SGPL_DICDI
ID SGPL_DICDI Reviewed; 528 AA.
AC Q54RV9; Q7Z271; Q9NC67;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 25-MAY-2022, entry version 103.
DE RecName: Full=Sphingosine-1-phosphate lyase;
DE Short=S1P lyase;
DE Short=S1PL;
DE Short=SP-lyase;
DE Short=SPL;
DE EC=4.1.2.27;
DE AltName: Full=Sphingosine-1-phosphate aldolase;
GN Name=sglA; ORFNames=DDB_G0282819;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX4;
RX PubMed=11566853; DOI=10.1242/dev.128.18.3473;
RA Li G., Foote C., Alexander S., Alexander H.;
RT "Sphingosine-1-phosphate lyase has a central role in the development of
RT Dictyostelium discoideum.";
RL Development 128:3473-3483(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 232-270, GENE EXPRESSION, RESISTANCE
RP TO CISPLATIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX4;
RX PubMed=10974109; DOI=10.1099/00221287-146-9-2219;
RA Li G., Alexander H., Schneider N., Alexander S.;
RT "Molecular basis for resistance to the anticancer drug cisplatin in
RT Dictyostelium.";
RL Microbiology 146:2219-2227(2000).
RN [4]
RP FUNCTION.
RC STRAIN=AX4;
RX PubMed=15476260; DOI=10.1002/cm.20035;
RA Kumar A., Wessels D., Daniels K.J., Alexander H., Alexander S., Soll D.R.;
RT "Sphingosine-1-phosphate plays a role in the suppression of lateral
RT pseudopod formation during Dictyostelium discoideum cell migration and
RT chemotaxis.";
RL Cell Motil. Cytoskeleton 59:227-241(2004).
RN [5]
RP OVEREXPRESSING STRAINS ARE MORE SENSITIVE TO CISPLATIN, AND A MODEL OF
RP CISPLATIN-RESISTANCE.
RC STRAIN=AX3;
RX PubMed=15190000; DOI=10.1128/ec.3.3.795-805.2004;
RA Min J., Stegner A.L., Alexander H., Alexander S.;
RT "Overexpression of sphingosine-1-phosphate lyase or inhibition of
RT sphingosine kinase in Dictyostelium discoideum results in a selective
RT increase in sensitivity to platinum-based chemotherapy drugs.";
RL Eukaryot. Cell 3:795-805(2004).
CC -!- FUNCTION: Cleaves phosphorylated sphingoid bases (PSBs), such as
CC sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine
CC (By similarity). Sphingosine-1-phosphate (S1P) probably acts
CC intracellularly as a second messenger perhaps by promoting cell
CC proliferation; the absence of S1P lyase increases its concentration.
CC This leads to increased lateral pseudopod formation as well as defects
CC in the efficiency of chemotaxis (PubMed:15476260). Overexpression of
CC S1P lyase causes decreased growth rates, entry into stationary phase at
CC lower cell density and increased sensitivity to the antitumor agents
CC cisplatin and carboplatin; these effects are more pronounced in cells
CC that express more enzyme (PubMed:15190000). {ECO:0000250,
CC ECO:0000269|PubMed:15190000, ECO:0000269|PubMed:15476260}.
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 -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Constitutively expressed during growth and
CC development; not up-regulated by exposure to cisplatin.
CC {ECO:0000269|PubMed:11566853}.
CC -!- DISRUPTION PHENOTYPE: Cells produce short fruiting bodies with a thick
CC stalk and drastically reduced numbers of spores. Mutant cells grow
CC exponentially at the same rate as wild-type and are 25-fold more
CC resistant to the antitumor agent cisplatin than are wild-type
CC (PubMed:11566853). Mutant cells survive longer in stationary phase than
CC wild-type cells, but are effected at multiple stages of development.
CC Addition of 50 uM extracellular sphingosine-1-phosphate to wild-type
CC cells mimics the developmental effect of the knockout
CC (PubMed:11566853), and leads to increased cisplatin resistance
CC (PubMed:15190000). {ECO:0000269|PubMed:10974109,
CC ECO:0000269|PubMed:11566853, ECO:0000269|PubMed:15190000}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family. Sphingosine-
CC 1-phosphate lyase subfamily. {ECO:0000305}.
