S19A1_RAT
ID S19A1_RAT Reviewed; 512 AA.
AC Q62866; D3ZQS7; Q9QUM8;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Reduced folate transporter {ECO:0000305};
DE AltName: Full=Methotrexate carrier 1 {ECO:0000303|PubMed:10827155};
DE Short=MTX-1 {ECO:0000303|PubMed:10827155};
DE Short=MTX1 {ECO:0000303|PubMed:10827155};
DE AltName: Full=Plasma membrane folate antiporter SLC19A1 {ECO:0000305};
DE AltName: Full=Reduced folate carrier 1 {ECO:0000303|Ref.2};
DE Short=RFC-1 {ECO:0000303|Ref.2};
DE Short=RFC1 {ECO:0000303|Ref.2};
DE AltName: Full=Solute carrier family 19 member 1 {ECO:0000305};
GN Name=Slc19a1 {ECO:0000312|RGD:3695};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=10827155; DOI=10.1053/jhep.2000.7478;
RA Honscha W., Doetsch K.U., Thomsen N., Petzinger E.;
RT "Cloning and functional characterization of the bile acid-sensitive
RT methotrexate carrier from rat liver cells.";
RL Hepatology 31:1296-1304(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Aorta;
RA Rubin S.A., Dyer D.L., Sharifi B.G., Said H.M.;
RT "Cloning and expression of a reduced folate carrier in rat vascular smooth
RT muscle.";
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [6]
RP FUNCTION.
RX PubMed=11600421; DOI=10.1152/ajpcell.2001.281.5.c1579;
RA Rajgopal A., Sierra E.E., Zhao R., Goldman I.D.;
RT "Expression of the reduced folate carrier SLC19A1 in IEC-6 cells results in
RT two distinct transport activities.";
RL Am. J. Physiol. 281:C1579-C1586(2001).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19243012; DOI=10.1002/iub.153;
RA Hamid A., Kiran M., Rana S., Kaur J.;
RT "Low folate transport across intestinal basolateral surface is associated
RT with down-regulation of reduced folate carrier in in vivo model of folate
RT malabsorption.";
RL IUBMB Life 61:236-243(2009).
CC -!- FUNCTION: Antiporter that mediates the import of reduced folates
CC (PubMed:11600421, PubMed:19243012). Mechanistically, acts as a
CC secondary active transporter, which exports intracellular organic
CC anions down their concentration gradients to facilitate the uptake of
CC its substrates (By similarity). Has high affinity for N5-
CC methyltetrahydrofolate, the predominant circulating form of folate (By
CC similarity). Also able to mediate the import of antifolate drug
CC methotrexate (PubMed:10827155, PubMed:11600421). 5-amino-4-
CC imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR
CC monophosphate, can serve as an organic anion for antiporter activity
CC (By similarity). {ECO:0000250|UniProtKB:P41438,
CC ECO:0000250|UniProtKB:P41440, ECO:0000269|PubMed:10827155,
CC ECO:0000269|PubMed:11600421, ECO:0000269|PubMed:19243012}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate(out) + 5-amino-1-(5-
CC phospho-beta-D-ribosyl)imidazole-4-carboxamide(in) = (6S)-5-methyl-
CC 5,6,7,8-tetrahydrofolate(in) + 5-amino-1-(5-phospho-beta-D-
CC ribosyl)imidazole-4-carboxamide(out); Xref=Rhea:RHEA:60460,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:58475;
CC Evidence={ECO:0000269|PubMed:19243012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60461;
CC Evidence={ECO:0000269|PubMed:19243012};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.42 uM for folate {ECO:0000269|PubMed:19243012};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19243012};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P41440}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:19243012};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, heart, brain, spleen, lung and
CC skeletal muscle. {ECO:0000269|PubMed:10827155}.
CC -!- SIMILARITY: Belongs to the reduced folate carrier (RFC) transporter (TC
CC 2.A.48) family. {ECO:0000305}.
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DR EMBL; AF173642; AAD49426.1; -; mRNA.
DR EMBL; AF099009; AAF21822.1; -; mRNA.
DR EMBL; U38180; AAC61788.1; -; mRNA.
DR EMBL; BC085742; AAH85742.1; -; mRNA.
DR EMBL; CH473988; EDL97120.1; -; Genomic_DNA.
DR EMBL; AABR07044596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473988; EDL97117.1; -; Genomic_DNA.
DR EMBL; CH473988; EDL97118.1; -; Genomic_DNA.
DR EMBL; CH473988; EDL97119.1; -; Genomic_DNA.
DR RefSeq; NP_001030309.1; NM_001035232.1.
DR RefSeq; NP_058995.2; NM_017299.2.
