S47A1_RAT
ID S47A1_RAT Reviewed; 566 AA.
AC Q5I0E9; Q0KKE7;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Multidrug and toxin extrusion protein 1;
DE Short=MATE-1;
DE Short=rMATE-1;
DE AltName: Full=Solute carrier family 47 member 1;
GN Name=Slc47a1; Synonyms=Mate1;
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, TISSUE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Kidney;
RX PubMed=16928787; DOI=10.1124/dmd.106.010876;
RA Ohta K.Y., Inoue K., Hayashi Y., Yuasa H.;
RT "Molecular identification and functional characterization of rat multidrug
RT and toxin extrusion type transporter 1 as an organic cation/H+ antiporter
RT in the kidney.";
RL Drug Metab. Dispos. 34:1868-1874(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=16850272; DOI=10.1007/s11095-006-9016-3;
RA Terada T., Masuda S., Asaka J., Tsuda M., Katsura T., Inui K.;
RT "Molecular cloning, functional characterization and tissue distribution of
RT rat H+/organic cation antiporter MATE1.";
RL Pharm. Res. 23:1696-1701(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17047166; DOI=10.1152/ajprenal.00312.2006;
RA Tsuda M., Terada T., Asaka J., Ueba M., Katsura T., Inui K.;
RT "Oppositely directed H+ gradient functions as a driving force of rat
RT H+/organic cation antiporter MATE1.";
RL Am. J. Physiol. 292:F593-F598(2007).
RN [5]
RP FUNCTION.
RX PubMed=17582384; DOI=10.1016/j.bcp.2007.03.004;
RA Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K.;
RT "Differential contribution of organic cation transporters, OCT2 and MATE1,
RT in platinum agent-induced nephrotoxicity.";
RL Biochem. Pharmacol. 74:477-487(2007).
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17296166; DOI=10.1016/j.bcp.2006.12.034;
RA Nishihara K., Masuda S., Ji L., Katsura T., Inui K.;
RT "Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in
RT chronic renal failure rats.";
RL Biochem. Pharmacol. 73:1482-1490(2007).
RN [7]
RP MUTAGENESIS OF CYS-62; HIS-64; CYS-95; HIS-110; CYS-125; CYS-126; CYS-129;
RP HIS-209; HIS-240; CYS-251; CYS-270; CYS-356; HIS-385; CYS-392; CYS-444;
RP CYS-451; CYS-465; HIS-471 AND HIS-490, SUBCELLULAR LOCATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17327464; DOI=10.1124/mol.106.032938;
RA Asaka J., Terada T., Tsuda M., Katsura T., Inui K.;
RT "Identification of essential histidine and cysteine residues of the
RT H+/organic cation antiporter multidrug and toxin extrusion (MATE).";
RL Mol. Pharmacol. 71:1487-1493(2007).
RN [8]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17473959; DOI=10.1007/s11095-007-9254-z;
RA Koepsell H., Lips K., Volk C.;
RT "Polyspecific organic cation transporters: structure, function,
RT physiological roles, and biopharmaceutical implications.";
RL Pharm. Res. 24:1227-1251(2007).
CC -!- FUNCTION: Solute transporter for tetraethylammonium (TEA), cimetidine,
CC metformin, guanidine, N-methylnicotinamide (NMN) and also the
CC zwitterionic cephalosporin cephalexin. Not a transporter for 1-methyl-
CC 4-phenylpyridinium (MPP), procainamide, creatinine, guanidine, p-
CC aminohippurate (PAH) and the anionic cephalosporin cefalozin. MPP-
CC transport activity has been observed in PubMed:16928787 and
CC PubMed:17047166 and may contradict results observed in PubMed:16850272.
CC Seems to also play a role in the uptake of oxaliplatin (a new platinum
CC anticancer agent). Responsible for the secretion of cationic drugs
CC across the brush border membranes. {ECO:0000269|PubMed:16850272,
CC ECO:0000269|PubMed:16928787, ECO:0000269|PubMed:17047166,
CC ECO:0000269|PubMed:17582384}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.260 mM for TEA {ECO:0000269|PubMed:16850272,
CC ECO:0000269|PubMed:16928787, ECO:0000269|PubMed:17047166,
CC ECO:0000269|PubMed:17327464, ECO:0000269|PubMed:17473959};
CC KM=0.003 mM for cimetidine {ECO:0000269|PubMed:16850272,
CC ECO:0000269|PubMed:16928787, ECO:0000269|PubMed:17047166,
CC ECO:0000269|PubMed:17327464, ECO:0000269|PubMed:17473959};
CC pH dependence:
CC Optimum pH is 7.5-8.4. Active from pH 6 to 8.5.
CC {ECO:0000269|PubMed:16850272, ECO:0000269|PubMed:16928787,
CC ECO:0000269|PubMed:17047166, ECO:0000269|PubMed:17327464,
CC ECO:0000269|PubMed:17473959};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17296166,
CC ECO:0000269|PubMed:17327464}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17296166, ECO:0000269|PubMed:17327464}.
CC Note=Predominantly localized at the plasma membrane but also found in
CC intracellular organelles.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and placenta, moderately
CC in stomach, colon, lung, spleen, skeletal muscle and prostate, and
CC slightly in spleen. In the kidney, found in medulla and cortex,
CC especially in the proximal convoluted and straight tubules. No
CC expression was observed in heart, brain, small intestine and liver.
