MFS2B_HUMAN
ID MFS2B_HUMAN Reviewed; 504 AA.
AC A6NFX1; B5MC32; J3KNU6;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 4.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Sphingosine-1-phosphate transporter MFSD2B {ECO:0000305};
DE AltName: Full=Major facilitator superfamily domain-containing protein 2B {ECO:0000305};
DE Short=hMfsd2b {ECO:0000303|PubMed:29045386};
GN Name=MFSD2B {ECO:0000303|PubMed:29045386, ECO:0000312|HGNC:HGNC:37207};
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-271.
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION.
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-95; THR-157 AND
RP LYS-423.
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 [5]
RP SUBCELLULAR LOCATION, FUNCTION, AND CATALYTIC ACTIVITY.
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).
CC -!- FUNCTION: Lipid transporter that specifically mediates export of
CC sphingosine-1-phosphate in red blood cells and platelets
CC (PubMed:29045386). Sphingosine-1-phosphate is a signaling sphingolipid
CC and its export from red blood cells into in the plasma is required for
CC red blood cell morphology (By similarity). Sphingosine-1-phosphate
CC export from platelets is required for platelet aggregation and thrombus
CC formation (By similarity). Mediates the export of different
CC sphingosine-1-phosphate (S1P) species, including S1P(d18:0)
CC (sphinganine 1-phosphate), S1P (d18:1) (sphing-4-enine 1-phosphate) and
CC S1P (d18:2) (sphinga-4E,14Z-dienine-1-phosphate) (Probable). Release of
CC sphingosine-1-phosphate is facilitated by a proton gradient (By
CC similarity). In contrast, cations, such as sodium, are not required to
CC drive sphingosine-1-phosphate transport (Probable). In addition to
CC export, also able to mediate S1P import (By similarity). Does not
CC transport lysophosphatidylcholine (LPC) (Probable).
CC {ECO:0000250|UniProtKB:Q3T9M1, ECO:0000269|PubMed:29045386,
CC ECO:0000305|PubMed:29563527}.
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: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:0000250|UniProtKB:Q3T9M1};
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:0000250|UniProtKB:Q3T9M1};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29045386,
CC ECO:0000269|PubMed:29563527}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to the cell membrane and intracellular
CC membranes. {ECO:0000269|PubMed:29045386}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; AC104665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX357394; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS86824.1; -.
DR RefSeq; NP_001333809.1; NM_001346880.1.
DR AlphaFoldDB; A6NFX1; -.
DR SMR; A6NFX1; -.
DR BioGRID; 132904; 1.
DR IntAct; A6NFX1; 1.
DR STRING; 9606.ENSP00000385527; -.
DR TCDB; 2.A.2.3.16; the glycoside-pentoside-hexuronide (gph):cation symporter family.
DR GlyGen; A6NFX1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A6NFX1; -.
DR PhosphoSitePlus; A6NFX1; -.
DR BioMuta; MFSD2B; -.
DR MassIVE; A6NFX1; -.
DR PaxDb; A6NFX1; -.
DR PeptideAtlas; A6NFX1; -.
DR PRIDE; A6NFX1; -.
DR ProteomicsDB; 1085; -.
DR Antibodypedia; 47323; 94 antibodies from 21 providers.
DR DNASU; 388931; -.
DR Ensembl; ENST00000338315.6; ENSP00000342501.4; ENSG00000205639.12.
DR GeneID; 388931; -.
DR KEGG; hsa:388931; -.
DR MANE-Select; ENST00000338315.6; ENSP00000342501.4; NM_001346880.2; NP_001333809.1.
DR UCSC; uc032ngs.2; human.
DR CTD; 388931; -.
DR DisGeNET; 388931; -.
DR GeneCards; MFSD2B; -.
DR HGNC; HGNC:37207; MFSD2B.
DR HPA; ENSG00000205639; Tissue enriched (bone).
DR MIM; 617845; gene.
DR neXtProt; NX_A6NFX1; -.
DR OpenTargets; ENSG00000205639; -.
DR PharmGKB; PA165696804; -.
DR VEuPathDB; HostDB:ENSG00000205639; -.
DR eggNOG; KOG4830; Eukaryota.
DR GeneTree; ENSGT00390000005318; -.
DR HOGENOM; CLU_027408_6_1_1; -.
DR InParanoid; A6NFX1; -.
DR OMA; LPMAEWF; -.
DR OrthoDB; 827101at2759; -.
DR PhylomeDB; A6NFX1; -.
DR TreeFam; TF331194; -.
DR PathwayCommons; A6NFX1; -.
DR BioGRID-ORCS; 388931; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; MFSD2B; human.
DR GenomeRNAi; 388931; -.
DR Pharos; A6NFX1; Tdark.
DR PRO; PR:A6NFX1; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; A6NFX1; protein.
DR Bgee; ENSG00000205639; Expressed in blood and 101 other tissues.
DR ExpressionAtlas; A6NFX1; baseline and differential.
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; ISS:UniProtKB.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISS: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 Cell membrane; Lipid transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..504
FT /note="Sphingosine-1-phosphate transporter MFSD2B"
FT /id="PRO_0000341260"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 95
FT /note="D->A: Abolishes export of sphingosine-1-phosphate."
FT /evidence="ECO:0000269|PubMed:29045386"
FT MUTAGEN 157
FT /note="T->A: Abolishes export of sphingosine-1-phosphate."
FT /evidence="ECO:0000269|PubMed:29045386"
FT MUTAGEN 423
FT /note="K->A: Does not affect export of sphingosine-1-
FT phosphate."
FT /evidence="ECO:0000269|PubMed:29045386"
SQ SEQUENCE 504 AA; 53743 MW; 22812066AECE07B8 CRC64;
MAAPPAPAAK GSPQPEPHAP EPGPGSAKRG REDSRAGRLS FCTKVCYGIG GVPNQIASSA
TAFYLQLFLL DIAQIPAAQV SLVLFGGKVS GAAADPVAGF FINRSQRTGS GRLMPWVLGC
TPFIALAYFF LWFLPPFTSL RGLWYTTFYC LFQALATFFQ VPYTALTMLL TPCPRERDSA
TAYRMTVEMA GTLMGATVHG LIVSGAHRPH RCEATATPGP VTVSPNAAHL YCIAAAVVVV
TYPVCISLLC LGVKERPDPS APASGPGLSF LAGLSLTTRH PPYLKLVISF LFISAAVQVE
QSYLVLFCTH ASQLHDHVQG LVLTVLVSAV LSTPLWEWVL QRFGKKTSAF GIFAMVPFAI
LLAAVPTAPV AYVVAFVSGV SIAVSLLLPW SMLPDVVDDF QLQHRHGPGL ETIFYSSYVF
FTKLSGACAL GISTLSLEFS GYKAGVCKQA EEVVVTLKVL IGAVPTCMIL AGLCILMVGS
TPKTPSRDAS SRLSLRRRTS YSLA
