SGPL1_HUMAN
ID SGPL1_HUMAN Reviewed; 568 AA.
AC O95470; B2RBD4; Q7Z732; Q9ULG8; Q9UN89;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Sphingosine-1-phosphate lyase 1 {ECO:0000305};
DE Short=S1PL {ECO:0000305};
DE Short=SP-lyase 1 {ECO:0000305};
DE Short=SPL 1 {ECO:0000305};
DE Short=hSPL;
DE EC=4.1.2.27 {ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:22784711, ECO:0000269|PubMed:24809814, ECO:0000269|PubMed:28165339};
DE AltName: Full=Sphingosine-1-phosphate aldolase;
GN Name=SGPL1 {ECO:0000312|HGNC:HGNC:10817};
GN Synonyms=KIAA1252 {ECO:0000303|PubMed:10574462};
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], CATALYTIC ACTIVITY, PATHWAY, FUNCTION,
RP MUTAGENESIS OF CYS-218 AND CYS-317, AND TISSUE SPECIFICITY.
RX PubMed=11018465; DOI=10.1016/s1388-1981(00)00079-2;
RA Van Veldhoven P.P., Gijsbers S., Mannaerts G.P., Vermeesch J.R., Brys V.;
RT "Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression
RT studies and mapping to chromosome 10q22.";
RL Biochim. Biophys. Acta 1487:128-134(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF LYS-353.
RX PubMed=14570870; DOI=10.1074/jbc.m309646200;
RA Reiss U., Oskouian B., Zhou J., Gupta V., Sooriyakumaran P., Kelly S.,
RA Wang E., Merrill A.H. Jr., Saba J.D.;
RT "Sphingosine-phosphate lyase enhances stress-induced ceramide generation
RT and apoptosis.";
RL J. Biol. Chem. 279:1281-1290(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-356 AND TYR-366, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary adenoma;
RX PubMed=16777052; DOI=10.1016/j.ab.2006.05.024;
RA Zhan X., Desiderio D.M.;
RT "Nitroproteins from a human pituitary adenoma tissue discovered with a
RT nitrotyrosine affinity column and tandem mass spectrometry.";
RL Anal. Biochem. 354:279-289(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-353, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP CATALYTIC ACTIVITY.
RX PubMed=22784711; DOI=10.1158/1535-7163.mct-12-0227;
RA Brizuela L., Ader I., Mazerolles C., Bocquet M., Malavaud B., Cuvillier O.;
RT "First evidence of sphingosine 1-phosphate lyase protein expression and
RT activity downregulation in human neoplasm: implication for resistance to
RT therapeutics in prostate cancer.";
RL Mol. Cancer Ther. 11:1841-1851(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-568 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE AND SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY, PATHWAY, FUNCTION,
RP COFACTOR, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24809814; DOI=10.1021/jm500338n;
RA Weiler S., Braendlin N., Beerli C., Bergsdorf C., Schubart A., Srinivas H.,
RA Oberhauser B., Billich A.;
RT "Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-
RT yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate
RT lyase for the treatment of multiple sclerosis.";
RL J. Med. Chem. 57:5074-5084(2014).
RN [15]
RP INVOLVEMENT IN NPHS14, AND VARIANT NPHS14 505-ARG--HIS-568 DEL.
RX PubMed=28181337; DOI=10.1002/humu.23192;
RA Janecke A.R., Xu R., Steichen-Gersdorf E., Waldegger S., Entenmann A.,
RA Giner T., Krainer I., Huber L.A., Hess M.W., Frishberg Y., Barash H.,
RA Tzur S., Schreyer-Shafir N., Sukenik-Halevy R., Zehavi T.,
RA Raas-Rothschild A., Mao C., Mueller T.;
RT "Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with
RT congenital nephrotic syndrome and congenital adrenal calcifications.";
RL Hum. Mutat. 38:365-372(2017).
RN [16]
RP INVOLVEMENT IN NPHS14, VARIANTS NPHS14 GLN-222; TRP-222; ILE-346 AND
RP CYS-416, CHARACTERIZATION OF VARIANTS NPHS14 GLN-222 AND ILE-346, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF GLU-132.