CC {ECO:0000269|PubMed:16850272, ECO:0000269|PubMed:16928787,
CC ECO:0000269|PubMed:17296166}.
CC -!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE) (TC
CC 2.A.66.1) family. {ECO:0000305}.
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DR EMBL; AB248823; BAF02626.1; -; mRNA.
DR EMBL; AB248824; BAF02627.1; -; mRNA.
DR EMBL; BC088413; AAH88413.1; -; mRNA.
DR RefSeq; NP_001014140.1; NM_001014118.2.
DR AlphaFoldDB; Q5I0E9; -.
DR SMR; Q5I0E9; -.
DR STRING; 10116.ENSRNOP00000054704; -.
DR TCDB; 2.A.66.1.15; the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.
DR PaxDb; Q5I0E9; -.
DR PRIDE; Q5I0E9; -.
DR GeneID; 360539; -.
DR KEGG; rno:360539; -.
DR UCSC; RGD:1311123; rat.
DR CTD; 55244; -.
DR RGD; 1311123; Slc47a1.
DR VEuPathDB; HostDB:ENSRNOG00000057404; -.
DR eggNOG; KOG1347; Eukaryota.
DR HOGENOM; CLU_012893_1_3_1; -.
DR InParanoid; Q5I0E9; -.
DR OMA; TGNQKVG; -.
DR OrthoDB; 743037at2759; -.
DR PhylomeDB; Q5I0E9; -.
DR TreeFam; TF324441; -.
DR Reactome; R-RNO-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR PRO; PR:Q5I0E9; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000057404; Expressed in adult mammalian kidney and 12 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0042887; F:amide transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015297; F:antiporter activity; IEA:InterPro.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0061459; F:L-arginine transmembrane transporter activity; ISO:RGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:RGD.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:RGD.
DR GO; GO:0098655; P:cation transmembrane transport; IDA:RGD.
DR GO; GO:0006812; P:cation transport; IMP:RGD.
DR GO; GO:1902475; P:L-alpha-amino acid transmembrane transport; ISO:RGD.
DR GO; GO:0097638; P:L-arginine import across plasma membrane; ISO:RGD.
DR GO; GO:0015695; P:organic cation transport; IDA:RGD.
DR GO; GO:0055085; P:transmembrane transport; IDA:RGD.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IEA:InterPro.
DR GO; GO:0042908; P:xenobiotic transport; ISO:RGD.
DR CDD; cd13132; MATE_eukaryotic; 1.
DR InterPro; IPR045069; MATE_euk.
DR InterPro; IPR002528; MATE_fam.
DR Pfam; PF01554; MatE; 2.
DR TIGRFAMs; TIGR00797; matE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..566
FT /note="Multidrug and toxin extrusion protein 1"
FT /id="PRO_0000312849"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 437..457
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 543..563
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q96FL8"
FT MUTAGEN 62
FT /note="C->G,F,L,M: Reduction of in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 64
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 95
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 110
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 125
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 126
FT /note="C->G,F,L,M: Reduction of TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 129
FT /note="C->G: Modest reduction of TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 209
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 240
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 251
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 270
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 356
FT /note="C->G: Modest reduction of TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 385
FT /note="H->Q,F,L,M,P,S,W: Important reduction of TEA
FT uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 392
FT /note="C->G: Modest reduction of TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 444
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 451
FT /note="C->G: Modest reduction of TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 465
FT /note="C->G: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 471
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT MUTAGEN 490
FT /note="H->Q: No change in TEA uptake."
FT /evidence="ECO:0000269|PubMed:17327464"
FT CONFLICT 529
FT /note="D -> Y (in Ref. 1; BAF02627)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 566 AA; 61440 MW; 67C9486E9F606A21 CRC64;
MEVLEEPAPG PGGADAAERR GLRRLLLSGF QEELRALLVL AGPAFLAQLM MFLISFISSV
FCGHLGKLEL DAVTLAIAVI NVTGISVGHG LSSACDTLIS QTYGSQNLKH VGVILQRGTL
ILLLCCFPCW ALFINTEQIL LLFRQDPDVS RLTQTYVMVF IPALPAAFLY TLQVKYLLNQ
GIVLPQVITG IAANLVNALA NYLFLHQLHL GVMGSALANT ISQFALAIFL FLYILWRKLH
HATWGGWSWE CLQDWASFLQ LAIPSMLMLC IEWWAYEVGS FLSGILGMVE LGAQSITYEL
AIIVYMIPAG FSVAANVRVG NALGAGNIDQ AKKSSAISLI VTELFAVTFC VLLLGCKDLV
GYIFTTDWDI VALVAQVVPI YAVSHLFEAL ACTCGGVLRG TGNQKVGAIV NAIGYYVIGL
PIGISLMFVA KLGVIGLWSG IIICSVCQTS CFLVFIARLN WKLACQQAQV HANLKVNVAL
NSAVSQEPAH PVGPESHGEI MMTDLEKKDE IQLDQQMNQQ QALPVHPKDS NKLSGKQLAL
RRGLLFLGVV LVLVGGILVR VYIRTE
