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Q86VL8 (S47A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Multidrug and toxin extrusion protein 2

Short name=MATE-2
Short name=hMATE-2
Alternative name(s):
Kidney-specific H(+)/organic cation antiporter
Solute carrier family 47 member 2
Gene names
Name:SLC47A2
Synonyms:MATE2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length602 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.6 Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein Potential. Note: Localized at the brush border membranes of the proximal tubules.

Tissue specificity

Isoform 3 is predominantly expressed in kidney. Isoform 6 is expressed in brain. Ref.1

Sequence similarities

Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family. [View classification]

Biophysicochemical properties

Kinetic parameters:

KM=0.76 mM for TEA Ref.1 Ref.7

KM=0.11 mM for MPP

KM=0.12 mM for cimetidine

KM=1.98 mM for metformin

KM=4.2 mM for guanidine

KM=1.58 mM for procainamide

KM=0.06 mM for topotecan

KM=0.85 mM for estrone sulfate

KM=4.32 mM for acyclovir

KM=4.28 mM for ganciclovir

Vmax=0.88 nmol/min/mg enzyme toward TEA

Vmax=0.575 nmol/min/mg enzyme toward MPP

Vmax=0.115 nmol/min/mg enzyme toward cimetidine

Vmax=0.845 nmol/min/mg enzyme toward metformin

Vmax=0.58 nmol/min/mg enzyme toward guanidine

Vmax=3.385 nmol/min/mg enzyme toward procainamide

Vmax=0.13 nmol/min/mg enzyme toward topotecan

Vmax=0.425 nmol/min/mg enzyme toward estrone sulfate

Vmax=0.945 nmol/min/mg enzyme toward acyclovir

Vmax=0.805 nmol/min/mg enzyme toward ganciclovir

pH dependence:

Optimum pH is 9.0. Active from pH 6 to 9.

Ontologies

Keywords
   Biological processTransport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processtransmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionantiporter activity

Inferred from electronic annotation. Source: InterPro

drug transmembrane transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q86VL8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q86VL8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
     178-213: Missing.
     376-381: VGISLV → EMSLPW
     382-602: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q86VL8-3)

Also known as: MATE2-K;

The sequence of this isoform differs from the canonical sequence as follows:
     178-213: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q86VL8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     178-213: Missing.
     339-339: M → MRHSHRLAYAAHVTR
Note: No experimental confirmation available.
Isoform 5 (identifier: Q86VL8-5)

The sequence of this isoform differs from the canonical sequence as follows:
     178-213: Missing.
     317-398: GLLSVVDLSA...LKNQLGHIFT → EHAQCGGSLC...EKSAGAYFYQ
     399-602: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q86VL8-6)

Also known as: MATE2-B;

The sequence of this isoform differs from the canonical sequence as follows:
     178-219: GWLKGQEEES...HLFQKITWPQ → AGERLCVPAS...VHPPSISLTP
     220-602: Missing.
Note: Inactive. Note=No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 602602Multidrug and toxin extrusion protein 2
PRO_0000311952

Regions

Topological domain1 – 3333Cytoplasmic Potential
Transmembrane34 – 5421Helical; Potential
Topological domain55 – 6612Extracellular Potential
Transmembrane67 – 8721Helical; Potential
Topological domain88 – 11932Cytoplasmic Potential
Transmembrane120 – 14021Helical; Potential
Topological domain141 – 15313Extracellular Potential
Transmembrane154 – 17421Helical; Potential
Topological domain175 – 21945Cytoplasmic Potential
Transmembrane220 – 24021Helical; Potential
Topological domain241 – 2488Extracellular Potential
Transmembrane249 – 26921Helical; Potential
Topological domain270 – 28920Cytoplasmic Potential
Transmembrane290 – 30920Helical; Potential
Topological domain310 – 32718Extracellular Potential
Transmembrane328 – 34821Helical; Potential
Topological domain349 – 36820Cytoplasmic Potential
Transmembrane369 – 38921Helical; Potential
Topological domain390 – 40213Extracellular Potential
Transmembrane403 – 42321Helical; Potential
Topological domain424 – 44219Cytoplasmic Potential
Transmembrane443 – 46321Helical; Potential
Topological domain464 – 4663Extracellular Potential
Transmembrane467 – 48721Helical; Potential
Topological domain488 – 57891Cytoplasmic Potential
Transmembrane579 – 59921Helical; Potential
Topological domain600 – 6023Extracellular Potential
Compositional bias508 – 5114Poly-Gln