RX PubMed=28165339; DOI=10.1172/jci89626;
RA Lovric S., Goncalves S., Gee H.Y., Oskouian B., Srinivas H., Choi W.I.,
RA Shril S., Ashraf S., Tan W., Rao J., Airik M., Schapiro D., Braun D.A.,
RA Sadowski C.E., Widmeier E., Jobst-Schwan T., Schmidt J.M., Girik V.,
RA Capitani G., Suh J.H., Lachaussee N., Arrondel C., Patat J., Gribouval O.,
RA Furlano M., Boyer O., Schmitt A., Vuiblet V., Hashmi S., Wilcken R.,
RA Bernier F.P., Innes A.M., Parboosingh J.S., Lamont R.E., Midgley J.P.,
RA Wright N., Majewski J., Zenker M., Schaefer F., Kuss N., Greil J.,
RA Giese T., Schwarz K., Catheline V., Schanze D., Franke I., Sznajer Y.,
RA Truant A.S., Adams B., Desir J., Biemann R., Pei Y., Ars E., Lloberas N.,
RA Madrid A., Dharnidharka V.R., Connolly A.M., Willing M.C., Cooper M.A.,
RA Lifton R.P., Simons M., Riezman H., Antignac C., Saba J.D., Hildebrandt F.;
RT "Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis
RT and adrenal insufficiency.";
RL J. Clin. Invest. 127:912-928(2017).
RN [17]
RP INVOLVEMENT IN NPHS14, VARIANTS NPHS14 GLN-222 AND PHE-545 DEL,
RP CHARACTERIZATION OF VARIANTS NPHS14 GLN-222 AND PHE-545 DEL, AND TISSUE
RP SPECIFICITY.
RX PubMed=28165343; DOI=10.1172/jci90171;
RA Prasad R., Hadjidemetriou I., Maharaj A., Meimaridou E., Buonocore F.,
RA Saleem M., Hurcombe J., Bierzynska A., Barbagelata E., Bergada I.,
RA Cassinelli H., Das U., Krone R., Hacihamdioglu B., Sari E., Yesilkaya E.,
RA Storr H.L., Clemente M., Fernandez-Cancio M., Camats N., Ram N.,
RA Achermann J.C., Van Veldhoven P.P., Guasti L., Braslavsky D., Guran T.,
RA Metherell L.A.;
RT "Sphingosine-1-phosphate lyase mutations cause primary adrenal
RT insufficiency and steroid-resistant nephrotic syndrome.";
RL J. Clin. Invest. 127:942-953(2017).
RN [18]
RP INVOLVEMENT IN NPHS14, AND VARIANT NPHS14 TRP-340.
RX PubMed=30090628; DOI=10.1093/ckj/sfx130;
RA Linhares N.D., Arantes R.R., Araujo S.A., Pena S.D.J.;
RT "Nephrotic syndrome and adrenal insufficiency caused by a variant in
RT SGPL1.";
RL Clin. Kidney J. 11:462-467(2018).
RN [19]
RP VARIANTS THR-184 AND 361-SER--HIS-568 DEL.
RX PubMed=28077491; DOI=10.1212/wnl.0000000000003595;
RA Atkinson D., Nikodinovic Glumac J., Asselbergh B., Ermanoska B.,
RA Blocquel D., Steiner R., Estrada-Cuzcano A., Peeters K., Ooms T.,
RA De Vriendt E., Yang X.L., Hornemann T., Milic Rasic V., Jordanova A.;
RT "Sphingosine 1-phosphate lyase deficiency causes Charcot-Marie-Tooth
RT neuropathy.";
RL Neurology 88:533-542(2017).
RN [20]
RP VARIANTS LEU-21 AND GLN-222.
RX PubMed=30517686; DOI=10.1210/jc.2018-02238;
RA Settas N., Persky R., Faucz F.R., Sheanon N., Voutetakis A., Lodish M.,
RA Metherell L.A., Stratakis C.A.;
RT "SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency.";
RL J. Clin. Endocrinol. Metab. 104:1484-1490(2019).
RN [21]
RP REVIEW OF FUNCTION.
RX PubMed=30635364; DOI=10.1194/jlr.s091181;
RA Saba J.D.;
RT "Fifty years of lyase and a moment of truth: Sphingosine phosphate lyase
RT from discovery to disease.";
RL J. Lipid Res. 60:456-463(2019).
CC -!- FUNCTION: Cleaves phosphorylated sphingoid bases (PSBs), such as
CC sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine.
