GENTAUR Molecular Products.

 S47A1_HUMAN             Reviewed;         570 AA.
 Q96FL8; Q53HF5; Q6PD77; Q86VL4; Q9NVA3;
 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
 01-DEC-2001, sequence version 1.
 12-SEP-2018, entry version 130.
 RecName: Full=Multidrug and toxin extrusion protein 1;
          Short=MATE-1;
          Short=hMATE-1;
 AltName: Full=Solute carrier family 47 member 1;
 Name=SLC47A1; Synonyms=MATE1;
 Homo sapiens (Human).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
 Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
 Catarrhini; Hominidae; Homo.
 NCBI_TaxID=9606;
 [1]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
 PubMed=14702039; DOI=10.1038/ng1285;
 Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
 Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
 Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
 Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
 Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
 Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
 Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
 Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
 Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
 Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
 Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
 Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
 Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
 Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
 Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
 Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
 Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
 Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
 Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
 Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
 Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
 Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
 Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
 Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
 Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
 Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
 Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
 Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
 "Complete sequencing and characterization of 21,243 full-length human
 cDNAs.";
 Nat. Genet. 36:40-45(2004).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
 TISSUE=Cerebellum;
 Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
 Tanaka A., Yokoyama S.;
 Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
 [3]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
 Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
 Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
 Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
 Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
 Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
 Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
 Venter J.C.;
 Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
 [4]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
 TISSUE=Colon, and Eye;
 PubMed=15489334; DOI=10.1101/gr.2596504;
 The MGC Project Team;
 "The status, quality, and expansion of the NIH full-length cDNA
 project: the Mammalian Gene Collection (MGC).";
 Genome Res. 14:2121-2127(2004).
 [5]
 FUNCTION, MUTAGENESIS OF GLU-273, TISSUE SPECIFICITY, SUBCELLULAR
 LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
 PubMed=16330770; DOI=10.1073/pnas.0506483102;
 Otsuka M., Matsumoto T., Morimoto R., Arioka S., Omote H.,
 Moriyama Y.;
 "A human transporter protein that mediates the final excretion step
 for toxic organic cations.";
 Proc. Natl. Acad. Sci. U.S.A. 102:17923-17928(2005).
 [6]
 SUBCELLULAR LOCATION.
 PubMed=16641166; DOI=10.1152/ajpcell.00090.2006;
 Hiasa M., Matsumoto T., Komatsu T., Moriyama Y.;
 "Wide variety of locations for rodent MATE1, a transporter protein
 that mediates the final excretion step for toxic organic cations.";
 Am. J. Physiol. 291:C678-C686(2006).
 [7]
 FUNCTION.
 PubMed=16996621; DOI=10.1016/j.tips.2006.09.001;
 Omote H., Hiasa M., Matsumoto T., Otsuka M., Moriyama Y.;
 "The MATE proteins as fundamental transporters of metabolic and
 xenobiotic organic cations.";
 Trends Pharmacol. Sci. 27:587-593(2006).
 [8]
 FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
 PubMed=17509534; DOI=10.1016/j.bcp.2007.04.010;
 Tanihara Y., Masuda S., Sato T., Katsura T., Ogawa O., Inui K.;
 "Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin
 extrusions/H(+)-organic cation antiporters.";
 Biochem. Pharmacol. 74:359-371(2007).
 [9]
 FUNCTION.
 PubMed=17582384; DOI=10.1016/j.bcp.2007.03.004;
 Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K.;
 "Differential contribution of organic cation transporters, OCT2 and
 MATE1, in platinum agent-induced nephrotoxicity.";
 Biochem. Pharmacol. 74:477-487(2007).
 [10]
 FUNCTION.
 PubMed=17495125; DOI=10.1124/jpet.107.123554;
 Chen Y., Zhang S., Sorani M., Giacomini K.M.;
 "Transport of paraquat by human organic cation transporters and
 multidrug and toxic compound extrusion family.";
 J. Pharmacol. Exp. Ther. 322:695-700(2007).
 [11]
 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
 MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=22814378; DOI=10.1073/pnas.1210303109;
 Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
 Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
 Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
 Aldabe R.;
 "N-terminal acetylome analyses and functional insights of the N-
 terminal acetyltransferase NatB.";
 Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
 -!- FUNCTION: Solute transporter for tetraethylammonium (TEA), 1-
     methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide
     (NMN), metformin, creatinine, guanidine, procainamide, topotecan,
     estrone sulfate, acyclovir, ganciclovir and also the zwitterionic
     cephalosporin, cephalexin and cephradin. Seems to also play a role
     in the uptake of oxaliplatin (a new platinum anticancer agent).
     Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium);
     a widely used herbicid. Responsible for the secretion of cationic
     drugs across the brush border membranes.
     {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:16996621,
     ECO:0000269|PubMed:17495125, ECO:0000269|PubMed:17509534,
     ECO:0000269|PubMed:17582384}.
 -!- BIOPHYSICOCHEMICAL PROPERTIES:
     Kinetic parameters:
       KM=0.38 mM for TEA {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=0.10 mM for MPP {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=0.17 mM for cimetidine {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=0.78 mM for metformin {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=2.1 mM for guanidine {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=1.23 mM for procainamide {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=0.07 mM for topotecan {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=0.47 mM for estrone sulfate {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=2.64 mM for acyclovir {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       KM=5.12 mM for ganciclovir {ECO:0000269|PubMed:16330770,
       ECO:0000269|PubMed:17509534};
       Vmax=1.185 nmol/min/mg enzyme toward TEA
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.735 nmol/min/mg enzyme toward MPP
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.135 nmol/min/mg enzyme toward cimetidine
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=2.23 nmol/min/mg enzyme toward metformin
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.89 nmol/min/mg enzyme toward guanidine
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=3.78 nmol/min/mg enzyme toward procainamide
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.21 nmol/min/mg enzyme toward topotecan
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.265 nmol/min/mg enzyme toward estrone sulfate
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=0.62 nmol/min/mg enzyme toward acyclovir
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
       Vmax=1.08 nmol/min/mg enzyme toward ganciclovir
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
     pH dependence:
       Optimum pH is 8.5. Active from pH 6 to 8.5.
       {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17509534};
 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16330770,
     ECO:0000269|PubMed:16641166}; Multi-pass membrane protein
     {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:16641166}.
     Note=Predominantly localized at the plasma membrane but also found
     in intracellular organelles.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=3;
     Name=1;
       IsoId=Q96FL8-1; Sequence=Displayed;
     Name=2;
       IsoId=Q96FL8-2; Sequence=VSP_029903, VSP_029904;
       Note=No experimental confirmation available.;
     Name=3;
       IsoId=Q96FL8-3; Sequence=VSP_029905;
       Note=No experimental confirmation available.;
 -!- TISSUE SPECIFICITY: Expressed in adrenal gland, and to a lower
     extent in liver, skeletal muscle and kidney (especially found in
     luminal membranes of the urinary tubules, bile caniculi and brush
     border membranes). {ECO:0000269|PubMed:16330770,
     ECO:0000269|PubMed:17509534}.
 -!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE)
     (TC 2.A.66.1) family. {ECO:0000305}.
 -!- SEQUENCE CAUTION:
     Sequence=AAH50592.1; Type=Erroneous initiation; Evidence={ECO:0000305};
 -----------------------------------------------------------------------
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 -----------------------------------------------------------------------
 EMBL; AK001709; BAA91852.1; -; mRNA.
 EMBL; AK222625; BAD96345.1; -; mRNA.
 EMBL; CH471212; EAW50893.1; -; Genomic_DNA.
 EMBL; CH471212; EAW50894.1; -; Genomic_DNA.
 EMBL; BC010661; AAH10661.1; -; mRNA.
 EMBL; BC050592; AAH50592.1; ALT_INIT; mRNA.
 EMBL; BC058882; AAH58882.1; -; mRNA.
 CCDS; CCDS11209.1; -. [Q96FL8-1]
 RefSeq; NP_060712.2; NM_018242.2. [Q96FL8-1]
 UniGene; Hs.232054; -.
 ProteinModelPortal; Q96FL8; -.
 BioGrid; 120535; 42.
 IntAct; Q96FL8; 1.
 STRING; 9606.ENSP00000270570; -.
 BindingDB; Q96FL8; -.
 ChEMBL; CHEMBL1743126; -.
 DrugBank; DB00787; Aciclovir.
