S19A1_CRIGR
ID S19A1_CRIGR Reviewed; 518 AA.
AC P42557; G3H8Y7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Reduced folate transporter {ECO:0000305};
DE AltName: Full=Methotrexate uptake protein {ECO:0000303|PubMed:8119923};
DE AltName: Full=Plasma membrane folate antiporter SLC19A1 {ECO:0000305};
DE AltName: Full=Reduced folate carrier 1 {ECO:0000250|UniProtKB:P41440};
DE Short=RFC-1 {ECO:0000250|UniProtKB:P41440};
DE Short=RFC1 {ECO:0000250|UniProtKB:P41440};
DE AltName: Full=Solute carrier family 19 member 1 {ECO:0000250|UniProtKB:P41440};
GN Name=SLC19A1 {ECO:0000250|UniProtKB:P41440};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=8119923; DOI=10.1016/s0021-9258(17)37534-8;
RA Williams F.M.R., Murray R.C., Underhill T.M., Flintoff W.F.;
RT "Isolation of a hamster cDNA clone coding for a function involved in
RT methotrexate uptake.";
RL J. Biol. Chem. 269:5810-5816(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
CC -!- FUNCTION: Antiporter that mediates the import of reduced folates (By
CC similarity). Mechanistically, acts as a secondary active transporter,
CC which exports intracellular organic anions down their concentration
CC gradients to facilitate the uptake of its substrates (By similarity).
CC Has high affinity for N5-methyltetrahydrofolate, the predominant
CC circulating form of folate. Also able to mediate the import of
CC antifolate drug methotrexate (By similarity). 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}.
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:0000250|UniProtKB:P41440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60461;
CC Evidence={ECO:0000250|UniProtKB:P41440};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P41440};
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
CC {ECO:0000250|UniProtKB:P41440}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the reduced folate carrier (RFC) transporter (TC
CC 2.A.48) family. {ECO:0000305}.
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DR EMBL; U03031; AAC52138.1; -; mRNA.
DR EMBL; JH000220; EGV98038.1; -; Genomic_DNA.
DR PIR; A53207; A53207.
DR RefSeq; NP_001233760.1; NM_001246831.1.
DR RefSeq; XP_007639501.1; XM_007641311.2.
DR RefSeq; XP_007639502.1; XM_007641312.2.
DR RefSeq; XP_007639503.1; XM_007641313.2.
DR RefSeq; XP_007639504.1; XM_007641314.2.
DR RefSeq; XP_007639506.1; XM_007641316.2.
DR AlphaFoldDB; P42557; -.
DR STRING; 10029.NP_001233760.1; -.
DR Ensembl; ENSCGRT00001020802; ENSCGRP00001016558; ENSCGRG00001016846.
DR GeneID; 100689407; -.
DR KEGG; cge:100689407; -.
DR CTD; 6573; -.
DR eggNOG; KOG3810; Eukaryota.
DR GeneTree; ENSGT00950000183022; -.
DR OMA; YVYFGYF; -.
DR OrthoDB; 795242at2759; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IEA:Ensembl.
DR GO; GO:0140360; F:cyclic-GMP-AMP transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0008518; F:folate:anion antiporter activity; IEA:Ensembl.
DR GO; GO:0005542; F:folic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0015350; F:methotrexate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; IEA:Ensembl.
DR GO; GO:1904447; P:folate import across plasma membrane; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Acetylation; Antiport; Cell membrane; Folate-binding; Glycoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..518
FT /note="Reduced folate transporter"
FT /id="PRO_0000178659"
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..90
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 91..111
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..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..179
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 180..202
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 274..294
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..303
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 304..324
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 331..351
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 352..361
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 362..382
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..397
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 398..418
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 419..431
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT TRANSMEM 432..452
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT REGION 407..419
FT /note="Required for substrate-binding"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT REGION 480..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P41440"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41438"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 268..269
FT /note="QL -> HV (in Ref. 1; AAC52138)"
FT CONFLICT 487
FT /note="G -> R (in Ref. 1; AAC52138)"
SQ SEQUENCE 518 AA; 58517 MW; 7DC5A24713402B8E CRC64;
MVPTGQVAEK QACEEPRQDR ELKSWRCLVF YLCFFGFMAQ LRPGESFITP YLLQQNFTIE
QVTNEIIPVL PYSHLAVLVP IFLLTDYLRY KPILILQCLS FMCVWLLLLL GTSVVHMQLM
EVFYSVTMAA RIAYSSYIFS LVRPSRYQRM ASYSRAAVLL GVFTSSVLGQ VLWPLEQKSQ
NSNMLNYISL GFIIFSLGLS LFLKRPKHSL FFNRSALVHK ALPCELDQMH PGPGRPEPGK
LERVLGSCRN SFLVCMLSEL VGNLRQPQLR LWCLWWVFNS AGYYLIVYYV HVLWSIDKNL
NYNGAVDAAS TLLSAITSFS AGFVKIRWAL WSKLVIASVI AIQAGLVFCM YMVHYVTWVH
KIWVLYMTYV LFRGAYQFLV PIATFQIASS LSKELCALVF GINTFLATAL KTAITLVVSD
KRGLGLKVEK QFCIYSVYFM VLSVICFVGA VLDGVRYCRR GRHQPLPLPQ ELSPLENSVQ
VPSMQDGGLG GLQPSAPQLL PEDGVEDSEA SLRAEAKA
