SPNS2_HUMAN
ID SPNS2_HUMAN Reviewed; 549 AA.
AC Q8IVW8; B9A1T3;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Sphingosine-1-phosphate transporter SPNS2 {ECO:0000305};
DE AltName: Full=Protein spinster homolog 2 {ECO:0000305};
GN Name=SPNS2 {ECO:0000303|PubMed:19074308, ECO:0000312|HGNC:HGNC:26992};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-549, FUNCTION, AND MUTAGENESIS OF ARG-200.
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).
RN [3]
RP FUNCTION.
RX PubMed=21084291; DOI=10.1074/jbc.m110.171116;
RA Hisano Y., Kobayashi N., Kawahara A., Yamaguchi A., Nishi T.;
RT "The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter
RT of the phosphorylated form of the immunomodulating agent FTY720.";
RL J. Biol. Chem. 286:1758-1766(2011).
RN [4]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=23180825; DOI=10.1096/fj.12-219618;
RA Nagahashi M., Kim E.Y., Yamada A., Ramachandran S., Allegood J.C.,
RA Hait N.C., Maceyka M., Milstien S., Takabe K., Spiegel S.;
RT "Spns2, a transporter of phosphorylated sphingoid bases, regulates their
RT blood and lymph levels, and the lymphatic network.";
RL FASEB J. 27:1001-1011(2013).
RN [5]
RP INVOLVEMENT IN DFNB115, FUNCTION, AND VARIANT DFNB115 SER-319 DEL.
RX PubMed=30973865; DOI=10.1371/journal.pbio.3000194;
RA Ingham N.J., Pearson S.A., Vancollie V.E., Rook V., Lewis M.A., Chen J.,
RA Buniello A., Martelletti E., Preite L., Lam C.C., Weiss F.D., Powis Z.,
RA Suwannarat P., Lelliott C.J., Dawson S.J., White J.K., Steel K.P.;
RT "Mouse screen reveals multiple new genes underlying mouse and human hearing
RT loss.";
RL PLoS Biol. 17:E3000194-E3000194(2019).
CC -!- FUNCTION: Lipid transporter that specifically mediates export of
CC sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and
CC sphinganine-1-phosphate in the lymph, thereby playing a role in
CC lymphocyte trafficking (PubMed:19074308, PubMed:23180825,
CC PubMed:21084291). S1P is a bioactive signaling molecule that regulates
CC many physiological processes important for the development and for the
CC immune system (PubMed:19074308, PubMed:23180825). Regulates levels of
CC S1P and the S1P gradient that exists between the high circulating
CC concentrations of S1P and low tissue levels that control lymphocyte
CC trafficking (PubMed:19074308, PubMed:23180825). Required for the egress
CC of T-cells from lymph nodes during an immune response by mediating S1P
CC secretion, which generates a gradient that enables activated T-cells to
CC access lymph (By similarity). Also required for the egress of immature
CC B-cells from the bone marrow (By similarity). In contrast, not involved
CC in S1P release from red blood cells (By similarity). Involved in
CC auditory function (PubMed:30973865). S1P release in the inner ear is
CC required for maintenance of the endocochlear potential in the cochlea
CC (By similarity). In addition to export, also able to mediate S1P import
CC (By similarity). {ECO:0000250|UniProtKB:Q91VM4,
CC ECO:0000269|PubMed:19074308, ECO:0000269|PubMed:21084291,
CC ECO:0000269|PubMed:23180825, ECO:0000269|PubMed:30973865}.
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:0000269|PubMed:23180825};
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:23180825};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:A2SWM2};
CC Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:A2SWM2}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISEASE: Deafness, autosomal recessive, 115 (DFNB115) [MIM:618457]: A
CC form of non-syndromic deafness characterized by severe sensorineural
CC hearing impairment in early childhood. Sensorineural deafness results
CC from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:30973865}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Spinster (TC
CC 2.A.1.49) family. {ECO:0000305}.
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DR EMBL; BC041772; AAH41772.2; -; mRNA.
DR EMBL; AB441165; BAH15192.1; -; mRNA.
DR CCDS; CCDS42237.1; -.
DR RefSeq; NP_001118230.1; NM_001124758.2.
DR AlphaFoldDB; Q8IVW8; -.
DR SMR; Q8IVW8; -.
DR BioGRID; 125907; 3.
DR STRING; 9606.ENSP00000333292; -.
DR SwissLipids; SLP:000000351; -.
DR TCDB; 2.A.1.49.6; the major facilitator superfamily (mfs).
DR iPTMnet; Q8IVW8; -.
DR PhosphoSitePlus; Q8IVW8; -.
DR BioMuta; SPNS2; -.
DR DMDM; 121947811; -.
DR EPD; Q8IVW8; -.
DR jPOST; Q8IVW8; -.
DR MassIVE; Q8IVW8; -.
