SPNS2_DANRE
ID SPNS2_DANRE Reviewed; 504 AA.
AC A2SWM2; B9A1T2;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Sphingosine-1-phosphate transporter SPNS2 {ECO:0000305};
DE AltName: Full=Protein spinster homolog 2 {ECO:0000303|PubMed:19074308};
DE AltName: Full=Protein two of hearts {ECO:0000303|PubMed:19062281};
GN Name=spns2 {ECO:0000303|PubMed:19074308};
GN Synonyms=toh {ECO:0000303|PubMed:19062281};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19062281; DOI=10.1016/j.cub.2008.10.061;
RA Osborne N., Brand-Arzamendi K., Ober E.A., Jin S.-W., Verkade H.,
RA Holtzman N.G., Yelon D., Stainier D.Y.R.;
RT "The spinster homolog, two of hearts, is required for sphingosine 1-
RT phosphate signaling in zebrafish.";
RL Curr. Biol. 18:1882-1888(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF
RP ARG-153, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=19074308; DOI=10.1126/science.1167449;
RA Kawahara A., Nishi T., Hisano Y., Fukui H., Yamaguchi A., Mochizuki N.;
RT "The sphingolipid transporter spns2 functions in migration of zebrafish
RT myocardial precursors.";
RL Science 323:524-527(2009).
CC -!- FUNCTION: Lipid transporter that specifically mediates export of
CC sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and
CC sphinganine-1-phosphate, which play critical roles in regulating heart
CC development (PubMed:19062281, PubMed:19074308). Mediates the export of
CC S1P from cells in the extraembryonic yolk syncytial layer (YSL),
CC thereby regulating myocardial precursor migration (PubMed:19062281,
CC PubMed:19074308). {ECO:0000269|PubMed:19062281,
CC ECO:0000269|PubMed:19074308}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphing-4-enine 1-phosphate(in) = sphing-4-enine 1-
CC phosphate(out); Xref=Rhea:RHEA:38667, ChEBI:CHEBI:60119;
CC Evidence={ECO:0000250|UniProtKB:Q8IVW8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine 1-phosphate(in) = sphinganine 1-phosphate(out);
CC Xref=Rhea:RHEA:38671, ChEBI:CHEBI:57939;
CC Evidence={ECO:0000269|PubMed:19074308};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19074308};
CC Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000269|PubMed:19074308}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Induced at the marginal cells of the blastoderm at
CC dome stage. During gastrulation stages, it is predominantly expressed
CC in the extraembryonic yolk syncytial layer (YSL) with a dorsal-to-
CC ventral gradient. Expression in the YSL is strongly detected just below
CC the developing myocardial precursors and maintained throughout
CC segmentation period. This expression continues through early
CC somitogenesis. However, as somitogenesis proceeds, expression domains
CC become evident in the somitic mesoderm and in the endoderm adjacent to
CC the yolk extension. By 24 hpf, it is strongly expressed in a distinct
CC compartment of the somites, in the endoderm, and in the heart.
CC {ECO:0000269|PubMed:19062281, ECO:0000269|PubMed:19074308}.
CC -!- DISRUPTION PHENOTYPE: Disrupted formation of the primitive heart tube.
CC {ECO:0000269|PubMed:19062281}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Spinster (TC
CC 2.A.1.49) family. {ECO:0000305}.
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DR EMBL; DQ360111; ABC88833.1; -; mRNA.
DR EMBL; AB441164; BAH15191.1; -; mRNA.
DR RefSeq; NP_001077316.1; NM_001083847.1.
DR AlphaFoldDB; A2SWM2; -.
DR SMR; A2SWM2; -.
DR TCDB; 2.A.1.49.4; the major facilitator superfamily (mfs).
DR PaxDb; A2SWM2; -.
DR Ensembl; ENSDART00000153909; ENSDARP00000129119; ENSDARG00000061017.
DR GeneID; 568117; -.
DR KEGG; dre:568117; -.
DR CTD; 124976; -.
DR ZFIN; ZDB-GENE-030131-5843; spns2.
DR eggNOG; KOG1330; Eukaryota.
DR GeneTree; ENSGT00940000178429; -.
DR HOGENOM; CLU_001265_5_12_1; -.
DR InParanoid; A2SWM2; -.
DR OMA; WYVVVIC; -.
DR OrthoDB; 891881at2759; -.
DR PhylomeDB; A2SWM2; -.
DR Reactome; R-DRE-1660661; Sphingolipid de novo biosynthesis.
DR PRO; PR:A2SWM2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000061017; Expressed in spleen and 21 other tissues.
DR ExpressionAtlas; A2SWM2; baseline and differential.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046624; F:sphingolipid transporter activity; ISS:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IDA:ZFIN.
DR GO; GO:0003319; P:cardioblast migration to the midline involved in heart rudiment formation; IMP:ZFIN.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; IMP:ZFIN.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IGI:ZFIN.
DR GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR GO; GO:0061035; P:regulation of cartilage development; IMP:ZFIN.
DR GO; GO:0002920; P:regulation of humoral immune response; ISS:UniProtKB.
DR GO; GO:2000404; P:regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:ZFIN.
DR GO; GO:0001944; P:vasculature development; IGI:ZFIN.
DR CDD; cd17328; MFS_spinster_like; 1.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR044770; MFS_spinster-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR23505; PTHR23505; 1.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endosome; Lipid transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..504
FT /note="Sphingosine-1-phosphate transporter SPNS2"
FT /id="PRO_0000305045"
FT TRANSMEM 48..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 460..480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 153
FT /note="R->S: In ko157; displays cardia bifida (2 hearts)."
FT /evidence="ECO:0000269|PubMed:19074308"
FT CONFLICT 171
FT /note="I -> M (in Ref. 1; ABC88833)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 54670 MW; C91EA45455D654DE CRC64;
MCVESDGCEI EGCSSSDEVH TLSGSMSPAL KSRDLHHCRP GQKFHAALLR CRTPLVAAGI
LSFGNVLNYM DRYTVAGVLL DIQKQFKVGD SSAGLLQTVF ICSFMVAAPI FGYLGDRFNR
KIILSCGIFF WSAVTLLSSF ITKEYYWLLV LSRCLVGIGE SSYSSISPTI IGDLFTNNKR
TVMLSVFYLA IPLGSGLGYI LGSIAKDAGG HWYWALRVSP MLGLTAGTLI LIFVSEPKRG
SADQPGGRLK TRTSWVCDMK ALAKNRSYVF SSLASAAVSF ATGAFGIWIP QYLVRAQVVQ
KSAESCTYQP CSSRDSLIFG AITCVTGLLG VVIGAVTTRL CRQKTERADP LVCAVSMLGS
AIFICLIFVV AKKSIVGAYI CIFIGETLLF LNWAITADIL MYVVIPTRRA TAVAFQGFTS
HLLGDAGSPY LIGLISDSLQ ESYATSEIWQ FLSLGYALML CPFVIVLGGM FFLATALFFL
DDRDKAAKQV NQLARPPSTV KVTK