SPHKB_DICDI
ID SPHKB_DICDI Reviewed; 760 AA.
AC Q6B516; Q54PJ2;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Sphingosine kinase B;
DE Short=SK B;
DE Short=SPK B;
DE EC=2.7.1.91 {ECO:0000250|UniProtKB:Q9NRA0};
GN Name=sgkB; Synonyms=SK, SPHK; ORFNames=DDB_G0284545;
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], AND DISRUPTION PHENOTYPE.
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=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 -!- 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.
CC {ECO:0000305}.
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}.
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DR EMBL; AY679519; AAT80892.1; -; mRNA.
DR EMBL; AAFI02000066; EAL65199.1; -; Genomic_DNA.
DR RefSeq; XP_638540.1; XM_633448.1.
DR AlphaFoldDB; Q6B516; -.
DR SMR; Q6B516; -.
DR STRING; 44689.DDB0220131; -.
DR PaxDb; Q6B516; -.
DR EnsemblProtists; EAL65199; EAL65199; DDB_G0284545.
DR GeneID; 8624633; -.
DR KEGG; ddi:DDB_G0284545; -.
DR dictyBase; DDB_G0284545; sgkB.
DR eggNOG; KOG1116; Eukaryota.
DR HOGENOM; CLU_438347_0_0_1; -.
DR InParanoid; Q6B516; -.
DR OMA; AAGCKLD; -.
DR PhylomeDB; Q6B516; -.
DR Reactome; R-DDI-1483206; Glycerophospholipid biosynthesis.
DR Reactome; R-DDI-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-DDI-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-DDI-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-DDI-9009391; Extra-nuclear estrogen signaling.
DR PRO; PR:Q6B516; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
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: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; Kinase; Lipid metabolism; Nucleotide-binding;
KW Reference proteome; Sphingolipid metabolism; Transferase.
FT CHAIN 1..760
FT /note="Sphingosine kinase B"
FT /id="PRO_0000328251"
FT DOMAIN 247..383
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REGION 1..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 535..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..605
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 315
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 257..259
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 288
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 313..316
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 345..347
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 461
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 468
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 474
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 734..736
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
SQ SEQUENCE 760 AA; 83966 MW; D505C2167ACB266C CRC64;
MENNNNEPAE TVQEKGPKLK NDIDLNDQFK DEKEKKEEIS SSSIENKNNN NNNTSTNNVI
PNESNNNISN NNVISNENNN TNNNTDNNTD NNNNNNNNNN NNNEPVTSFT VNNKSLIEKE
PTLFEFNQEQ QIKYKNKSIN SLIIKRSGIV IKISQKKSTI IYQDSIIACS ELPDNFDTAT
TTTTTTTTLP IKVTLFTCVL KKKQLTIDKE QRKRKSYTFQ FKSNQDSLNF YSNIQSTFLN
SLPRGNPKNR KIRILINPKS GKKESHNIFK EVEQLFKDSG IKMKLTVTME PEHAKKIGFK
SNIYKYDTVV FISGDGLLHE FINGLLSRED YEDAKKIPLA LIPAGTGNGL ANSIGLQDPM
SAALAILRGF TKPLDVCIVQ QPTVTTIPVV DNNTVTTTTT TTSPTSASPT ITSANNNNNN
NNNNNNNNNN NNNNNNNNNN SNITKWCSIL SLTWGLVSDV DIESEKYRSL GDLRLIIGAA
VRILNLRIYR GKVYFLPAIP LDKSQMQSIP KCSFDCNICD SSNSVKVIED LVCNDNDNNN
KNKNEEQNEI NSTTSNNNNN NNTTTTSTSS STSTSTSTSS LTATTTTAKS TNSLSSSPRS
DINMSSNSIS KSLDIGTIPS CKVTHNSNLL NESSDSLLSK GWKCIEGEFI GVVASTVSHL
ASDFISSPNA HLSDGLIDLI FINNRSKLSK ASLLSILTDS ATGDHLKSDL IEHHKVKALI
LEPSIQKHGI VAIDGERIPY AKTSMENIRG CLNLICRSYH
