MFS2B_MOUSE
ID MFS2B_MOUSE Reviewed; 494 AA.
AC Q3T9M1; Q3TRN2; Q3U198;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Sphingosine-1-phosphate transporter MFSD2B {ECO:0000305};
DE AltName: Full=Major facilitator superfamily domain-containing protein 2B {ECO:0000305};
DE Short=mMfsd2b {ECO:0000303|PubMed:29045386};
GN Name=Mfsd2b {ECO:0000303|PubMed:29045386, ECO:0000312|MGI:MGI:3583946};
GN Synonyms=Gm1964 {ECO:0000312|MGI:MGI:3583946};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=18694395; DOI=10.1042/bj20080165;
RA Angers M., Uldry M., Kong D., Gimble J.M., Jetten A.M.;
RT "Mfsd2a encodes a novel major facilitator superfamily domain-containing
RT protein highly induced in brown adipose tissue during fasting and adaptive
RT thermogenesis.";
RL Biochem. J. 416:347-355(2008).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=29045386; DOI=10.1038/nature24053;
RA Vu T.M., Ishizu A.N., Foo J.C., Toh X.R., Zhang F., Whee D.M., Torta F.,
RA Cazenave-Gassiot A., Matsumura T., Kim S., Toh S.E.S., Suda T.,
RA Silver D.L., Wenk M.R., Nguyen L.N.;
RT "Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes
RT and platelets.";
RL Nature 550:524-528(2017).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF ASP-85 AND LYS-413.
RX PubMed=29563527; DOI=10.1038/s41598-018-23300-x;
RA Kobayashi N., Kawasaki-Nishi S., Otsuka M., Hisano Y., Yamaguchi A.,
RA Nishi T.;
RT "MFSD2B is a sphingosine 1-phosphate transporter in erythroid cells.";
RL Sci. Rep. 8:4969-4969(2018).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-85 AND THR-147.
RX PubMed=33334894; DOI=10.1074/jbc.ra120.012941;
RA Nguyen T.Q., Vu T.M., Tukijan F., Muralidharan S., Foo J.C., Li Chin J.F.,
RA Hasan Z., Torta F., Nguyen L.N.;
RT "Erythrocytes efficiently utilize exogenous sphingosines for S1P synthesis
RT and export via Mfsd2b.";
RL J. Biol. Chem. 296:100201-100201(2021).
RN [6]
RP FUNCTION.
RX PubMed=33785361; DOI=10.1016/j.jbc.2021.100605;
RA Goto H., Miyamoto M., Kihara A.;
RT "Direct uptake of sphingosine-1-phosphate independent of phospholipid
RT phosphatases.";
RL J. Biol. Chem. 296:100605-100605(2021).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=33863882; DOI=10.1038/s41467-021-22642-x;
RA Chandrakanthan M., Nguyen T.Q., Hasan Z., Muralidharan S., Vu T.M.,
RA Li A.W.L., Le U.T.N., Thi Thuy Ha H., Baik S.H., Tan S.H., Foo J.C.,
RA Wenk M.R., Cazenave-Gassiot A., Torta F., Ong W.Y., Chan M.Y.Y.,
RA Nguyen L.N.;
RT "Deletion of Mfsd2b impairs thrombotic functions of platelets.";
RL Nat. Commun. 12:2286-2286(2021).
CC -!- FUNCTION: Lipid transporter that specifically mediates export of
CC sphingosine-1-phosphate in red blood cells and platelets
CC (PubMed:29045386, PubMed:29563527, PubMed:33334894, PubMed:33863882).
CC Sphingosine-1-phosphate is a signaling sphingolipid and its export from
CC red blood cells into in the plasma is required for red blood cell
CC morphology (PubMed:29045386). Sphingosine-1-phosphate export from
CC platelets is required for platelet aggregation and thrombus formation
CC (PubMed:33863882). Mediates the export of different sphingosine-1-
CC phosphate (S1P) species, including S1P(d18:0) (sphinganine 1-
CC phosphate), S1P (d18:1) (sphing-4-enine 1-phosphate) and S1P (d18:2)
CC (sphinga-4E,14Z-dienine-1-phosphate) (PubMed:33863882). Release of
CC sphingosine-1-phosphate is facilitated by a proton gradient
CC (PubMed:33334894). In contrast, cations, such as sodium, are not
CC required to drive sphingosine-1-phosphate transport (PubMed:29563527,
CC PubMed:33334894). In addition to export, also able to mediate S1P
CC import (PubMed:33785361). Does not transport lysophosphatidylcholine
CC (LPC) (PubMed:29045386). {ECO:0000269|PubMed:29045386,
CC ECO:0000269|PubMed:29563527, ECO:0000269|PubMed:33334894,
CC ECO:0000269|PubMed:33785361, ECO:0000269|PubMed:33863882}.
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:33334894, ECO:0000269|PubMed:33863882,
CC ECO:0000305|PubMed:29563527};
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:33863882};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinga-4E,14Z-dienine-1-phosphate(in) = sphinga-4E,14Z-
CC dienine-1-phosphate(out); Xref=Rhea:RHEA:70207, ChEBI:CHEBI:149632;
CC Evidence={ECO:0000269|PubMed:33863882};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29045386,
CC ECO:0000269|PubMed:29563527, ECO:0000269|PubMed:33863882}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localizes to the cell membrane and
CC intracellular membranes. {ECO:0000269|PubMed:29045386}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3T9M1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3T9M1-2; Sequence=VSP_034235;
CC Name=3;
CC IsoId=Q3T9M1-3; Sequence=VSP_034236, VSP_034237;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest expression in spleen,
CC lung and testis (PubMed:18694395). Predominantly expressed in erythroid
CC lineages giving rise to erythrocytes and platelets, but absent in
CC lymphoid lineages (PubMed:29045386, PubMed:29563527).