CC Elevates stress-induced ceramide production and apoptosis
CC (PubMed:11018465, PubMed:14570870, PubMed:24809814, PubMed:28165339).
CC Required for global lipid homeostasis in liver and cholesterol
CC homeostasis in fibroblasts. Involved in the regulation of pro-
CC inflammatory response and neutrophil trafficking. Modulates neuronal
CC autophagy via phosphoethanolamine production which regulates
CC accumulation of aggregate-prone proteins such as APP (By similarity).
CC Seems to play a role in establishing neuronal contact sites and axonal
CC maintenance (By similarity). {ECO:0000250|UniProtKB:Q8R0X7,
CC ECO:0000250|UniProtKB:Q9V7Y2, ECO:0000269|PubMed:11018465,
CC ECO:0000269|PubMed:14570870, ECO:0000269|PubMed:24809814,
CC ECO:0000269|PubMed:28165339}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine 1-phosphate = hexadecanal + phosphoethanolamine;
CC Xref=Rhea:RHEA:18593, ChEBI:CHEBI:17600, ChEBI:CHEBI:57939,
CC ChEBI:CHEBI:58190; EC=4.1.2.27;
CC Evidence={ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:22784711,
CC ECO:0000269|PubMed:24809814, ECO:0000269|PubMed:28165339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18594;
CC Evidence={ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:22784711};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphing-4-enine 1-phosphate = (2E)-hexadecenal +
CC phosphoethanolamine; Xref=Rhea:RHEA:33507, ChEBI:CHEBI:17585,
CC ChEBI:CHEBI:58190, ChEBI:CHEBI:60119; EC=4.1.2.27;
CC Evidence={ECO:0000269|PubMed:22784711};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33508;
CC Evidence={ECO:0000269|PubMed:22784711};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:24809814};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.2 uM for sphingosine 1-phosphate {ECO:0000269|PubMed:24809814};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:24809814,
CC ECO:0000269|PubMed:28165339}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24809814}.
CC -!- INTERACTION:
CC O95470; Q92482: AQP3; NbExp=3; IntAct=EBI-1046170, EBI-2808854;
CC O95470; O43315: AQP9; NbExp=3; IntAct=EBI-1046170, EBI-17444777;
CC O95470; Q92843: BCL2L2; NbExp=3; IntAct=EBI-1046170, EBI-707714;
CC O95470; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-1046170, EBI-12244618;
CC O95470; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-1046170, EBI-10271156;
CC O95470; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-1046170, EBI-12256978;
CC O95470; P52803: EFNA5; NbExp=3; IntAct=EBI-1046170, EBI-1753674;
CC O95470; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-1046170, EBI-711490;
CC O95470; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-1046170, EBI-11337888;
CC O95470; Q8N128-2: FAM177A1; NbExp=3; IntAct=EBI-1046170, EBI-12201693;
CC O95470; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-1046170, EBI-12175685;
CC O95470; P30519: HMOX2; NbExp=3; IntAct=EBI-1046170, EBI-712096;
CC O95470; Q01628: IFITM3; NbExp=3; IntAct=EBI-1046170, EBI-7932862;
CC O95470; Q9NX47: MARCHF5; NbExp=3; IntAct=EBI-1046170, EBI-2341610;
CC O95470; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-1046170, EBI-2858252;
CC O95470; P30301: MIP; NbExp=3; IntAct=EBI-1046170, EBI-8449636;
CC O95470; Q8IY49-2: MMD2; NbExp=3; IntAct=EBI-1046170, EBI-13349813;
CC O95470; Q9NXK6: PAQR5; NbExp=3; IntAct=EBI-1046170, EBI-10316423;
CC O95470; Q04941: PLP2; NbExp=3; IntAct=EBI-1046170, EBI-608347;
CC O95470; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-1046170, EBI-10485931;
CC O95470; Q5GAN6: RNASE10; NbExp=3; IntAct=EBI-1046170, EBI-12423312;
