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Multidrug and toxin extrusion protein 2 (MATE-2) (hMATE-2) (Kidney-specific H( )/organic cation antiporter) (Solute carrier family 47 member 2)

 S47A2_HUMAN             Reviewed;         602 AA.
Q86VL8; A0JBX9; A0P8Z7; Q63HJ9; Q8IV44; Q96NA1;
04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
01-JUN-2003, sequence version 1.
28-FEB-2018, entry version 116.
RecName: Full=Multidrug and toxin extrusion protein 2;
Short=MATE-2;
Short=hMATE-2;
AltName: Full=Kidney-specific H(+)/organic cation antiporter;
AltName: Full=Solute carrier family 47 member 2;
Name=SLC47A2; Synonyms=MATE2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 6), TISSUE SPECIFICITY,
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
TISSUE=Brain, and Kidney;
PubMed=16807400; DOI=10.1681/ASN.2006030205;
Masuda S., Terada T., Yonezawa A., Tanihara Y., Kishimoto K.,
Katsura T., Ogawa O., Inui K.;
"Identification and functional characterization of a new human kidney-
specific H+/organic cation antiporter, kidney-specific multidrug and
toxin extrusion 2.";
J. Am. Soc. Nephrol. 17:2127-2135(2006).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
TISSUE=Kidney;
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).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Small intestine;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[4]
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.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
TISSUE=Colon;
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).
[6]
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).
[7]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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).
-!- FUNCTION: Solute transporter for tetraethylammonium (TEA), 1-
methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide,
metformin, creatinine, guanidine, procainamide, topotecan, estrone
sulfate, acyclovir, and ganciclovir. Responsible for the secretion
of cationic drugs across the brush border membranes.
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:16996621,
ECO:0000269|PubMed:17509534}.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=0.76 mM for TEA {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=0.11 mM for MPP {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=0.12 mM for cimetidine {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=1.98 mM for metformin {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=4.2 mM for guanidine {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=1.58 mM for procainamide {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=0.06 mM for topotecan {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=0.85 mM for estrone sulfate {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=4.32 mM for acyclovir {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
KM=4.28 mM for ganciclovir {ECO:0000269|PubMed:16807400,
ECO:0000269|PubMed:17509534};
Vmax=0.88 nmol/min/mg enzyme toward TEA
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.575 nmol/min/mg enzyme toward MPP
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.115 nmol/min/mg enzyme toward cimetidine
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.845 nmol/min/mg enzyme toward metformin
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.58 nmol/min/mg enzyme toward guanidine
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=3.385 nmol/min/mg enzyme toward procainamide
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.13 nmol/min/mg enzyme toward topotecan
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.425 nmol/min/mg enzyme toward estrone sulfate
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.945 nmol/min/mg enzyme toward acyclovir
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
Vmax=0.805 nmol/min/mg enzyme toward ganciclovir
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
pH dependence:
Optimum pH is 9.0. Active from pH 6 to 9.
{ECO:0000269|PubMed:16807400, ECO:0000269|PubMed:17509534};
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass
membrane protein {ECO:0000305}. Note=Localized at the brush border
membranes of the proximal tubules.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=6;
Name=1;
IsoId=Q86VL8-1; Sequence=Displayed;
Name=2;
IsoId=Q86VL8-2; Sequence=VSP_029656, VSP_029658, VSP_029663,
VSP_029664;
Note=No experimental confirmation available.;
Name=3; Synonyms=MATE2-K;
IsoId=Q86VL8-3; Sequence=VSP_029658;
Note=No experimental confirmation available.;
Name=4;
IsoId=Q86VL8-4; Sequence=VSP_029658, VSP_029662;
Note=No experimental confirmation available.;
Name=5;
IsoId=Q86VL8-5; Sequence=VSP_029658, VSP_029660, VSP_029661;
Note=No experimental confirmation available.;
Name=6; Synonyms=MATE2-B;
IsoId=Q86VL8-6; Sequence=VSP_029657, VSP_029659;
Note=Inactive. Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Isoform 3 is predominantly expressed in
kidney. Isoform 6 is expressed in brain.
{ECO:0000269|PubMed:16807400}.
-!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE)
(TC 2.A.66.1) family. {ECO:0000305}.
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EMBL; AB250364; BAF36847.1; -; mRNA.
EMBL; AB250701; BAF37007.1; -; mRNA.
EMBL; AK055758; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; BX648861; CAH56154.1; -; mRNA.
EMBL; CH471212; EAW50902.1; -; Genomic_DNA.
EMBL; CH471212; EAW50904.1; -; Genomic_DNA.
EMBL; CH471212; EAW50905.1; -; Genomic_DNA.