DR PaxDb; Q8IVW8; -.
DR PeptideAtlas; Q8IVW8; -.
DR PRIDE; Q8IVW8; -.
DR ProteomicsDB; 70788; -.
DR Antibodypedia; 42673; 125 antibodies from 19 providers.
DR DNASU; 124976; -.
DR Ensembl; ENST00000329078.8; ENSP00000333292.3; ENSG00000183018.9.
DR GeneID; 124976; -.
DR KEGG; hsa:124976; -.
DR MANE-Select; ENST00000329078.8; ENSP00000333292.3; NM_001124758.3; NP_001118230.1.
DR UCSC; uc002fxx.3; human.
DR CTD; 124976; -.
DR DisGeNET; 124976; -.
DR GeneCards; SPNS2; -.
DR HGNC; HGNC:26992; SPNS2.
DR HPA; ENSG00000183018; Tissue enhanced (esophagus).
DR MalaCards; SPNS2; -.
DR MIM; 612584; gene.
DR MIM; 618457; phenotype.
DR neXtProt; NX_Q8IVW8; -.
DR OpenTargets; ENSG00000183018; -.
DR PharmGKB; PA162404590; -.
DR VEuPathDB; HostDB:ENSG00000183018; -.
DR eggNOG; KOG1330; Eukaryota.
DR GeneTree; ENSGT00390000005976; -.
DR HOGENOM; CLU_001265_5_12_1; -.
DR InParanoid; Q8IVW8; -.
DR OMA; WYVVVIC; -.
DR OrthoDB; 891881at2759; -.
DR PhylomeDB; Q8IVW8; -.
DR TreeFam; TF314395; -.
DR PathwayCommons; Q8IVW8; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 124976; 13 hits in 1062 CRISPR screens.
DR ChiTaRS; SPNS2; human.
DR GenomeRNAi; 124976; -.
DR Pharos; Q8IVW8; Tbio.
DR PRO; PR:Q8IVW8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IVW8; protein.
DR Bgee; ENSG00000183018; Expressed in lower esophagus mucosa and 154 other tissues.
DR ExpressionAtlas; Q8IVW8; baseline and differential.
DR Genevisible; Q8IVW8; HS.
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; TAS:Reactome.
DR GO; GO:0046624; F:sphingolipid transporter activity; IDA:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0006869; P:lipid transport; IDA:UniProtKB.
DR GO; GO:0048535; P:lymph node development; IEA:Ensembl.
DR GO; GO:0072676; P:lymphocyte migration; IEA:Ensembl.
DR GO; GO:0048073; P:regulation of eye pigmentation; IEA:Ensembl.
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:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
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; Deafness; Disease variant; Endosome; Lipid transport;
KW Membrane; Non-syndromic deafness; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..549
FT /note="Sphingosine-1-phosphate transporter SPNS2"
FT /id="PRO_0000305043"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 398..418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 466..486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 507..527
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 14..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 319
FT /note="Missing (in DFNB115; unknown pathological
FT significance; dbSNP:rs749994718)"
FT /evidence="ECO:0000269|PubMed:30973865"
FT /id="VAR_082112"
FT MUTAGEN 200
FT /note="R->S: Loss of function; does not rescue the cardia
FT bifida phenotype in the morpholino knockdown in zebrafish."
FT /evidence="ECO:0000269|PubMed:19074308"
FT CONFLICT 74
FT /note="T -> A (in Ref. 2; BAH15192)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 549 AA; 58044 MW; 379483F11F2C4D01 CRC64;
MMCLECASAA AGGAEEEEAD AERRRRRRGA QRGAGGSGCC GARGAGGAGV SAAGDEVQTL
SGSVRRAPTG PPGTPGTPGC AATAKGPGAQ QPKPASLGRG RGAAAAILSL GNVLNYLDRY
TVAGVLLDIQ QHFGVKDRGA GLLQSVFICS FMVAAPIFGY LGDRFNRKVI LSCGIFFWSA
VTFSSSFIPQ QYFWLLVLSR GLVGIGEASY STIAPTIIGD LFTKNTRTLM LSVFYFAIPL
GSGLGYITGS SVKQAAGDWH WALRVSPVLG MITGTLILIL VPATKRGHAD QLGDQLKART
SWLRDMKALI RNRSYVFSSL ATSAVSFATG ALGMWIPLYL HRAQVVQKTA ETCNSPPCGA
KDSLIFGAIT CFTGFLGVVT GAGATRWCRL KTQRADPLVC AVGMLGSAIF ICLIFVAAKS
SIVGAYICIF VGETLLFSNW AITADILMYV VIPTRRATAV ALQSFTSHLL GDAGSPYLIG
FISDLIRQST KDSPLWEFLS LGYALMLCPF VVVLGGMFFL ATALFFVSDR ARAEQQVNQL
AMPPASVKV