 DrugBank; DB01237; Bromodiphenhydramine.
 DrugBank; DB00567; Cephalexin.
 DrugBank; DB00501; Cimetidine.
 DrugBank; DB00331; Metformin.
 DrugBank; DB00877; Sirolimus.
 GuidetoPHARMACOLOGY; 1216; -.
 TCDB; 2.A.66.1.14; the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.
 iPTMnet; Q96FL8; -.
 PhosphoSitePlus; Q96FL8; -.
 BioMuta; SLC47A1; -.
 DMDM; 74731723; -.
 MaxQB; Q96FL8; -.
 PaxDb; Q96FL8; -.
 PeptideAtlas; Q96FL8; -.
 PRIDE; Q96FL8; -.
 ProteomicsDB; 76538; -.
 ProteomicsDB; 76539; -. [Q96FL8-2]
 ProteomicsDB; 76540; -. [Q96FL8-3]
 Ensembl; ENST00000270570; ENSP00000270570; ENSG00000142494. [Q96FL8-1]
 Ensembl; ENST00000395585; ENSP00000378951; ENSG00000142494. [Q96FL8-3]
 GeneID; 55244; -.
 KEGG; hsa:55244; -.
 UCSC; uc002gvx.4; human. [Q96FL8-1]
 CTD; 55244; -.
 DisGeNET; 55244; -.
 EuPathDB; HostDB:ENSG00000142494.13; -.
 GeneCards; SLC47A1; -.
 H-InvDB; HIX0013619; -.
 HGNC; HGNC:25588; SLC47A1.
 HPA; HPA021987; -.
 MIM; 609832; gene.
 neXtProt; NX_Q96FL8; -.
 OpenTargets; ENSG00000142494; -.
 PharmGKB; PA162403808; -.
 eggNOG; KOG1347; Eukaryota.
 eggNOG; COG0534; LUCA.
 GeneTree; ENSGT00390000015713; -.
 HOGENOM; HOG000060313; -.
 HOVERGEN; HBG056043; -.
 InParanoid; Q96FL8; -.
 KO; K03327; -.
 OMA; LCMEWWA; -.
 OrthoDB; EOG091G06X2; -.
 PhylomeDB; Q96FL8; -.
 TreeFam; TF324441; -.
 Reactome; R-HSA-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
 ChiTaRS; SLC47A1; human.
 GeneWiki; SLC47A1; -.
 GenomeRNAi; 55244; -.
 PRO; PR:Q96FL8; -.
 Proteomes; UP000005640; Chromosome 17.
 Bgee; ENSG00000142494; Expressed in 175 organ(s), highest expression level in adrenal gland.
 CleanEx; HS_SLC47A1; -.
 ExpressionAtlas; Q96FL8; baseline and differential.
 Genevisible; Q96FL8; HS.
 GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
 GO; GO:0005886; C:plasma membrane; TAS:Reactome.
 GO; GO:0031982; C:vesicle; IBA:GO_Central.
 GO; GO:0015238; F:drug transmembrane transporter activity; IBA:GO_Central.
 GO; GO:0015307; F:drug:proton antiporter activity; TAS:Reactome.
 GO; GO:0005451; F:monovalent cation:proton antiporter activity; IBA:GO_Central.
 GO; GO:0006855; P:drug transmembrane transport; IBA:GO_Central.
 GO; GO:0015695; P:organic cation transport; IBA:GO_Central.
 GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
 InterPro; IPR002528; MATE_fam.
 Pfam; PF01554; MatE; 2.
 TIGRFAMs; TIGR00797; matE; 1.
 1: Evidence at protein level;
 Acetylation; Alternative splicing; Cell membrane; Complete proteome;
 Membrane; Polymorphism; Reference proteome; Transmembrane;
 Transmembrane helix; Transport.
 CHAIN         1    570       Multidrug and toxin extrusion protein 1.
                              /FTId=PRO_0000312845.
 TOPO_DOM      1     37       Cytoplasmic. {ECO:0000255}.
 TRANSMEM     38     58       Helical. {ECO:0000255}.
 TOPO_DOM     59     72       Extracellular. {ECO:0000255}.
 TRANSMEM     73     93       Helical. {ECO:0000255}.
