FLVC1_MOUSE
ID FLVC1_MOUSE Reviewed; 560 AA.
AC B2RXV4;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Feline leukemia virus subgroup C receptor-related protein 1;
DE Short=Feline leukemia virus subgroup C receptor;
DE AltName: Full=Major facilitator superfamily domain containing 7B;
DE Short=Mfsd7b;
GN Name=Flvcr1; Synonyms=Mfsd7b;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP FUNCTION (ISOFORM 1), AND DISRUPTION PHENOTYPE.
RX PubMed=18258918; DOI=10.1126/science.1151133;
RA Keel S.B., Doty R.T., Yang Z., Quigley J.G., Chen J., Knoblaugh S.,
RA Kingsley P.D., De Domenico I., Vaughn M.B., Kaplan J., Palis J.,
RA Abkowitz J.L.;
RT "A heme export protein is required for red blood cell differentiation and
RT iron homeostasis.";
RL Science 319:825-828(2008).
RN [4]
RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), SUBCELLULAR
RP LOCATION (ISOFORM 2), AND DISRUPTION PHENOTYPE.
RX PubMed=23187127; DOI=10.1172/jci62422;
RA Chiabrando D., Marro S., Mercurio S., Giorgi C., Petrillo S., Vinchi F.,
RA Fiorito V., Fagoonee S., Camporeale A., Turco E., Merlo G.R., Silengo L.,
RA Altruda F., Pinton P., Tolosano E.;
RT "The mitochondrial heme exporter FLVCR1b mediates erythroid
RT differentiation.";
RL J. Clin. Invest. 122:4569-4579(2012).
CC -!- FUNCTION: [Isoform 1]: Heme transporter that exports cytoplasmic heme.
CC It can also export coproporphyrin and protoporphyrin IX, which are both
CC intermediate products in the heme biosynthetic pathway. Does not export
CC bilirubin. Heme export depends on the presence of HPX and is required
CC to maintain intracellular free heme balance, protecting cells from heme
CC toxicity. Heme export provides protection from heme or ferrous iron
CC toxicities in liver, brain, sensory neurons and during erythtopoiesis,
CC a process in which heme synthesis intensifies. Causes susceptibility to
CC FeLV-C in vitro. {ECO:0000250|UniProtKB:Q9Y5Y0,
CC ECO:0000269|PubMed:18258918}.
CC -!- FUNCTION: [Isoform 2]: Heme transporter that promotes heme efflux from
CC the mitochondrion to the cytoplasm. Essential for erythroid
CC differentiation.
CC -!- SUBUNIT: Interacts with HPX. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250}; Multi-
CC pass membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion membrane
CC {ECO:0000269|PubMed:23187127}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23187127}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Flvcr1a;
CC IsoId=B2RXV4-1; Sequence=Displayed;
CC Name=2; Synonyms=Flvcr1b, mitochondrial;
CC IsoId=B2RXV4-2; Sequence=VSP_047867;
CC -!- PTM: N-Glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Lack definitive erythropoiesis, have craniofacial
CC and limb deformities, and die in midgestation. Mice with FLVCR1 that is
CC deleted neonatally develop a severe macrocytic anemia with
CC proerythroblast maturation arrest. Mice lacking the plasma membrane
CC isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but
CC exhibited hemorrhages, edema, and skeletal abnormalities.
CC {ECO:0000269|PubMed:18258918, ECO:0000269|PubMed:23187127}.
CC -!- MISCELLANEOUS: [Isoform 2]: Has a probable mitochondrial transit
CC peptide at positions 1-38. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Feline
CC leukemia virus subgroup C receptor (TC 2.A.1.28.1) family.
CC {ECO:0000305}.
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DR EMBL; AC138229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC157992; AAI57993.1; -; mRNA.
DR CCDS; CCDS35823.1; -. [B2RXV4-1]
DR RefSeq; NP_001074728.1; NM_001081259.1. [B2RXV4-1]
DR RefSeq; NP_001300676.1; NM_001313747.1.
DR AlphaFoldDB; B2RXV4; -.
DR SMR; B2RXV4; -.
DR STRING; 10090.ENSMUSP00000082777; -.
DR GlyGen; B2RXV4; 1 site.
DR iPTMnet; B2RXV4; -.
DR PhosphoSitePlus; B2RXV4; -.