EMBL; BC035288; AAH35288.1; -; mRNA.
EMBL; BC050578; AAH50578.1; -; mRNA.
CCDS; CCDS11211.1; -. [Q86VL8-1]
CCDS; CCDS58530.1; -. [Q86VL8-4]
RefSeq; NP_001093116.1; NM_001099646.1. [Q86VL8-3]
RefSeq; NP_001243592.1; NM_001256663.1. [Q86VL8-4]
RefSeq; NP_690872.2; NM_152908.3. [Q86VL8-1]
UniGene; Hs.126830; -.
ProteinModelPortal; Q86VL8; -.
STRING; 9606.ENSP00000326671; -.
BindingDB; Q86VL8; -.
ChEMBL; CHEMBL1743127; -.
DrugBank; DB00787; Aciclovir.
GuidetoPHARMACOLOGY; 1217; -.
TCDB; 2.A.66.1.20; the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.
iPTMnet; Q86VL8; -.
PhosphoSitePlus; Q86VL8; -.
BioMuta; SLC47A2; -.
DMDM; 74727585; -.
PaxDb; Q86VL8; -.
PeptideAtlas; Q86VL8; -.
PRIDE; Q86VL8; -.
Ensembl; ENST00000325411; ENSP00000326671; ENSG00000180638. [Q86VL8-1]
Ensembl; ENST00000350657; ENSP00000338084; ENSG00000180638. [Q86VL8-4]
Ensembl; ENST00000574239; ENSP00000458694; ENSG00000180638. [Q86VL8-6]
GeneID; 146802; -.
KEGG; hsa:146802; -.
UCSC; uc002gwe.5; human. [Q86VL8-1]
CTD; 146802; -.
DisGeNET; 146802; -.
EuPathDB; HostDB:ENSG00000180638.17; -.
GeneCards; SLC47A2; -.
H-InvDB; HIX0039367; -.
HGNC; HGNC:26439; SLC47A2.
MIM; 609833; gene.
neXtProt; NX_Q86VL8; -.
OpenTargets; ENSG00000180638; -.
PharmGKB; PA162403847; -.
eggNOG; KOG1347; Eukaryota.
eggNOG; COG0534; LUCA.
GeneTree; ENSGT00390000015713; -.
HOGENOM; HOG000060313; -.
HOVERGEN; HBG056043; -.
InParanoid; Q86VL8; -.
KO; K03327; -.
OMA; VCVRVGT; -.
OrthoDB; EOG091G06X2; -.
PhylomeDB; Q86VL8; -.
TreeFam; TF324441; -.
Reactome; R-HSA-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
GeneWiki; SLC47A2; -.
GenomeRNAi; 146802; -.
PRO; PR:Q86VL8; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000180638; -.
CleanEx; HS_SLC47A2; -.
ExpressionAtlas; Q86VL8; baseline and differential.
Genevisible; Q86VL8; HS.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0015238; F:drug transmembrane transporter activity; IBA:GO_Central.
GO; GO:0015307; F:drug:proton antiporter activity; TAS:Reactome.
GO; GO:0006855; P:drug transmembrane 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;
Alternative splicing; Cell membrane; Complete proteome; Membrane;
Polymorphism; Reference proteome; Transmembrane; Transmembrane helix;
Transport.
CHAIN 1 602 Multidrug and toxin extrusion protein 2.
/FTId=PRO_0000311952.
TOPO_DOM 1 33 Cytoplasmic. {ECO:0000255}.
TRANSMEM 34 54 Helical. {ECO:0000255}.
TOPO_DOM 55 66 Extracellular. {ECO:0000255}.
TRANSMEM 67 87 Helical. {ECO:0000255}.
TOPO_DOM 88 119 Cytoplasmic. {ECO:0000255}.
TRANSMEM 120 140 Helical. {ECO:0000255}.
TOPO_DOM 141 153 Extracellular. {ECO:0000255}.
TRANSMEM 154 174 Helical. {ECO:0000255}.
TOPO_DOM 175 219 Cytoplasmic. {ECO:0000255}.
TRANSMEM 220 240 Helical. {ECO:0000255}.
TOPO_DOM 241 248 Extracellular. {ECO:0000255}.
TRANSMEM 249 269 Helical. {ECO:0000255}.
TOPO_DOM 270 289 Cytoplasmic. {ECO:0000255}.
TRANSMEM 290 309 Helical. {ECO:0000255}.
TOPO_DOM 310 327 Extracellular. {ECO:0000255}.
TRANSMEM 328 348 Helical. {ECO:0000255}.
TOPO_DOM 349 368 Cytoplasmic. {ECO:0000255}.
