PCFT_XENLA
ID PCFT_XENLA Reviewed; 463 AA.
AC Q6DCX5;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Proton-coupled folate transporter {ECO:0000250|UniProtKB:Q96NT5};
DE AltName: Full=Heme carrier protein 1 {ECO:0000303|PubMed:16143108};
DE AltName: Full=Solute carrier family 46 member 1 {ECO:0000305};
GN Name=slc46a1 {ECO:0000250|UniProtKB:Q96NT5};
GN Synonyms=hcp1 {ECO:0000303|PubMed:16143108}, pcft;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=16143108; DOI=10.1016/j.cell.2005.06.025;
RA Shayeghi M., Latunde-Dada G.O., Oakhill J.S., Laftah A.H., Takeuchi K.,
RA Halliday N., Khan Y., Warley A., McCann F.E., Hider R.C., Frazer D.M.,
RA Anderson G.J., Vulpe C.D., Simpson R.J., McKie A.T.;
RT "Identification of an intestinal heme transporter.";
RL Cell 122:789-801(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). Also acts as a lower-affinity, pH-independent heme carrier
CC protein and constitutes the main importer of heme in the intestine
CC (PubMed:16143108). Imports heme in the retina and retinal pigment
CC epithelium, in neurons of the hippocampus, in hepatocytes and in the
CC renal epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q96NT5,
CC ECO:0000269|PubMed:16143108}.
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:F1NJ67}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96NT5};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q96NT5}; 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 -!- SIMILARITY: Belongs to the major facilitator superfamily. SLC46A
CC family. {ECO:0000305}.
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DR EMBL; BC077859; AAH77859.1; -; mRNA.
DR RefSeq; NP_001086984.2; NM_001093515.1.
DR AlphaFoldDB; Q6DCX5; -.
DR SMR; Q6DCX5; -.
DR PRIDE; Q6DCX5; -.
DR DNASU; 446819; -.
DR GeneID; 446819; -.
DR KEGG; xla:446819; -.
DR CTD; 446819; -.
DR Xenbase; XB-GENE-961471; slc46a1.L.
DR OrthoDB; 763423at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 446819; Expressed in kidney and 19 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; 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:0005542; F:folic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0015350; F:methotrexate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Disulfide bond; Endosome; Folate-binding;
KW Glycoprotein; Membrane; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..463
FT /note="Proton-coupled folate transporter"
FT /id="PRO_0000084855"
FT TOPO_DOM 1..27
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 28..46
FT /note="Helical; Name=TM1"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 47..86
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 87..112
FT /note="Helical; Name=TM2"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 113..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 117..139
FT /note="Helical; Name=TM3"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 140..144
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 145..158
FT /note="Helical; Name=TM4"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 159..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 182..207
FT /note="Helical; Name=TM5"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 208..212
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 213..231
FT /note="Helical; Name=TM6"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 232..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 271..293
FT /note="Helical; Name=TM7"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 294..306
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 307..329
FT /note="Helical; Name=TM8"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 330..335
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 336..355
FT /note="Helical; Name=TM9"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 356..359
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 360..380
FT /note="Helical; Name=TM10"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 381..392
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 393..418
FT /note="Helical; Name=TM11"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 419..426
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TRANSMEM 427..445
FT /note="Helical; Name=TM12"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT TOPO_DOM 446..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
FT BINDING 160
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 189
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 285
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 CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..302
FT /evidence="ECO:0000250|UniProtKB:F1NJ67"
SQ SEQUENCE 463 AA; 51200 MW; 85569AB7F2C8D5A1 CRC64;
MVSPDDSPEI RDRPRPRRCL LPASVTVEPV IFLSMFALAL QGPLATQYLW DRLSADIGFN
GTRTVGCAMN GSKSAGPEQQ EVETLTAHWS LYINLGGFLV GLFSVMLLGP WSDKVGRRPV
LMLPCIGLAL QAAVYLLVMY QELHVGYFLI GRFISGISGD FNMILAGCFA YIADVSDRQS
RTFRVAVLEA CLGIAGMVAS IIGGHWRKAQ GYINPFWLVF AVNLFTALYV YFCVEESVKD
KKPARLFTHR HYQSFFRLFT VQGENNRRRK LFLYSLALLV VVTVHMGAKN LFVLYELSYP
LCWDSDLIGY GSAAEHLTYL SSLAGLRLFQ LCLADSWVAE MGFISNISGL VVISLASTTP
IMFTGYGLRF FAMATTPVIR SKLSKMVEEG EQGALFSSVA CVEGLSFLLA TGLFNSLYPA
TLHFMKGFPF LLGALLLLIP AGIIGLIEVC EQKPMYSQFS EIS