DR EPD; B2RXV4; -.
DR MaxQB; B2RXV4; -.
DR PaxDb; B2RXV4; -.
DR PeptideAtlas; B2RXV4; -.
DR PRIDE; B2RXV4; -.
DR ProteomicsDB; 267365; -. [B2RXV4-1]
DR ProteomicsDB; 267366; -. [B2RXV4-2]
DR Antibodypedia; 20720; 180 antibodies from 32 providers.
DR Ensembl; ENSMUST00000085635; ENSMUSP00000082777; ENSMUSG00000066595. [B2RXV4-1]
DR GeneID; 226844; -.
DR KEGG; mmu:226844; -.
DR UCSC; uc007ebv.1; mouse. [B2RXV4-1]
DR UCSC; uc011wyn.1; mouse. [B2RXV4-2]
DR CTD; 28982; -.
DR MGI; MGI:2444881; Flvcr1.
DR VEuPathDB; HostDB:ENSMUSG00000066595; -.
DR eggNOG; KOG2563; Eukaryota.
DR GeneTree; ENSGT01030000234625; -.
DR HOGENOM; CLU_023132_0_0_1; -.
DR InParanoid; B2RXV4; -.
DR OMA; TYYKGEE; -.
DR OrthoDB; 702737at2759; -.
DR PhylomeDB; B2RXV4; -.
DR TreeFam; TF314292; -.
DR Reactome; R-MMU-189451; Heme biosynthesis.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 226844; 14 hits in 78 CRISPR screens.
DR ChiTaRS; Flvcr1; mouse.
DR PRO; PR:B2RXV4; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; B2RXV4; protein.
DR Bgee; ENSMUSG00000066595; Expressed in epithelium of small intestine and 215 other tissues.
DR ExpressionAtlas; B2RXV4; baseline and differential.
DR Genevisible; B2RXV4; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0015232; F:heme transmembrane transporter activity; ISO:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:MGI.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW.
DR GO; GO:0060323; P:head morphogenesis; IMP:MGI.
DR GO; GO:0097037; P:heme export; ISO:MGI.
DR GO; GO:0015886; P:heme transport; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0035108; P:limb morphogenesis; IMP:MGI.
DR GO; GO:0006839; P:mitochondrial transport; ISO:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0046620; P:regulation of organ growth; IMP:MGI.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Erythrocyte maturation; Glycoprotein;
KW Membrane; Mitochondrion; Phosphoprotein; Receptor; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..560
FT /note="Feline leukemia virus subgroup C receptor-related
FT protein 1"
FT /id="PRO_0000423424"
FT TOPO_DOM 1..100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..121
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 122..140
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..192
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..280
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 358..377
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..406
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 428..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 451..464
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 486..496
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..560
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5Y0"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..281
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_047867"
SQ SEQUENCE 560 AA; 60469 MW; 2FD8691D8E55BE52 CRC64;
MARPDDEVGP AVAPGHPLGK GYLPVPKGAP DGEARLVPQN GPEALNGGPG LGPLIAGAQG
GPQALIAAEE ETQARLLPAG DGEDVPCPAC PPRTALSPRR FVVLLIFSLY SLVNAFQWIQ
YSSISNVFED FYEVSPLHIN WLSMVYMVAY VPLIFPATWL LDTRGLRLTA LLGSGLNCLG
AWVKCGSVQR HLFWVTMLGQ ILCSVAQVFI LGLPSPVASV WFGPKEVSTA CATAVLGNQL
GTAVGFLLPP VLVPALGTQN STGLLAHTQN NTDLLAHNIN TMFYGTAFIS TFLFFLTIIA
FKEKPPLPPS QAQAVLRDSP PEEYSYKSSI WNLCRNIPFV LLLVSYGIMT GAFYSISTLL
NQIILTYYVG EEVNAGRIGL TLVVAGMVGS ILCGLWLDYT KTYKQTTLIV YVLSFIGMLI
FTFTLNLGYI IVVFFTGGIL GFFMTGYLPL GFEFAVEITY PESEGMSSGL LNTAAQILGI
FFTLAQGKIT TDYNSPEAGN IFLCAWMFVG IILTALIKSD LRRHNINTGL TNIDVKAVPV
DSRVDPKPKV MVSIQSESSL
