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Protein

Multidrug and toxin extrusion protein 1

Gene

Slc47a1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Solute transporter for tetraethylammonium (TEA), cimetidine, metformin, guanidine, N-methylnicotinamide (NMN) and also the zwitterionic cephalosporin cephalexin. Not a transporter for 1-methyl-4-phenylpyridinium (MPP), procainamide, creatinine, guanidine, p-aminohippurate (PAH) and the anionic cephalosporin cefalozin. MPP-transport activity has been observed in PubMed:16928787 and PubMed:17047166 and may contradict results observed in PubMed:16850272. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Responsible for the secretion of cationic drugs across the brush border membranes.4 Publications

Kineticsi

  1. KM=0.260 mM for TEA5 Publications
  2. KM=0.003 mM for cimetidine5 Publications

    pH dependencei

    Optimum pH is 7.5-8.4. Active from pH 6 to 8.5.5 Publications

    GO - Molecular functioni

    • drug transmembrane transporter activity Source: RGD
    • monovalent cation:proton antiporter activity Source: RGD

    GO - Biological processi

    • drug transmembrane transport Source: RGD
    • drug transport Source: RGD
    • hydrogen ion transmembrane transport Source: GOC
    • organic cation transport Source: RGD
    Complete GO annotation...

    Keywords - Biological processi

    Transport

    Enzyme and pathway databases

    ReactomeiR-RNO-425366. Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds.

    Protein family/group databases

    TCDBi2.A.66.1.15. the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Multidrug and toxin extrusion protein 1
    Short name:
    MATE-1
    Short name:
    rMATE-1
    Alternative name(s):
    Solute carrier family 47 member 1
    Gene namesi
    Name:Slc47a1
    Synonyms:Mate1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 10

    Organism-specific databases

    RGDi1311123. Slc47a1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei37 – 5721HelicalSequence analysisAdd
    BLAST
    Transmembranei72 – 9221HelicalSequence analysisAdd
    BLAST
    Transmembranei120 – 14021HelicalSequence analysisAdd
    BLAST
    Transmembranei152 – 17221HelicalSequence analysisAdd
    BLAST
    Transmembranei176 – 19621HelicalSequence analysisAdd
    BLAST
    Transmembranei216 – 23621HelicalSequence analysisAdd
    BLAST
    Transmembranei257 – 27620HelicalSequence analysisAdd
    BLAST
    Transmembranei295 – 31521HelicalSequence analysisAdd
    BLAST
    Transmembranei336 – 35621HelicalSequence analysisAdd
    BLAST
    Transmembranei370 – 39021HelicalSequence analysisAdd
    BLAST
    Transmembranei409 – 42921HelicalSequence analysisAdd
    BLAST
    Transmembranei437 – 45721HelicalSequence analysisAdd
    BLAST
    Transmembranei543 – 56321HelicalSequence analysisAdd
    BLAST

    GO - Cellular componenti

    • integral component of membrane Source: UniProtKB-KW
    • membrane-bounded vesicle Source: RGD
    • plasma membrane Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi62 – 621C → G, F, L or M: Reduction of in TEA uptake. 1 Publication
    Mutagenesisi64 – 641H → Q: No change in TEA uptake. 1 Publication
    Mutagenesisi95 – 951C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi110 – 1101H → Q: No change in TEA uptake. 1 Publication
    Mutagenesisi125 – 1251C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi126 – 1261C → G, F, L or M: Reduction of TEA uptake. 1 Publication
    Mutagenesisi129 – 1291C → G: Modest reduction of TEA uptake. 1 Publication
    Mutagenesisi209 – 2091H → Q: No change in TEA uptake. 1 Publication
    Mutagenesisi240 – 2401H → Q: No change in TEA uptake. 1 Publication
    Mutagenesisi251 – 2511C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi270 – 2701C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi356 – 3561C → G: Modest reduction of TEA uptake. 1 Publication
    Mutagenesisi385 – 3851H → Q, F, L, M, P, S or W: Important reduction of TEA uptake. 1 Publication
    Mutagenesisi392 – 3921C → G: Modest reduction of TEA uptake. 1 Publication
    Mutagenesisi444 – 4441C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi451 – 4511C → G: Modest reduction of TEA uptake. 1 Publication
    Mutagenesisi465 – 4651C → G: No change in TEA uptake. 1 Publication
    Mutagenesisi471 – 4711H → Q: No change in TEA uptake. 1 Publication
    Mutagenesisi490 – 4901H → Q: No change in TEA uptake. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 566566Multidrug and toxin extrusion protein 1PRO_0000312849Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ5I0E9.
    PRIDEiQ5I0E9.

    Expressioni

    Tissue specificityi

    Highly expressed in kidney and placenta, moderately in stomach, colon, lung, spleen, skeletal muscle and prostate, and slightly in spleen. In the kidney, found in medulla and cortex, especially in the proximal convoluted and straight tubules. No expression was observed in heart, brain, small intestine and liver.3 Publications

    Interactioni

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000054704.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1347. Eukaryota.
    COG0534. LUCA.
    GeneTreeiENSGT00390000015713.
    HOGENOMiHOG000060313.
    HOVERGENiHBG056043.
    InParanoidiQ5I0E9.
    KOiK03327.
    OMAiNTIGYYV.
    OrthoDBiEOG7RRF71.
    PhylomeDBiQ5I0E9.
    TreeFamiTF324441.

