SGPP2_HUMAN
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 03-AUG-2022, entry version 144.
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=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:12411432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27515;
CC Evidence={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: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_001320833.1. [Q8IWX5-2]
DR RefSeq; NP_001307763.1; NM_001320834.1. [Q8IWX5-2]
DR RefSeq; NP_689599.2; NM_152386.3. [Q8IWX5-1]
DR RefSeq; XP_016858844.1; XM_017003355.1. [Q8IWX5-2]
DR AlphaFoldDB; Q8IWX5; -.
DR SMR; Q8IWX5; -.
DR BioGRID; 126231; 4.
DR STRING; 9606.ENSP00000315137; -.
DR SwissLipids; SLP:000000159; -.
DR PhosphoSitePlus; Q8IWX5; -.
DR BioMuta; SGPP2; -.
DR DMDM; 41700844; -.
DR EPD; Q8IWX5; -.
DR MassIVE; Q8IWX5; -.
DR PaxDb; Q8IWX5; -.
DR PeptideAtlas; Q8IWX5; -.
DR PRIDE; Q8IWX5; -.
DR ProteomicsDB; 70920; -. [Q8IWX5-1]
DR Antibodypedia; 34359; 83 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 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; WVLVMYV; -.
DR OrthoDB; 721150at2759; -.
DR PhylomeDB; Q8IWX5; -.
DR TreeFam; TF323419; -.
DR PathwayCommons; Q8IWX5; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 130367; 11 hits in 1065 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 165 other tissues.
DR Genevisible; Q8IWX5; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
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; TAS:Reactome.
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:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB.
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 Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW Membrane; Reference proteome; Transmembrane; 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