CC O95470; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-1046170, EBI-10244780;
CC O95470; Q8TAC9: SCAMP5; NbExp=3; IntAct=EBI-1046170, EBI-2695784;
CC O95470; Q99726: SLC30A3; NbExp=3; IntAct=EBI-1046170, EBI-10294651;
CC O95470; P02808: STATH; NbExp=3; IntAct=EBI-1046170, EBI-738687;
CC O95470; Q86WV6: STING1; NbExp=2; IntAct=EBI-1046170, EBI-2800345;
CC O95470; Q12846: STX4; NbExp=3; IntAct=EBI-1046170, EBI-744942;
CC O95470; Q9UNK0: STX8; NbExp=3; IntAct=EBI-1046170, EBI-727240;
CC O95470; Q96HP8: TMEM176A; NbExp=3; IntAct=EBI-1046170, EBI-2800645;
CC O95470; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-1046170, EBI-10315004;
CC O95470; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-1046170, EBI-12111910;
CC O95470; O14817: TSPAN4; NbExp=3; IntAct=EBI-1046170, EBI-8652667;
CC O95470; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-1046170, EBI-11988865;
CC O95470; Q53HI1: UNC50; NbExp=3; IntAct=EBI-1046170, EBI-7601760;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14570870}; Single-pass type III membrane protein
CC {ECO:0000255}; Cytoplasmic side {ECO:0000250|UniProtKB:Q8R0X7}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:11018465,
CC PubMed:28165343). Expressed in fetal and adult adrenal gland (at
CC protein level) (PubMed:28165343). {ECO:0000269|PubMed:11018465,
CC ECO:0000269|PubMed:28165343}.
CC -!- DISEASE: Nephrotic syndrome 14 (NPHS14) [MIM:617575]: A form of
CC nephrotic syndrome, a renal disease clinically characterized by severe
CC proteinuria, resulting in complications such as hypoalbuminemia,
CC hyperlipidemia and edema. Kidney biopsies show non-specific histologic
CC changes such as focal segmental glomerulosclerosis and diffuse
CC mesangial proliferation. NPHS14 is an autosomal recessive syndromic,
CC steroid-resistant form that progresses to end-stage renal failure. Some
CC NPHS14 patients manifest ichthyosis, adrenal insufficiency,
CC immunodeficiency, and neurological defects.
CC {ECO:0000269|PubMed:28165339, ECO:0000269|PubMed:28165343,
CC ECO:0000269|PubMed:28181337, ECO:0000269|PubMed:30090628}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family. Sphingosine-
CC 1-phosphate lyase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86566.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ011304; CAA09590.2; -; mRNA.
DR EMBL; AF144638; AAD44755.1; -; mRNA.
DR EMBL; AB033078; BAA86566.1; ALT_INIT; mRNA.
DR EMBL; AK314615; BAG37181.1; -; mRNA.
DR EMBL; CH471083; EAW54414.1; -; Genomic_DNA.
DR EMBL; BC052991; AAH52991.1; -; mRNA.
DR CCDS; CCDS31216.1; -.
DR RefSeq; NP_003892.2; NM_003901.3.
DR RefSeq; XP_005270320.1; XM_005270263.1.
DR RefSeq; XP_011538618.1; XM_011540316.2.
DR RefSeq; XP_011538619.1; XM_011540317.1.
DR PDB; 4Q6R; X-ray; 2.40 A; A/B=62-568.
DR PDBsum; 4Q6R; -.
DR AlphaFoldDB; O95470; -.
DR SMR; O95470; -.
DR BioGRID; 114398; 202.
DR IntAct; O95470; 81.
DR MINT; O95470; -.
DR STRING; 9606.ENSP00000362298; -.
DR BindingDB; O95470; -.
DR ChEMBL; CHEMBL3286061; -.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugCentral; O95470; -.
DR GuidetoPHARMACOLOGY; 2522; -.
DR SwissLipids; SLP:000000107; -.
DR iPTMnet; O95470; -.
DR MetOSite; O95470; -.
DR PhosphoSitePlus; O95470; -.
DR SwissPalm; O95470; -.
DR BioMuta; SGPL1; -.
DR EPD; O95470; -.
DR jPOST; O95470; -.
DR MassIVE; O95470; -.
DR MaxQB; O95470; -.
DR PaxDb; O95470; -.
DR PeptideAtlas; O95470; -.
DR PRIDE; O95470; -.
DR ProteomicsDB; 50902; -.
DR Antibodypedia; 14941; 180 antibodies from 23 providers.
DR DNASU; 8879; -.
