
RA   Mechtcheriakova D., Wlachos A., Sobanov J., Kopp T., Reuschel R.,
RA   Bornancin F., Cai R., Zemann B., Urtz N., Stingl G., Zlabinger G.,
RA   Woisetschlager M., Baumruker T., Billich A.;
RT   "Sphingosine 1-phosphate phosphatase 2 is induced during inflammatory
RT   responses.";
RL   Cell. Signal. 19:748-760(2007).
RN   [6]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=31916624; DOI=10.1096/fj.201902645r;
RA   Jojima K., Edagawa M., Sawai M., Ohno Y., Kihara A.;
RT   "Biosynthesis of the anti-lipid-microdomain sphingoid base 4,14-
RT   sphingadiene by the ceramide desaturase FADS3.";
RL   FASEB J. 34:3318-3335(2020).
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 (PubMed:12411432). Sphingosine-1-phosphate phosphatase activity
CC       is 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 (PubMed:17113265). Plays a role in the
CC       regulation of pancreatic islet beta-cell endoplasmic reticulum stress
CC       and proliferation (By similarity). {ECO:0000250|UniProtKB:Q810K3,
CC       ECO:0000250|UniProtKB:Q9BX95, ECO:0000269|PubMed:12411432,
CC       ECO:0000269|PubMed:17113265, ECO:0000269|PubMed:31916624}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=sphinganine 1-phosphate + H2O = sphinganine + phosphate;
CC         Xref=Rhea:RHEA:27514, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57817, ChEBI:CHEBI:57939;
CC         Evidence={ECO:0000269|PubMed:12411432};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27515;
CC         Evidence={ECO:0000269|PubMed:12411432};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=sphing-4-enine 1-phosphate + H2O = sphing-4-enine + phosphate;
CC         Xref=Rhea:RHEA:27518, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57756, ChEBI:CHEBI:60119;
CC         Evidence={ECO:0000269|PubMed:12411432, ECO:0000269|PubMed:27059959,
CC         ECO:0000269|PubMed:31916624};
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:0000269|PubMed:31916624};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33068;
CC         Evidence={ECO:0000305|PubMed:31916624};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:12411432}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:12411432}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8IWX5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IWX5-2; Sequence=VSP_039385;
CC   -!- TISSUE SPECIFICITY: Expressed strongly in kidney and heart, followed by
CC       brain, colon, small intestine and lung. Not detected in skeletal
CC       muscle, thymus, spleen, liver, placenta, and peripheral blood
CC       leukocytes. {ECO:0000269|PubMed:12411432}.
CC   -!- INDUCTION: Strongly induced by TNF, also induced by bacterial
CC       lipopolycaccharides (LPS) in neutrophils, endothelial cells, and other
CC       cell types. Not induced by growth-related factors.
CC       {ECO:0000269|PubMed:17113265}.
CC   -!- SIMILARITY: Belongs to the type 2 lipid phosphate phosphatase family.
CC       {ECO:0000305}.
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DR   EMBL; AF542512; AAN28731.1; -; mRNA.
DR   EMBL; AK096323; BAC04762.1; -; mRNA.
DR   EMBL; AK314322; BAG36970.1; -; mRNA.
DR   EMBL; BC134342; AAI34343.1; -; mRNA.
DR   CCDS; CCDS2453.1; -. [Q8IWX5-1]
DR   RefSeq; NP_001307762.1; NM_001320833.2. [Q8IWX5-2]
DR   RefSeq; NP_001307763.1; NM_001320834.2. [Q8IWX5-2]
DR   RefSeq; NP_689599.2; NM_152386.3. [Q8IWX5-1]
DR   RefSeq; XP_016858844.1; XM_017003355.1.
DR   AlphaFoldDB; Q8IWX5; -.
DR   SMR; Q8IWX5; -.
DR   BioGRID; 126231; 4.
DR   IntAct; Q8IWX5; 2.
DR   STRING; 9606.ENSP00000315137; -.
DR   SwissLipids; SLP:000000159; -.
DR   PhosphoSitePlus; Q8IWX5; -.
DR   BioMuta; SGPP2; -.
DR   DMDM; 41700844; -.
DR   jPOST; Q8IWX5; -.
DR   MassIVE; Q8IWX5; -.
DR   PaxDb; 9606-ENSP00000315137; -.
DR   PeptideAtlas; Q8IWX5; -.
DR   ProteomicsDB; 70920; -. [Q8IWX5-1]
DR   Antibodypedia; 34359; 87 antibodies from 19 providers.
DR   DNASU; 130367; -.
DR   Ensembl; ENST00000321276.8; ENSP00000315137.7; ENSG00000163082.10. [Q8IWX5-1]
DR   GeneID; 130367; -.
DR   KEGG; hsa:130367; -.