    Family and domain databases

    InterProiIPR002528. MATE_fam.
    [Graphical view]
    PfamiPF01554. MatE. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR00797. matE. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q5I0E9-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEVLEEPAPG PGGADAAERR GLRRLLLSGF QEELRALLVL AGPAFLAQLM
    60 70 80 90 100
    MFLISFISSV FCGHLGKLEL DAVTLAIAVI NVTGISVGHG LSSACDTLIS
    110 120 130 140 150
    QTYGSQNLKH VGVILQRGTL ILLLCCFPCW ALFINTEQIL LLFRQDPDVS
    160 170 180 190 200
    RLTQTYVMVF IPALPAAFLY TLQVKYLLNQ GIVLPQVITG IAANLVNALA
    210 220 230 240 250
    NYLFLHQLHL GVMGSALANT ISQFALAIFL FLYILWRKLH HATWGGWSWE
    260 270 280 290 300
    CLQDWASFLQ LAIPSMLMLC IEWWAYEVGS FLSGILGMVE LGAQSITYEL
    310 320 330 340 350
    AIIVYMIPAG FSVAANVRVG NALGAGNIDQ AKKSSAISLI VTELFAVTFC
    360 370 380 390 400
    VLLLGCKDLV GYIFTTDWDI VALVAQVVPI YAVSHLFEAL ACTCGGVLRG
    410 420 430 440 450
    TGNQKVGAIV NAIGYYVIGL PIGISLMFVA KLGVIGLWSG IIICSVCQTS
    460 470 480 490 500
    CFLVFIARLN WKLACQQAQV HANLKVNVAL NSAVSQEPAH PVGPESHGEI
    510 520 530 540 550
    MMTDLEKKDE IQLDQQMNQQ QALPVHPKDS NKLSGKQLAL RRGLLFLGVV
    560
    LVLVGGILVR VYIRTE
    Length:566
    Mass (Da):61,440
    Last modified:February 15, 2005 - v1
    Checksum:i67C9486E9F606A21
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti529 – 5291D → Y in BAF02627 (PubMed:16928787).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB248823 mRNA. Translation: BAF02626.1.
    AB248824 mRNA. Translation: BAF02627.1.
    BC088413 mRNA. Translation: AAH88413.1.
    RefSeqiNP_001014140.1. NM_001014118.2.
    UniGeneiRn.17240.

    Genome annotation databases

    EnsembliENSRNOT00000086579; ENSRNOP00000074897; ENSRNOG00000057404.
    GeneIDi360539.
    KEGGirno:360539.
    UCSCiRGD:1311123. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB248823 mRNA. Translation: BAF02626.1.
    AB248824 mRNA. Translation: BAF02627.1.
    BC088413 mRNA. Translation: AAH88413.1.
    RefSeqiNP_001014140.1. NM_001014118.2.
    UniGeneiRn.17240.

    3D structure databases

    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000054704.

    Protein family/group databases

    TCDBi2.A.66.1.15. the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.

    Proteomic databases

    PaxDbiQ5I0E9.
    PRIDEiQ5I0E9.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000086579; ENSRNOP00000074897; ENSRNOG00000057404.
    GeneIDi360539.
    KEGGirno:360539.
    UCSCiRGD:1311123. rat.

    Organism-specific databases

    CTDi55244.
    RGDi1311123. Slc47a1.

    Phylogenomic databases

    eggNOGiKOG1347. Eukaryota.
    COG0534. LUCA.
    GeneTreeiENSGT00390000015713.
    HOGENOMiHOG000060313.
    HOVERGENiHBG056043.
    InParanoidiQ5I0E9.
    KOiK03327.
    OMAiNTIGYYV.
    OrthoDBiEOG7RRF71.
    PhylomeDBiQ5I0E9.
    TreeFamiTF324441.

    Enzyme and pathway databases

    ReactomeiR-RNO-425366. Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds.

    Miscellaneous databases

    PROiQ5I0E9.

    Family and domain databases

    InterProiIPR002528. MATE_fam.
    [Graphical view]
    PfamiPF01554. MatE. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR00797. matE. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney."
      Ohta K.Y., Inoue K., Hayashi Y., Yuasa H.
      Drug Metab. Dispos. 34:1868-1874(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
      Tissue: Kidney.
    2. "Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1."
      Terada T., Masuda S., Asaka J., Tsuda M., Katsura T., Inui K.
      Pharm. Res. 23:1696-1701(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, FUNCTION.
      Tissue: Kidney.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.
    4. "Oppositely directed H+ gradient functions as a driving force of rat H+/organic cation antiporter MATE1."
      Tsuda M., Terada T., Asaka J., Ueba M., Katsura T., Inui K.
      Am. J. Physiol. 292:F593-F598(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity."
      Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K.
      Biochem. Pharmacol. 74:477-487(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure rats."
      Nishihara K., Masuda S., Ji L., Katsura T., Inui K.
      Biochem. Pharmacol. 73:1482-1490(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    7. "Identification of essential histidine and cysteine residues of the H+/organic cation antiporter multidrug and toxin extrusion (MATE)."
      Asaka J., Terada T., Tsuda M., Katsura T., Inui K.
      Mol. Pharmacol. 71:1487-1493(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF CYS-62; HIS-64; CYS-95; HIS-110; CYS-125; CYS-126; CYS-129; HIS-209; HIS-240; CYS-251; CYS-270; CYS-356; HIS-385; CYS-392; CYS-444; CYS-451; CYS-465; HIS-471 AND HIS-490, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
    8. "Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications."
      Koepsell H., Lips K., Volk C.
      Pharm. Res. 24:1227-1251(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES.

    Entry informationi

    Entry nameiS47A1_RAT
    AccessioniPrimary (citable) accession number: Q5I0E9
    Secondary accession number(s): Q0KKE7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: February 15, 2005
    Last modified: June 8, 2016
    This is version 89 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.