DR Ensembl; ENST00000373202.8; ENSP00000362298.3; ENSG00000166224.17.
DR GeneID; 8879; -.
DR KEGG; hsa:8879; -.
DR MANE-Select; ENST00000373202.8; ENSP00000362298.3; NM_003901.4; NP_003892.2.
DR UCSC; uc001jrm.4; human.
DR CTD; 8879; -.
DR DisGeNET; 8879; -.
DR GeneCards; SGPL1; -.
DR GeneReviews; SGPL1; -.
DR HGNC; HGNC:10817; SGPL1.
DR HPA; ENSG00000166224; Low tissue specificity.
DR MalaCards; SGPL1; -.
DR MIM; 603729; gene.
DR MIM; 617575; phenotype.
DR neXtProt; NX_O95470; -.
DR OpenTargets; ENSG00000166224; -.
DR Orphanet; 506334; Familial steroid-resistant nephrotic syndrome with adrenal insufficiency.
DR PharmGKB; PA35725; -.
DR VEuPathDB; HostDB:ENSG00000166224; -.
DR eggNOG; KOG1383; Eukaryota.
DR GeneTree; ENSGT00390000000046; -.
DR HOGENOM; CLU_028929_1_1_1; -.
DR InParanoid; O95470; -.
DR OMA; FKDHQFT; -.
DR OrthoDB; 517323at2759; -.
DR PhylomeDB; O95470; -.
DR TreeFam; TF300777; -.
DR BRENDA; 4.1.2.27; 2681.
DR PathwayCommons; O95470; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; O95470; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 8879; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; SGPL1; human.
DR GeneWiki; SGPL1; -.
DR GenomeRNAi; 8879; -.
DR Pharos; O95470; Tchem.
DR PRO; PR:O95470; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O95470; protein.
DR Bgee; ENSG00000166224; Expressed in esophagus squamous epithelium and 187 other tissues.
DR ExpressionAtlas; O95470; baseline and differential.
DR Genevisible; O95470; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; NAS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008117; F:sphinganine-1-phosphate aldolase activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; IEA:Ensembl.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IEA:Ensembl.
DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl.
DR GO; GO:0001553; P:luteinization; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0048705; P:skeletal system morphogenesis; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0030149; P:sphingolipid catabolic process; IDA:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR002129; PyrdxlP-dep_de-COase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00282; Pyridoxal_deC; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Disease variant;
KW Endoplasmic reticulum; Lipid metabolism; Lyase; Membrane; Nitration;
KW Phosphoprotein; Pyridoxal phosphate; Reference proteome; Signal-anchor;
KW Sphingolipid metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..568
FT /note="Sphingosine-1-phosphate lyase 1"
FT /id="PRO_0000147012"
FT TOPO_DOM 1..40
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..568
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 353
FT /note="N6-(pyridoxal phosphate)lysine; alternate"
FT MOD_RES 353
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 356
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16777052"
FT MOD_RES 366
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16777052"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VARIANT 21
FT /note="V -> L (in dbSNP:rs12770335)"
FT /evidence="ECO:0000269|PubMed:30517686"
FT /id="VAR_048875"
FT VARIANT 184
FT /note="I -> T (probable disease-associated variant found in
FT patients with atypical form of axonal peripheral
FT neuropathy, characterized by acute or subacute onset and
FT episodes of recurrent mononeuropathy; dbSNP:rs201533115)"
FT /evidence="ECO:0000269|PubMed:28077491"
FT /id="VAR_081454"
FT VARIANT 222
FT /note="R -> Q (in NPHS14; probable disease-associated
FT variant also found in a patient with isolated primary
FT adrenal insufficiency; decreased protein abundance;
FT increased aggregation; decreased sphinganine-1-phosphate
FT aldolase activity; dbSNP:rs769259446)"
FT /evidence="ECO:0000269|PubMed:28165339,
FT ECO:0000269|PubMed:28165343, ECO:0000269|PubMed:30517686"
FT /id="VAR_079213"