DR   MANE-Select; ENST00000321276.8; ENSP00000315137.7; NM_152386.4; NP_689599.2.
DR   UCSC; uc010zlo.3; human. [Q8IWX5-1]
DR   AGR; HGNC:19953; -.
DR   CTD; 130367; -.
DR   DisGeNET; 130367; -.
DR   GeneCards; SGPP2; -.
DR   HGNC; HGNC:19953; SGPP2.
DR   HPA; ENSG00000163082; Low tissue specificity.
DR   MIM; 612827; gene.
DR   neXtProt; NX_Q8IWX5; -.
DR   OpenTargets; ENSG00000163082; -.
DR   PharmGKB; PA134956234; -.
DR   VEuPathDB; HostDB:ENSG00000163082; -.
DR   eggNOG; KOG2822; Eukaryota.
DR   GeneTree; ENSGT00940000159500; -.
DR   HOGENOM; CLU_043042_1_0_1; -.
DR   InParanoid; Q8IWX5; -.
DR   OMA; KFMVGIV; -.
DR   OrthoDB; 301434at2759; -.
DR   PhylomeDB; Q8IWX5; -.
DR   TreeFam; TF323419; -.
DR   PathwayCommons; Q8IWX5; -.
DR   Reactome; R-HSA-9845614; Sphingolipid catabolism.
DR   BioGRID-ORCS; 130367; 11 hits in 1154 CRISPR screens.
DR   ChiTaRS; SGPP2; human.
DR   GenomeRNAi; 130367; -.
DR   Pharos; Q8IWX5; Tbio.
DR   PRO; PR:Q8IWX5; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q8IWX5; protein.
DR   Bgee; ENSG00000163082; Expressed in ileal mucosa and 166 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum 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; IDA:UniProtKB.
DR   GO; GO:0046839; P:phospholipid dephosphorylation; IBA:GO_Central.
DR   GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; ISS:UniProtKB.
DR   GO; GO:0030149; P:sphingolipid catabolic process; TAS:Reactome.
DR   GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB.
DR   CDD; cd03388; PAP2_SPPase1; 1.
DR   FunFam; 1.20.144.10:FF:000011; sphingosine-1-phosphate phosphatase 1; 1.
DR   Gene3D; 1.20.144.10; Phosphatidic acid phosphatase type 2/haloperoxidase; 1.
DR   InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR   InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR   PANTHER; PTHR14969:SF14; SPHINGOSINE-1-PHOSPHATE PHOSPHATASE 2; 1.
DR   PANTHER; PTHR14969; SPHINGOSINE-1-PHOSPHATE PHOSPHOHYDROLASE; 1.
DR   Pfam; PF01569; PAP2; 1.
DR   SMART; SM00014; acidPPc; 1.
DR   SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW   Membrane; Proteomics identification; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..399
FT                   /note="Sphingosine-1-phosphate phosphatase 2"
FT                   /id="PRO_0000114480"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        121..141
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        160..180
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        185..205
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        219..239
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        247..267
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        280..300
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        318..338
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        371..391
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          136..144
FT                   /note="Phosphatase sequence motif I"
FT                   /evidence="ECO:0000305"
FT   REGION          163..166
FT                   /note="Phosphatase sequence motif II"
FT                   /evidence="ECO:0000305"
FT   REGION          206..217
FT                   /note="Phosphatase sequence motif III"
FT                   /evidence="ECO:0000305"
FT   ACT_SITE        166
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P0A924"
FT   ACT_SITE        213
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P0A924"
FT   SITE            217
FT                   /note="Stabilizes the active site histidine for
FT                   nucleophilic attack"
FT                   /evidence="ECO:0000250|UniProtKB:P0A924"
FT   VAR_SEQ         1..128
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_039385"
SQ   SEQUENCE   399 AA;  44741 MW;  7615BA231263D0B6 CRC64;
     MAELLRSLQD SQLVARFQRR CGLFPAPDEG PRENGADPTE RAARVPGVEH LPAANGKGGE
     APANGLRRAA APEAYVQKYV VKNYFYYYLF QFSAALGQEV FYITFLPFTH WNIDPYLSRR
     LIIIWVLVMY IGQVAKDVLK WPRPSSPPVV KLEKRLIAEY GMPSTHAMAA TAIAFTLLIS
     TMDRYQYPFV LGLVMAVVFS TLVCLSRLYT GMHTVLDVLG GVLITALLIV LTYPAWTFID
     CLDSASPLFP VCVIVVPFFL CYNYPVSDYY SPTRADTTTI LAAGAGVTIG FWINHFFQLV
     SKPAESLPVI QNIPPLTTYM LVLGLTKFAV GIVLILLVRQ LVQNLSLQVL YSWFKVVTRN
     KEARRRLEIE VPYKFVTYTS VGICATTFVP MLHRFLGLP
//