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DR EMBL; AY283052; AAP37027.1; -; mRNA.
DR EMBL; AAFI02000047; EAL65989.1; -; Genomic_DNA.
DR EMBL; AF233610; AAF97870.1; -; Genomic_DNA.
DR RefSeq; XP_639378.1; XM_634286.1.
DR AlphaFoldDB; Q54RV9; -.
DR SMR; Q54RV9; -.
DR STRING; 44689.DDB0214888; -.
DR PaxDb; Q54RV9; -.
DR EnsemblProtists; EAL65989; EAL65989; DDB_G0282819.
DR GeneID; 8623817; -.
DR KEGG; ddi:DDB_G0282819; -.
DR dictyBase; DDB_G0282819; sglA.
DR eggNOG; KOG1383; Eukaryota.
DR HOGENOM; CLU_028929_1_0_1; -.
DR InParanoid; Q54RV9; -.
DR OMA; FKDHQFT; -.
DR PhylomeDB; Q54RV9; -.
DR BRENDA; 4.1.2.27; 1939.
DR Reactome; R-DDI-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q54RV9; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008117; F:sphinganine-1-phosphate aldolase activity; IBA:GO_Central.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:dictyBase.
DR GO; GO:0001667; P:ameboidal-type cell migration; IMP:dictyBase.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
DR GO; GO:0008219; P:cell death; IMP:dictyBase.
DR GO; GO:0048870; P:cell motility; IMP:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IMP:dictyBase.
DR GO; GO:0120320; P:lateral pseudopodium retraction; IMP:dictyBase.
DR GO; GO:0031158; P:negative regulation of aggregate size involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0046956; P:positive phototaxis; IMP:dictyBase.
DR GO; GO:0097328; P:response to carboplatin; IMP:dictyBase.
DR GO; GO:0072718; P:response to cisplatin; IMP:dictyBase.
DR GO; GO:0031153; P:slug development involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
DR GO; GO:0030149; P:sphingolipid catabolic process; IBA:GO_Central.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:dictyBase.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid metabolism; Lyase; Membrane;
KW Pyridoxal phosphate; Reference proteome; Signal-anchor;
KW Sphingolipid metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..528
FT /note="Sphingosine-1-phosphate lyase"
FT /id="PRO_0000328248"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 324
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
FT CONFLICT 90
FT /note="K -> R (in Ref. 1; AAP37027)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="D -> G (in Ref. 1; AAP37027)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 528 AA; 58239 MW; 7C9411C9C73BBDA8 CRC64;
MDKANDYLKD YQPAKLVLAT AGITAASILA YQAITDRDFK DKLNKKIFRS IKSMPGVSDI
VKKERAKAKV ELKKMFKTDV RNAHYTLPLK GIKHEDLIEE MKALAKVDES HWVDSKVSGC
VYLGEKEHTK LLNEAYSLFS LSNPLHPSVF PSIRKFETES ISMVSNMLNA HSKVVGSLTS
GGTESIFMAV KAYRDFYKDR TDRPEIVVPV TIHAAFDKAC EYLKIRIVHI DVDPVSYKVD
MAAMKKAINK DTILVAGSAV NFPHGIIDPI DEIAKLAQQY DIGCHVDACL GGFILPFAEK
LDYDIPVFDF RIPGVTSMSV DTHKFGYAAK GTSVVLFGNK KLRRAMYFVA PNWPGGIYAS
PTLPGSRPGG LVAACWASLV SMGNDGFLEK AKGVMETTKK IIKGLQSING VKIIGDPKAM
VVAFTCDNIF YVNDYMSKKG WHLNALQRPN SLHVCVTAKM IGMESLFIED LKDSIKLVKD
NSGSLPKDGT APIYGSAHSV PDREMVGTIL SDFIDELITP DYKPSQST
