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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
 
 
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