DR RefSeq; XP_006256357.1; XM_006256295.3.
DR RefSeq; XP_006256358.1; XM_006256296.3.
DR RefSeq; XP_006256359.1; XM_006256297.3.
DR RefSeq; XP_006256360.1; XM_006256298.2.
DR AlphaFoldDB; Q62866; -.
DR STRING; 10116.ENSRNOP00000041562; -.
DR GlyGen; Q62866; 1 site.
DR PaxDb; Q62866; -.
DR Ensembl; ENSRNOT00000065236; ENSRNOP00000060579; ENSRNOG00000001232.
DR GeneID; 29723; -.
DR KEGG; rno:29723; -.
DR UCSC; RGD:3695; rat.
DR CTD; 6573; -.
DR RGD; 3695; Slc19a1.
DR eggNOG; KOG3810; Eukaryota.
DR GeneTree; ENSGT00950000183022; -.
DR HOGENOM; CLU_036909_2_0_1; -.
DR InParanoid; Q62866; -.
DR OMA; YVYFGYF; -.
DR OrthoDB; 795242at2759; -.
DR PhylomeDB; Q62866; -.
DR Reactome; R-RNO-196757; Metabolism of folate and pterines.
DR PRO; PR:Q62866; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Proteomes; UP000234681; Chromosome 20.
DR Bgee; ENSRNOG00000001232; Expressed in adult mammalian kidney and 18 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; ISO:RGD.
DR GO; GO:0140360; F:cyclic-GMP-AMP transmembrane transporter activity; ISO:RGD.
DR GO; GO:0008518; F:folate:anion antiporter activity; IDA:RGD.
DR GO; GO:0005542; F:folic acid binding; IDA:RGD.
DR GO; GO:0008517; F:folic acid transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015350; F:methotrexate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:1904447; P:folate import across plasma membrane; ISO:RGD.
DR GO; GO:0098838; P:folate transmembrane transport; ISO:RGD.
DR GO; GO:0015884; P:folic acid transport; IDA:RGD.
DR GO; GO:0051958; P:methotrexate transport; IDA:UniProtKB.
DR GO; GO:0015711; P:organic anion transport; IMP:ARUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; IMP:ARUK-UCL.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR002666; Folate_carrier.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR028339; SLC19A1.
DR PANTHER; PTHR10686; PTHR10686; 1.
DR PANTHER; PTHR10686:SF12; PTHR10686:SF12; 1.
DR Pfam; PF01770; Folate_carrier; 1.
DR PIRSF; PIRSF028739; Folate_carrier; 1.
DR PIRSF; PIRSF500793; Folate_transporter_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00806; rfc; 1.
PE 1: Evidence at protein level;
KW Acetylation; Antiport; Cell membrane; Folate-binding; Glycoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..512
FT /note="Reduced folate transporter"
FT /id="PRO_0000178662"
FT TOPO_DOM 1..27
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 28..48
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..64
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 65..85
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 92..112
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..121
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 122..142
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 156..176
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..180
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 181..201
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 272..292
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..304
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 305..325
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 330..350
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..354
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 355..375
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 391..411
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..426
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 427..447
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 448..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT REGION 400..412
FT /note="Required for substrate-binding"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT REGION 479..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..512
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 8
FT /note="A -> G (in Ref. 2; AAC61788)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 512 AA; 58108 MW; 70FAC54F30337B44 CRC64;
MVPTGQVAEK QACEEPRQDR ELKSWRWLVF YLCFFGFMAQ LRPGESFITP YLLERNFTKE
QVTNEIIPML PYSHLAVLVP IFLLTDYLRY KPVLVLQCLS FVCVWLLLLL GTSVVHMQLM
EVFYSITMAA RIAYSSYIFS LVQPSRYQRM ASYSRAAVLL GVFISSVLGQ VLVTLGGIST
YMLNCISLGF ILFSLSLSLF LKRPKRSLFF NRSALVQGAL PCELDQMHPG PGRPEPRKLE
RMLGTCRDSF LVRMLSELVK NVRQPQLRLW CLWWVFNSAG YYLITYYVHV LWKITDSRLN
YNGAVDAAST LLSAITAFTA GFVNIRWALW SKLVIASVIA IQAGLVFCMF QIPDIWVCYV
TFVLFRGAYQ FLVPIATFQI ASSLSKELCA LVFGINTFLA TALKTSITLV VSDKRGLGLQ
VHQQFRIYFM YFLTLSIICL AWAGLDGLRY YRRGRHQPLA QAQALSPLED SVQAISLQDG
DLRRPQPSAP QLLPEDGSVE DGRADLRVEA KA
