SPHK1_CAEEL
ID SPHK1_CAEEL Reviewed; 473 AA.
AC Q18425; D2Y8W1; H9G2Q9; Q7JM91;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Sphingosine kinase 1;
DE EC=2.7.1.91 {ECO:0000305};
GN Name=sphk-1; Synonyms=tag-274; ORFNames=C34C6.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 151-SER--LEU-155; 184-GLY--ASN-187 AND 271-PHE-ILE-272.
RX PubMed=22588719; DOI=10.1101/gad.188003.112;
RA Chan J.P., Hu Z., Sieburth D.;
RT "Recruitment of sphingosine kinase to presynaptic terminals by a conserved
RT muscarinic signaling pathway promotes neurotransmitter release.";
RL Genes Dev. 26:1070-1085(2012).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23223309; DOI=10.1523/jneurosci.2808-12.2012;
RA Chan J.P., Sieburth D.;
RT "Localized sphingolipid signaling at presynaptic terminals is regulated by
RT calcium influx and promotes recruitment of priming factors.";
RL J. Neurosci. 32:17909-17920(2012).
RN [4]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-268.
RX PubMed=24929359; DOI=10.1038/ncb2987;
RA Shen H., Giordano F., Wu Y., Chan J., Zhu C., Milosevic I., Wu X., Yao K.,
RA Chen B., Baumgart T., Sieburth D., De Camilli P.;
RT "Coupling between endocytosis and sphingosine kinase 1 recruitment.";
RL Nat. Cell Biol. 16:652-662(2014).
CC -!- FUNCTION: Catalyzes the phosphorylation of sphingosine to form
CC sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and
CC extracellular functions. Also acts on sphinganine (By similarity).
CC Required for neurotransmitter release from neuromuscular junctions.
CC Acts by recruiting the synaptic vesicle priming protein unc-13 to
CC synapses (PubMed:22588719, PubMed:23223309) (Probable).
CC {ECO:0000250|UniProtKB:Q9NYA1, ECO:0000269|PubMed:22588719,
CC ECO:0000269|PubMed:23223309, ECO:0000305|PubMed:24929359}.
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:0000305};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- SUBCELLULAR LOCATION: Presynaptic cell membrane
CC {ECO:0000269|PubMed:22588719, ECO:0000269|PubMed:23223309}. Cell
CC projection, axon {ECO:0000269|PubMed:24929359}. Perikaryon.
CC Mitochondrion membrane. Note=Recruitment to the presynaptic membrane
CC may be regulated by endogenous acetylcholine, which activates a
CC muscarinic signaling pathway acting through gar-3, egl-30 and unc-73.
CC Muscarinic-mediated recruitment of sphk-1 to presynaptic terminals
CC requires calcium influx and the calcium-binding protein calm-1.
CC Primarily observed on the outer surface of mitochondria in body wall
CC muscles. {ECO:0000269|PubMed:22588719, ECO:0000269|PubMed:23223309}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a;
CC IsoId=Q18425-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q18425-2; Sequence=VSP_045722;
CC Name=c;
CC IsoId=Q18425-3; Sequence=VSP_045721, VSP_045723;
CC Name=d;
CC IsoId=Q18425-4; Sequence=VSP_045720;
CC -!- TISSUE SPECIFICITY: Expressed in the majority of cholinergic and
CC GABAergic neurons, body wall muscle, excretory canal cells, intestine,
CC and hypodermis. {ECO:0000269|PubMed:22588719,
CC ECO:0000269|PubMed:23223309}.
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DR EMBL; Z66494; CAA91259.1; -; Genomic_DNA.
DR EMBL; Z66494; CAE48497.1; -; Genomic_DNA.
DR EMBL; Z66494; CBI83226.1; -; Genomic_DNA.
DR EMBL; Z66494; CCG28273.1; -; Genomic_DNA.
DR PIR; T19707; T19707.
DR RefSeq; NP_001022017.1; NM_001026846.1. [Q18425-1]
DR RefSeq; NP_001022018.1; NM_001026847.4.
DR RefSeq; NP_001254179.1; NM_001267250.1. [Q18425-3]
DR RefSeq; NP_001254180.1; NM_001267251.1. [Q18425-4]
DR AlphaFoldDB; Q18425; -.
DR SMR; Q18425; -.
DR STRING; 6239.C34C6.5a; -.
DR EPD; Q18425; -.
DR PaxDb; Q18425; -.
DR PeptideAtlas; Q18425; -.