 TOPO_DOM     94    123       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    124    144       Helical. {ECO:0000255}.
 TOPO_DOM    145    152       Extracellular. {ECO:0000255}.
 TRANSMEM    153    173       Helical. {ECO:0000255}.
 TOPO_DOM    174    176       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    177    197       Helical. {ECO:0000255}.
 TOPO_DOM    198    216       Extracellular. {ECO:0000255}.
 TRANSMEM    217    237       Helical. {ECO:0000255}.
 TOPO_DOM    238    256       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    257    276       Helical. {ECO:0000255}.
 TOPO_DOM    277    295       Extracellular. {ECO:0000255}.
 TRANSMEM    296    316       Helical. {ECO:0000255}.
 TOPO_DOM    317    336       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    337    357       Helical. {ECO:0000255}.
 TOPO_DOM    358    370       Extracellular. {ECO:0000255}.
 TRANSMEM    371    391       Helical. {ECO:0000255}.
 TOPO_DOM    392    408       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    409    429       Helical. {ECO:0000255}.
 TOPO_DOM    430    437       Extracellular. {ECO:0000255}.
 TRANSMEM    438    458       Helical. {ECO:0000255}.
 TOPO_DOM    459    546       Cytoplasmic. {ECO:0000255}.
 TRANSMEM    547    567       Helical. {ECO:0000255}.
 TOPO_DOM    568    570       Extracellular. {ECO:0000255}.
 MOD_RES       1      1       N-acetylmethionine.
                              {ECO:0000244|PubMed:22814378}.
 VAR_SEQ     286    290       ILGMV -> LYEDG (in isoform 2).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_029903.
 VAR_SEQ     291    570       Missing (in isoform 2).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_029904.
 VAR_SEQ     559    570       VGILVRFYVRIQ -> AGVRWCDHSSLQPRTLGLQAILLCQ
                              PPE (in isoform 3).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_029905.
 VARIANT     338    338       V -> I (in dbSNP:rs35790011).
                              /FTId=VAR_037587.
 MUTAGEN     273    273       E->Q: No change in subcellular location
                              and abolition of MATE1-dependent TEA
                              transport activity.
                              {ECO:0000269|PubMed:16330770}.
 CONFLICT     50     50       L -> R (in Ref. 2; BAD96345).
                              {ECO:0000305}.
 CONFLICT    309    309       P -> L (in Ref. 1; BAA91852).
                              {ECO:0000305}.
 CONFLICT    448    448       F -> L (in Ref. 2; BAD96345).
                              {ECO:0000305}.
 CONFLICT    507    507       N -> D (in Ref. 2; BAD96345).
                              {ECO:0000305}.
 SEQUENCE   570 AA;  61922 MW;  CA940CBC2F6F5CC4 CRC64;
 MEAPEEPAPV RGGPEATLEV RGSRCLRLSA FREELRALLV LAGPAFLVQL MVFLISFISS
 VFCGHLGKLE LDAVTLAIAV INVTGVSVGF GLSSACDTLI SQTYGSQNLK HVGVILQRSA
 LVLLLCCFPC WALFLNTQHI LLLFRQDPDV SRLTQTYVTI FIPALPATFL YMLQVKYLLN
 QGIVLPQIVT GVAANLVNAL ANYLFLHQLH LGVIGSALAN LISQYTLALL LFLYILGKKL
 HQATWGGWSL ECLQDWASFL RLAIPSMLML CMEWWAYEVG SFLSGILGMV ELGAQSIVYE
 LAIIVYMVPA GFSVAASVRV GNALGAGDME QARKSSTVSL LITVLFAVAF SVLLLSCKDH
 VGYIFTTDRD IINLVAQVVP IYAVSHLFEA LACTSGGVLR GSGNQKVGAI VNTIGYYVVG
 LPIGIALMFA TTLGVMGLWS GIIICTVFQA VCFLGFIIQL NWKKACQQAQ VHANLKVNNV
 PRSGNSALPQ DPLHPGCPEN LEGILTNDVG KTGEPQSDQQ MRQEEPLPEH PQDGAKLSRK
 QLVLRRGLLL LGVFLILLVG ILVRFYVRIQ

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