SPHKA_DICDI
ID SPHKA_DICDI Reviewed; 624 AA.
AC Q86KF9; Q559I0;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Sphingosine kinase A;
DE Short=SK A;
DE Short=SPK A;
DE EC=2.7.1.91 {ECO:0000250|UniProtKB:Q9NRA0};
GN Name=sgkA; Synonyms=SK, SPHK; ORFNames=DDB_G0272522;
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], DISRUPTION PHENOTYPE, OVEREXPRESSION, POSSIBLE
RP SUBCELLULAR LOCATION, AND INHIBITION.
RC STRAIN=AX4;
RX PubMed=15643073; DOI=10.1128/ec.4.1.178-189.2005;
RA Min J., Traynor D., Stegner A.L., Zhang L., Hanigan M.H., Alexander H.,
RA Alexander S.;
RT "Sphingosine kinase regulates the sensitivity of Dictyostelium discoideum
RT cells to the anticancer drug cisplatin.";
RL Eukaryot. Cell 4:178-189(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [3]
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).
CC -!- FUNCTION: Catalyzes the phosphorylation of sphingosine to form
CC sphingosine-1-phosphate (S1P), which probably acts intracellularly as a
CC second messenger perhaps by promoting cell proliferation.
CC Overexpression of sgkA leads to increased growth rates on solid media
CC and an increased resistance to the antitumor agents cisplatin and
CC carboplatin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:51496, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:76941, ChEBI:CHEBI:84410, ChEBI:CHEBI:456216;
CC EC=2.7.1.91; Evidence={ECO:0000250|UniProtKB:Q9NRA0};
CC -!- ACTIVITY REGULATION: Inhibited by N,N,-dimethylsphingosine; this
CC inhibitor increases sensitivity to cisplatin.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}.
CC Note=Determined in cells overexpressing sgkA. Also appears enriched in
CC some pseudopodia.
CC -!- DISRUPTION PHENOTYPE: Cells grow more slowly on solid media and are
CC more sensitive than wild-type to the antitumor agents cisplatin and
CC carboplatin; both effects are exacerbated in sgkA and sgkB double
CC knockout. Exogenous S1P reverses the sensitivity to cisplatin.
CC {ECO:0000269|PubMed:15643073}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY283053; AAP37028.1; -; mRNA.
DR EMBL; AAFI02000008; EAL71185.1; -; Genomic_DNA.
DR RefSeq; XP_645126.1; XM_640034.1.
DR AlphaFoldDB; Q86KF9; -.
DR SMR; Q86KF9; -.
DR STRING; 44689.DDB0185181; -.
DR PaxDb; Q86KF9; -.
DR EnsemblProtists; EAL71185; EAL71185; DDB_G0272522.
DR GeneID; 8618520; -.
DR KEGG; ddi:DDB_G0272522; -.
DR dictyBase; DDB_G0272522; sgkA.
DR eggNOG; KOG1116; Eukaryota.
DR HOGENOM; CLU_438347_0_0_1; -.
DR InParanoid; Q86KF9; -.
DR OMA; AHHCNEP; -.
DR PhylomeDB; Q86KF9; -.
DR Reactome; R-DDI-1483206; Glycerophospholipid biosynthesis.
DR Reactome; R-DDI-1660661; Sphingolipid de novo biosynthesis.
DR PRO; PR:Q86KF9; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:dictyBase.
DR GO; GO:0031143; C:pseudopodium; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IDA:dictyBase.
DR GO; GO:0017050; F:D-erythro-sphingosine kinase activity; IDA:dictyBase.
DR GO; GO:0001727; F:lipid kinase activity; IBA:GO_Central.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0008481; F:sphinganine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006648; P:dihydrosphingosine-1-P pathway; IDA:dictyBase.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:1903666; P:positive regulation of asexual reproduction; IMP:dictyBase.
DR GO; GO:1904643; P:response to curcumin; IMP:dictyBase.
DR GO; GO:0006665; P:sphingolipid metabolic process; IBA:GO_Central.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR InterPro; IPR045540; YegS/DAGK_C.
DR Pfam; PF00781; DAGK_cat; 1.
DR Pfam; PF19279; YegS_C; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Lipid metabolism; Nucleotide-binding;
KW Nucleus; Reference proteome; Sphingolipid metabolism; Transferase.
FT CHAIN 1..624
FT /note="Sphingosine kinase A"
FT /id="PRO_0000328250"
FT DOMAIN 178..314
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 246
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 188..190
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 244..247
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 276..278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 332
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 599..601
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
SQ SEQUENCE 624 AA; 70024 MW; 485BC2B1B8028317 CRC64;
MSINSDYNKE NNNISPLNTS SERRSSLRNS LNNSSNNNNN NVINTPTANS INSSGNFSPK
EFVSNIDGEE IIYQNQSVEY KQRLCTIQIK QSTLIIKFNE KGGFTKYLVS DTIVGSEITN
ESTNEYTIYS CVMNTLDVTK ETRRRKQFSL RFRDRFELNQ FNDKFVEAFL DTLPMGNPRE
RRIRVILNPK SGKKMSDSIF KDINELFKDS KIFVKKTVTK GPDHAKKIGY KFNLKKYDTI
VFISGDGLFH EFINGLLSRT DFEQARKIPL ALIPGGTGNG IACSIGLQDP MSCALAVIRG
FTKPLDVSVI QQGDKKWCSI LSLTWGIVSD VDIESEKYRA LGDVRLILGA ALRILNLRIY
RGKIWYLPAL ELNKTEIAKI PKCSYSCEIC ESDNPISTIE NVISQQQQNN TTTNQLRRSS
LNNSSNGFSP KLNTSGSISN GNDDELRSMF SKEENIKIEN EIHDHQNDDV LPLLKSSSDQ
HFIVPPTKLP NQQFLKETKE ELFAKGWKVL EGEFIGIVAS TVSHLASDFI ASPTAHLSDG
LIDLVVINNN KKFSKAGLLS VLTESSTGAH VKSDLIDQYK VQAMILEPSN DREGIIAVDG
ELISYGRTSM ECMRACINLI CRTY
