PCFT_BOVIN
ID PCFT_BOVIN Reviewed; 459 AA.
AC Q05B81; A1L0R5; A1L547;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Proton-coupled folate transporter {ECO:0000250|UniProtKB:Q96NT5};
DE AltName: Full=Heme carrier protein 1 {ECO:0000303|PubMed:17335806};
DE AltName: Full=Solute carrier family 46 member 1 {ECO:0000305};
GN Name=SLC46A1 {ECO:0000250|UniProtKB:Q96NT5};
GN Synonyms=HCP1 {ECO:0000303|PubMed:17335806},
GN PCFT {ECO:0000250|UniProtKB:Q96NT5};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Retinal pigment epithelium;
RX PubMed=17335806; DOI=10.1016/j.yexcr.2007.01.019;
RA Sharma S., Dimasi D., Broeer S., Kumar R., Della N.G.;
RT "Heme carrier protein 1 (HCP1) expression and functional analysis in the
RT retina and retinal pigment epithelium.";
RL Exp. Cell Res. 313:1251-1259(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-459.
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
CC -!- FUNCTION: Proton-coupled folate symporter that mediates folate
CC absorption using an H(+) gradient as a driving force (By similarity).
CC Involved in the intestinal absorption of folates at the brush-border
CC membrane of the proximal jejunum, and the transport from blood to
CC cerebrospinal fluid across the choroid plexus (By similarity).
CC Functions at acidic pH via alternate outward- and inward-open
CC conformation states (By similarity). Protonation of residues in the
CC outward open state primes the protein for transport (By similarity).
CC Binding of folate promotes breaking of salt bridge network and
CC subsequent closure of the extracellular gate, leading to the inward-
CC open state and release of protons and folate (By similarity). Also able
CC to transport antifolate drugs, such as methotrexate and pemetrexed (By
CC similarity). Involved in FOLR1-mediated endocytosis by serving as a
CC route of export of folates from acidified endosomes (By similarity).
CC Also acts as a lower-affinity, pH-independent heme carrier protein and
CC constitutes the main importer of heme in the intestine (By similarity).
CC Imports heme in the retina and retinal pigment epithelium, in neurons
CC of the hippocampus, in hepatocytes and in the renal epithelial cells
CC (PubMed:17335806). Hence, participates in the trafficking of heme and
CC increases intracellular iron content (By similarity).
CC {ECO:0000250|UniProtKB:Q96NT5, ECO:0000269|PubMed:17335806}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=folate(in) + H(+)(in) = folate(out) + H(+)(out);
CC Xref=Rhea:RHEA:70159, ChEBI:CHEBI:15378, ChEBI:CHEBI:62501;
CC Evidence={ECO:0000250|UniProtKB:Q96NT5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate(in) + H(+)(in) = (6S)-
CC 5-methyl-5,6,7,8-tetrahydrofolate(out) + H(+)(out);
CC Xref=Rhea:RHEA:70167, ChEBI:CHEBI:15378, ChEBI:CHEBI:18608;
CC Evidence={ECO:0000250|UniProtKB:Q6PEM8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + methotrexate(in) = H(+)(out) + methotrexate(out);
CC Xref=Rhea:RHEA:70163, ChEBI:CHEBI:15378, ChEBI:CHEBI:50681;
CC Evidence={ECO:0000250|UniProtKB:Q96NT5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + pemetrexed(in) = H(+)(out) + pemetrexed(out);
CC Xref=Rhea:RHEA:70171, ChEBI:CHEBI:15378, ChEBI:CHEBI:63724;
CC Evidence={ECO:0000250|UniProtKB:Q96NT5};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q96NT5}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96NT5};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000269|PubMed:17335806}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q96NT5}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:Q96NT5}; Multi-
CC pass membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6PEM8}. Note=Localizes to the apical membrane
CC of intestinal cells in iron-deficient cells, while it resides in the
CC cytoplasm in iron-replete cells (By similarity). Localizes to the
CC basolateral membrane of choroid plexus (By similarity).
CC {ECO:0000250|UniProtKB:Q6PEM8}.
CC -!- TISSUE SPECIFICITY: Expressed in retina and retinal pigment epithelium.
CC {ECO:0000269|PubMed:17335806}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. SLC46A
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABM06094.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY999968; AAY45892.1; -; mRNA.
DR EMBL; BC122640; AAI22641.1; -; mRNA.
DR EMBL; BT029834; ABM06094.1; ALT_INIT; mRNA.
DR RefSeq; NP_001073053.1; NM_001079585.1.
DR AlphaFoldDB; Q05B81; -.
DR SMR; Q05B81; -.
DR STRING; 9913.ENSBTAP00000035161; -.
DR PaxDb; Q05B81; -.
DR Ensembl; ENSBTAT00000035283; ENSBTAP00000035161; ENSBTAG00000002817.