CC {ECO:0000269|PubMed:18694395, ECO:0000269|PubMed:29045386,
CC ECO:0000269|PubMed:29563527}.
CC -!- DISRUPTION PHENOTYPE: Mice were born with normal gross appearance and
CC thrived (PubMed:29045386). An accumulation of sphingosine-1-phosphate
CC in red blood cells is observed, while sphingosine-1-phosphate level in
CC plasma is significantly reduced (PubMed:29045386). Mice display
CC hemolysis associated with red blood cell stomatocytes, and the
CC hemolytic phenotype is severely increased with signs of membrane
CC fragility under stress erythropoiesis (PubMed:29045386). Mice
CC significantly reduced thrombus formation (PubMed:33863882).
CC {ECO:0000269|PubMed:29045386, ECO:0000269|PubMed:33863882}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE33602.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK156138; BAE33602.1; ALT_SEQ; mRNA.
DR EMBL; AK162620; BAE36995.1; -; mRNA.
DR EMBL; AK172423; BAE42999.1; -; mRNA.
DR CCDS; CCDS36401.2; -. [Q3T9M1-1]
DR AlphaFoldDB; Q3T9M1; -.
DR SMR; Q3T9M1; -.
DR STRING; 10090.ENSMUSP00000045315; -.
DR iPTMnet; Q3T9M1; -.
DR PhosphoSitePlus; Q3T9M1; -.
DR MaxQB; Q3T9M1; -.
DR PaxDb; Q3T9M1; -.
DR PRIDE; Q3T9M1; -.
DR ProteomicsDB; 292228; -. [Q3T9M1-1]
DR ProteomicsDB; 292229; -. [Q3T9M1-2]
DR ProteomicsDB; 292230; -. [Q3T9M1-3]
DR Antibodypedia; 47323; 94 antibodies from 21 providers.
DR Ensembl; ENSMUST00000085790; ENSMUSP00000082945; ENSMUSG00000037336. [Q3T9M1-3]
DR MGI; MGI:3583946; Mfsd2b.
DR VEuPathDB; HostDB:ENSMUSG00000037336; -.
DR eggNOG; KOG4830; Eukaryota.
DR GeneTree; ENSGT00390000005318; -.
DR HOGENOM; CLU_027408_6_2_1; -.
DR InParanoid; Q3T9M1; -.
DR PhylomeDB; Q3T9M1; -.
DR ChiTaRS; Mfsd2b; mouse.
DR PRO; PR:Q3T9M1; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q3T9M1; protein.
DR Bgee; ENSMUSG00000037336; Expressed in blood and 82 other tissues.
DR ExpressionAtlas; Q3T9M1; baseline and differential.
DR Genevisible; Q3T9M1; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0046624; F:sphingolipid transporter activity; IDA:UniProtKB.
DR GO; GO:0015293; F:symporter activity; IEA:InterPro.
DR GO; GO:0008643; P:carbohydrate transport; IEA:InterPro.
DR GO; GO:0006869; P:lipid transport; IDA:UniProtKB.
DR GO; GO:0071702; P:organic substance transport; IBA:GO_Central.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IDA:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR039672; MFS_2.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11328; PTHR11328; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Lipid transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..494
FT /note="Sphingosine-1-phosphate transporter MFSD2B"
FT /id="PRO_0000341261"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034235"
FT VAR_SEQ 345..347
FT /note="MVP -> CRV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034236"
FT VAR_SEQ 348..494
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034237"
FT MUTAGEN 85
FT /note="D->A: Decreased sphingosine-1-phosphate transport."
FT /evidence="ECO:0000269|PubMed:29563527,
FT ECO:0000269|PubMed:33334894"
FT MUTAGEN 147
FT /note="T->A: Decreased export of sphingosine-1-phosphate."
FT /evidence="ECO:0000269|PubMed:33334894"
FT MUTAGEN 413
FT /note="K->A: Decreased sphingosine-1-phosphate transport."
FT /evidence="ECO:0000269|PubMed:29563527"
FT CONFLICT 432
FT /note="C -> Y (in Ref. 1; BAE33602)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 494 AA; 52797 MW; A38A9828FE50AB4F CRC64;
MSVPHGPTPA PVAEPHTQEP GSDKRDGRLS VCTKVCYGIG GVPNQVASSA SAFYLQLFLL
DVAQIPAAQV SLALFGGKVS GAVADPVAGF FINKSRRTGS GRLMPWALGC MPLIALAYFF
LWFLPPFTSL RGLWYTSFYC LFQALATFFQ VPYTALTMIL TPSPRERDSA TAYRMTMEMA
GTLMGATVHG LIVSSAHGSQ RCEDTVHPRS PAVSPDVARL YCIAAAVVAL TYPVCGSLLC
LGVKEQPDTS APASGQGLNF FTGLAITSQH PPYLSLVVSF LFISAAVQVE QSYLVLFCTH
ASKLQDHVQN LVLIILVSAV LSTPLWEWVL QRFGKKTSAF GICVMVPFSI LLAAVPSAPV
AYVVAFVSGV SIAVSLLLPW SMLPDVVDDF QLQHRCGPGV ETIFYSSYVF FTKLSGAGAL
GISTLSLEFA GCEAGACQQA EEVVVTLKVL IGAVPTCMIL IGLCILLVGP TPKMPRQDTS
SQLSLRRRTS YSLA