DR EnsemblMetazoa; C34C6.5a.1; C34C6.5a.1; WBGene00007918. [Q18425-1]
DR EnsemblMetazoa; C34C6.5b.1; C34C6.5b.1; WBGene00007918. [Q18425-2]
DR EnsemblMetazoa; C34C6.5c.1; C34C6.5c.1; WBGene00007918. [Q18425-3]
DR EnsemblMetazoa; C34C6.5d.1; C34C6.5d.1; WBGene00007918. [Q18425-4]
DR GeneID; 183197; -.
DR KEGG; cel:CELE_C34C6.5; -.
DR UCSC; C34C6.5b.1; c. elegans.
DR CTD; 183197; -.
DR WormBase; C34C6.5a; CE03053; WBGene00007918; sphk-1. [Q18425-1]
DR WormBase; C34C6.5b; CE35833; WBGene00007918; sphk-1. [Q18425-2]
DR WormBase; C34C6.5c; CE44377; WBGene00007918; sphk-1. [Q18425-3]
DR WormBase; C34C6.5d; CE47276; WBGene00007918; sphk-1. [Q18425-4]
DR eggNOG; KOG1116; Eukaryota.
DR GeneTree; ENSGT00940000167991; -.
DR InParanoid; Q18425; -.
DR OMA; HYISIDG; -.
DR OrthoDB; 681139at2759; -.
DR PhylomeDB; Q18425; -.
DR Reactome; R-CEL-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-CEL-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-CEL-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-CEL-9009391; Extra-nuclear estrogen signaling.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q18425; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00007918; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0036062; C:presynaptic periactive zone; IDA:WormBase.
DR GO; GO:0016407; F:acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017050; F:D-erythro-sphingosine kinase activity; ISS:UniProtKB.
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:0046834; P:lipid phosphorylation; ISS:WormBase.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; IMP:WormBase.
DR GO; GO:0006473; P:protein acetylation; ISS:UniProtKB.
DR GO; GO:0040012; P:regulation of locomotion; IMP:WormBase.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
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 Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cell projection; Kinase;
KW Lipid metabolism; Membrane; Mitochondrion; Nucleotide-binding;
KW Reference proteome; Sphingolipid metabolism; Synapse; Transferase.
FT CHAIN 1..473
FT /note="Sphingosine kinase 1"
FT /id="PRO_0000421452"
FT DOMAIN 83..233
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT ACT_SITE 153
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 93..95
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 125..129
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 151..154
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 184..186
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 251
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 448..450
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT VAR_SEQ 1..135
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_045720"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_045721"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_045722"
FT VAR_SEQ 80..81
FT /note="PQ -> ME (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_045723"
FT MUTAGEN 151..155
FT /note="SGDGL->AAAAA: Impairs responsiveness to aldicarb,
FT probably due to loss of kinase function."
FT /evidence="ECO:0000269|PubMed:22588719"
FT MUTAGEN 184..187
FT /note="GSGN->DDDD: Impairs responsiveness to aldicarb,
FT probably due to loss of kinase function."
FT /evidence="ECO:0000269|PubMed:22588719"
FT MUTAGEN 268
FT /note="V->Q: Disrupts location in axons. Loss of
FT neurotransmission."
FT /evidence="ECO:0000269|PubMed:24929359"
FT MUTAGEN 271..272
FT /note="FI->AQ: Impairs translocation to the presynaptic
FT membrane."
FT /evidence="ECO:0000269|PubMed:22588719"
SQ SEQUENCE 473 AA; 52453 MW; DC9296EAD915103E CRC64;
MFIVVVTIFE NYTQWYSSLL TIFSLTIKRK LKTIRSMQDS TSKCTCTEHH MGGTICCCCR
SDAEENEQLT SVILSRKPPP QEQCRGNLLV FINPNSGTGK SLETFANTVG PKLDKSLIRY
EVVVTTGPNH ARNVLMTKAD LGKFNGVLIL SGDGLVFEAL NGILCREDAF RIFPTLPIGI
VPSGSGNGLL CSVLSKYGTK MNEKSVMERA LEIATSPTAK AESVALYSVK TDNQSYASFL
SIGWGLMADI DIDSEKWRKS LGHHRFTVMG FIRSCNLRSY KGRLTYRPYK PKGFHPSSNV
FSVYEKTTQQ RIDDSKVKTN GSVSDSEEET METKFQNWTL PDSDETLAVG SSDLEETVVI
EDNFVNIYAV TLSHIAADGP FAPSAKLEDN RIHLSYILWK DIGTRVNIAK YLLAIEHETH
LDLPFVKHVE VSSMKLEVIS EGSHVVLDGE VVDTKTIEVA STKNHISVFS STA