DR GeneID; 511097; -.
DR KEGG; bta:511097; -.
DR CTD; 113235; -.
DR VEuPathDB; HostDB:ENSBTAG00000002817; -.
DR VGNC; VGNC:34884; SLC46A1.
DR eggNOG; KOG2816; Eukaryota.
DR GeneTree; ENSGT00950000183096; -.
DR HOGENOM; CLU_028365_1_0_1; -.
DR InParanoid; Q05B81; -.
DR OMA; SPRANDE; -.
DR OrthoDB; 763423at2759; -.
DR TreeFam; TF315701; -.
DR Reactome; R-BTA-196757; Metabolism of folate and pterines.
DR Reactome; R-BTA-917937; Iron uptake and transport.
DR Reactome; R-BTA-9707616; Heme signaling.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000002817; Expressed in duodenum and 104 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0005542; F:folic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0008517; F:folic acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0140211; F:folic acid:proton symporter activity; IEA:Ensembl.
DR GO; GO:0015232; F:heme transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015350; F:methotrexate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:1904447; P:folate import across plasma membrane; IEA:Ensembl.
DR GO; GO:0015884; P:folic acid transport; ISS:UniProtKB.
DR GO; GO:0015886; P:heme transport; IDA:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell membrane; Cytoplasm; Disulfide bond; Endosome;
KW Folate-binding; Glycoprotein; Membrane; Phosphoprotein; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..459
FT /note="Proton-coupled folate transporter"
FT /id="PRO_0000291649"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 26..44
FT /note="Helical; Name=TM1"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 45..82
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 83..108
FT /note="Helical; Name=TM2"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 109..112
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 113..135
FT /note="Helical; Name=TM3"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 136..140
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 141..154
FT /note="Helical; Name=TM4"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 155..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 178..203
FT /note="Helical; Name=TM5"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 204..208
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 209..227
FT /note="Helical; Name=TM6"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 228..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 267..289
FT /note="Helical; Name=TM7"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 290..302
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 303..325
FT /note="Helical; Name=TM8"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 326..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 332..351
FT /note="Helical; Name=TM9"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 352..355
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 356..376
FT /note="Helical; Name=TM10"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 377..388
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 389..414
FT /note="Helical; Name=TM11"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 415..422
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 423..441
FT /note="Helical; Name=TM12"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 442..459
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT BINDING 156
FT /ligand="H(+)"
FT /ligand_id="ChEBI:CHEBI:15378"
FT /note="reversibly protonated residue during proton
FT transport"
FT /evidence="ECO:0000250|UniProtKB:Q96NT5"
FT BINDING 185
FT /ligand="H(+)"
FT /ligand_id="ChEBI:CHEBI:15378"
FT /note="reversibly protonated residue during proton
FT transport"
FT /evidence="ECO:0000250|UniProtKB:Q96NT5"
FT BINDING 281
FT /ligand="H(+)"
FT /ligand_id="ChEBI:CHEBI:15378"
FT /note="reversibly protonated residue during proton
FT transport"
FT /evidence="ECO:0000250|UniProtKB:Q96NT5"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q96NT5"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96NT5"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 66..298
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT CONFLICT 2
FT /note="E -> K (in Ref. 1; AAY45892)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="P -> S (in Ref. 1; AAY45892)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="A -> T (in Ref. 1; AAY45892 and 3; ABM06094)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="V -> I (in Ref. 1; AAY45892)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="Q -> H (in Ref. 1; AAY45892)"
FT /evidence="ECO:0000305"
FT CONFLICT 429
FT /note="A -> G (in Ref. 1; AAY45892 and 3; ABM06094)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 50428 MW; 6468953BC5F14D85 CRC64;
MEGRANSPGE PRAWPTRSVL CRGCVEPLVF LANFALVLQG PVTTQYLWHR FSADLGYNGT
RHRDSCSNHS VDPIAQEVET LTSHWTLYMN VGGFLVGLFS STLLGAWSDC VGRRPLLVLA
SLGLLLQTVL SIFVVQLHLH IGYLVLGRIL CALLGDFSGL LAASFASVAD VSSSRTRTIR
MALLEACIGV AGMLASFIGG FLLQEQVYVN PFWLALAVLT VMTLYAAFCF GETVKERTPT
RLFTLRHHRS VIQLYVTQAP EKSRKHLALY SLAIFVMITV HLGAQDILTL YELSAPLCWD
SRLISYGSAA QQLPYLTSLL GLRLLQYCLA DTWVAEIGLV FNILGMMVFA FATITPLMFT
GYGLLFLSLV VTPIIRAKLS RLVRQSEQGA LFSALACVNG LAMLMASGIF NSLYPATLNL
MKGFPFLLAA GLLFIPAILM GILERDNHCP EFQEFSQSP