TRANSMEM 369 389 Helical. {ECO:0000255}.
TOPO_DOM 390 402 Extracellular. {ECO:0000255}.
TRANSMEM 403 423 Helical. {ECO:0000255}.
TOPO_DOM 424 442 Cytoplasmic. {ECO:0000255}.
TRANSMEM 443 463 Helical. {ECO:0000255}.
TOPO_DOM 464 466 Extracellular. {ECO:0000255}.
TRANSMEM 467 487 Helical. {ECO:0000255}.
TOPO_DOM 488 578 Cytoplasmic. {ECO:0000255}.
TRANSMEM 579 599 Helical. {ECO:0000255}.
TOPO_DOM 600 602 Extracellular. {ECO:0000255}.
COMPBIAS 508 511 Poly-Gln.
VAR_SEQ 1 49 Missing (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_029656.
VAR_SEQ 178 219 GWLKGQEEESPFQTPGLSILHPSHSHLSRASFHLFQKITWP
Q -> AGERLCVPASSNSSTGMAEGAGGGVPIPNPGFVHPP
SISLTP (in isoform 6).
{ECO:0000303|PubMed:16807400}.
/FTId=VSP_029657.
VAR_SEQ 178 213 Missing (in isoform 2, isoform 3, isoform
4 and isoform 5).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:16807400,
ECO:0000303|PubMed:17974005}.
/FTId=VSP_029658.
VAR_SEQ 220 602 Missing (in isoform 6).
{ECO:0000303|PubMed:16807400}.
/FTId=VSP_029659.
VAR_SEQ 317 398 GLLSVVDLSAQAVIYEVATVTYMIPLGLSIGVCVRVGMALG
AADTVQAKRSAVSGVLSIVGISLVLGTLISILKNQLGHIFT
-> EHAQCGGSLCPGCHLGGHCDLHDSLGAQHRGLCPSGDG
SGGRGYCAGQALGRLGRAQHSWHFPGPGHPDKHPEKSAGAY
FYQ (in isoform 5).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_029660.
VAR_SEQ 339 339 M -> MRHSHRLAYAAHVTR (in isoform 4).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_029662.
VAR_SEQ 376 381 VGISLV -> EMSLPW (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_029663.
VAR_SEQ 382 602 Missing (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_029664.
VAR_SEQ 399 602 Missing (in isoform 5).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_029661.
VARIANT 429 429 G -> R (in dbSNP:rs34399035).
/FTId=VAR_037358.
CONFLICT 6 6 D -> E (in Ref. 1; BAF37007).
{ECO:0000305}.
CONFLICT 23 23 V -> A (in Ref. 2; AK055758).
{ECO:0000305}.
CONFLICT 93 93 D -> G (in Ref. 2; AK055758).
{ECO:0000305}.
CONFLICT 284 284 C -> Y (in Ref. 3; CAH56154).
{ECO:0000305}.
SEQUENCE 602 AA; 65085 MW; 88EB90286AE701D1 CRC64;
MDSLQDTVAL DHGGCCPALS RLVPRGFGTE MWTLFALSGP LFLFQVLTFM IYIVSTVFCG
HLGKVELASV TLAVAFVNVC GVSVGVGLSS ACDTLMSQSF GSPNKKHVGV ILQRGALVLL
LCCLPCWALF LNTQHILLLF RQDPDVSRLT QDYVMIFIPG LPVIFLYNLL AKYLQNQGWL
KGQEEESPFQ TPGLSILHPS HSHLSRASFH LFQKITWPQV LSGVVGNCVN GVANYALVSV
LNLGVRGSAY ANIISQFAQT VFLLLYIVLK KLHLETWAGW SSQCLQDWGP FFSLAVPSML
MICVEWWAYE IGSFLMGLLS VVDLSAQAVI YEVATVTYMI PLGLSIGVCV RVGMALGAAD
TVQAKRSAVS GVLSIVGISL VLGTLISILK NQLGHIFTND EDVIALVSQV LPVYSVFHVF
EAICCVYGGV LRGTGKQAFG AAVNAITYYI IGLPLGILLT FVVRMRIMGL WLGMLACVFL
ATAAFVAYTA RLDWKLAAEE AKKHSGRQQQ QRAESTATRP GPEKAVLSSV ATGSSPGITL
TTYSRSECHV DFFRTPEEAH ALSAPTSRLS VKQLVIRRGA ALGAASATLM VGLTVRILAT
RH


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EIAAB36696 OCT1,Organic cation transporter 1,Pig,pOCT1,SLC22A1,Solute carrier family 22 member 1,Sus scrofa


 

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