FT VARIANT 222
FT /note="R -> W (in NPHS14; dbSNP:rs1131692255)"
FT /evidence="ECO:0000269|PubMed:28165339"
FT /id="VAR_079214"
FT VARIANT 340
FT /note="R -> W (in NPHS14; unknown pathological
FT significance; dbSNP:rs1437439236)"
FT /evidence="ECO:0000269|PubMed:30090628"
FT /id="VAR_081455"
FT VARIANT 346
FT /note="S -> I (in NPHS1; decreased protein abundance in
FT cells of patients homozygous for the mutation; increased
FT aggregation; decreased sphinganine-1-phosphate aldolase
FT activity; dbSNP:rs1131692256)"
FT /evidence="ECO:0000269|PubMed:28165339"
FT /id="VAR_079215"
FT VARIANT 361..568
FT /note="Missing (probable disease-associated variant found
FT in patients with atypical form of axonal peripheral
FT neuropathy, characterized by acute or subacute onset and
FT episodes of recurrent mononeuropathy)"
FT /evidence="ECO:0000269|PubMed:28077491"
FT /id="VAR_081456"
FT VARIANT 416
FT /note="Y -> C (in NPHS14; unknown pathological
FT significance; dbSNP:rs779485098)"
FT /evidence="ECO:0000269|PubMed:28165339"
FT /id="VAR_079216"
FT VARIANT 505..568
FT /note="Missing (in NPHS14)"
FT /evidence="ECO:0000269|PubMed:28181337"
FT /id="VAR_079217"
FT VARIANT 545
FT /note="Missing (in NPHS14; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:28165343"
FT /id="VAR_079218"
FT MUTAGEN 132
FT /note="E->G: No effect on the sphinganine-1-phosphate
FT aldolase activity; no effect on protein abundance."
FT /evidence="ECO:0000269|PubMed:28165339"
FT MUTAGEN 218
FT /note="C->G: Loss of sphinganine-1-phosphate aldolase
FT activity."
FT /evidence="ECO:0000269|PubMed:11018465"
FT MUTAGEN 317
FT /note="C->S: Almost no sphinganine-1-phosphate aldolase
FT activity."
FT /evidence="ECO:0000269|PubMed:11018465"
FT MUTAGEN 353
FT /note="K->L: Loss of sphinganine-1-phosphate aldolase
FT activity."
FT /evidence="ECO:0000269|PubMed:14570870"
FT CONFLICT 404
FT /note="C -> A (in Ref. 1; CAA09590)"
FT /evidence="ECO:0000305"
FT HELIX 123..134
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 154..165
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 179..195
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 203..209
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 210..227
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 269..273
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 298..308
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 324..330
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 344..349
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 362..368
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 387..392
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 398..434
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 448..454
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 461..469
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:4Q6R"
FT TURN 478..481
FT /evidence="ECO:0007829|PDB:4Q6R"
FT STRAND 482..486
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 489..494
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 497..513
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 521..531
FT /evidence="ECO:0007829|PDB:4Q6R"
FT HELIX 535..549
FT /evidence="ECO:0007829|PDB:4Q6R"
SQ SEQUENCE 568 AA; 63524 MW; 3B16FDEFC4B2FDB6 CRC64;
MPSTDLLMLK AFEPYLEILE VYSTKAKNYV NGHCTKYEPW QLIAWSVVWT LLIVWGYEFV
FQPESLWSRF KKKCFKLTRK MPIIGRKIQD KLNKTKDDIS KNMSFLKVDK EYVKALPSQG
LSSSAVLEKL KEYSSMDAFW QEGRASGTVY SGEEKLTELL VKAYGDFAWS NPLHPDIFPG
LRKIEAEIVR IACSLFNGGP DSCGCVTSGG TESILMACKA YRDLAFEKGI KTPEIVAPQS
AHAAFNKAAS YFGMKIVRVP LTKMMEVDVR AMRRAISRNT AMLVCSTPQF PHGVIDPVPE
VAKLAVKYKI PLHVDACLGG FLIVFMEKAG YPLEHPFDFR VKGVTSISAD THKYGYAPKG
SSLVLYSDKK YRNYQFFVDT DWQGGIYASP TIAGSRPGGI SAACWAALMH FGENGYVEAT
KQIIKTARFL KSELENIKGI FVFGNPQLSV IALGSRDFDI YRLSNLMTAK GWNLNQLQFP
PSIHFCITLL HARKRVAIQF LKDIRESVTQ IMKNPKAKTT GMGAIYGMAQ TTVDRNMVAE
LSSVFLDSLY STDTVTQGSQ MNGSPKPH