Natural variations

Alternative sequence1 – 4949Missing in isoform 2.
VSP_029656
Alternative sequence178 – 21942GWLKG…ITWPQ → AGERLCVPASSNSSTGMAEG AGGGVPIPNPGFVHPPSISL TP in isoform 6.
VSP_029657
Alternative sequence178 – 21336Missing in isoform 2, isoform 3, isoform 4 and isoform 5.
VSP_029658
Alternative sequence220 – 602383Missing in isoform 6.
VSP_029659
Alternative sequence317 – 39882GLLSV…GHIFT → EHAQCGGSLCPGCHLGGHCD LHDSLGAQHRGLCPSGDGSG GRGYCAGQALGRLGRAQHSW HFPGPGHPDKHPEKSAGAYF YQ in isoform 5.
VSP_029660
Alternative sequence3391M → MRHSHRLAYAAHVTR in isoform 4.
VSP_029662
Alternative sequence376 – 3816VGISLV → EMSLPW in isoform 2.
VSP_029663
Alternative sequence382 – 602221Missing in isoform 2.
VSP_029664
Alternative sequence399 – 602204Missing in isoform 5.
VSP_029661
Natural variant4291G → R.
Corresponds to variant rs34399035 [ dbSNP | Ensembl ].
VAR_037358

Experimental info

Sequence conflict61D → E in BAF37007. Ref.1
Sequence conflict231V → A in AK055758. Ref.2
Sequence conflict931D → G in AK055758. Ref.2
Sequence conflict2841C → Y in CAH56154. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 88EB90286AE701D1

FASTA60265,085
        10         20         30         40         50         60 
MDSLQDTVAL DHGGCCPALS RLVPRGFGTE MWTLFALSGP LFLFQVLTFM IYIVSTVFCG 

        70         80         90        100        110        120 
HLGKVELASV TLAVAFVNVC GVSVGVGLSS ACDTLMSQSF GSPNKKHVGV ILQRGALVLL 

       130        140        150        160        170        180 
LCCLPCWALF LNTQHILLLF RQDPDVSRLT QDYVMIFIPG LPVIFLYNLL AKYLQNQGWL 

       190        200        210        220        230        240 
KGQEEESPFQ TPGLSILHPS HSHLSRASFH LFQKITWPQV LSGVVGNCVN GVANYALVSV 

       250        260        270        280        290        300 
LNLGVRGSAY ANIISQFAQT VFLLLYIVLK KLHLETWAGW SSQCLQDWGP FFSLAVPSML 

       310        320        330        340        350        360 
MICVEWWAYE IGSFLMGLLS VVDLSAQAVI YEVATVTYMI PLGLSIGVCV RVGMALGAAD 

       370        380        390        400        410        420 
TVQAKRSAVS GVLSIVGISL VLGTLISILK NQLGHIFTND EDVIALVSQV LPVYSVFHVF 

       430        440        450        460        470        480 
EAICCVYGGV LRGTGKQAFG AAVNAITYYI IGLPLGILLT FVVRMRIMGL WLGMLACVFL 

       490        500        510        520        530        540 
ATAAFVAYTA RLDWKLAAEE AKKHSGRQQQ QRAESTATRP GPEKAVLSSV ATGSSPGITL 

       550        560        570        580        590        600 
TTYSRSECHV DFFRTPEEAH ALSAPTSRLS VKQLVIRRGA ALGAASATLM VGLTVRILAT 


RH 

« Hide

Isoform 2 [UniParc].

Checksum: A8233F83A55432EC
Show »

FASTA29632,120
Isoform 3 (MATE2-K) [UniParc].

Checksum: A3D0B0E578E0B8C2
Show »

FASTA56661,016
Isoform 4 [UniParc].

Checksum: 848F216F93C7F1C7
Show »

FASTA58062,673
Isoform 5 [UniParc].

Checksum: 35A2CE7A78E3E19D
Show »

FASTA36239,287
Isoform 6 (MATE2-B) [UniParc].

Checksum: 40D6F1AA297DAA91
Show »

FASTA21923,344

References

« Hide 'large scale' references
[1]"Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2."
Masuda S., Terada T., Yonezawa A., Tanihara Y., Kishimoto K., Katsura T., Ogawa O., Inui K.
J. Am. Soc. Nephrol. 17:2127-2135(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 6), TISSUE SPECIFICITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Brain and Kidney.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Kidney.
[3]"The full-ORF clone resource of the German cDNA consortium."
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.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Small intestine.
[4]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORMS 1 AND 4).
Tissue: Colon.
[6]"The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations."
Omote H., Hiasa M., Matsumoto T., Otsuka M., Moriyama Y.
Trends Pharmacol. Sci. 27:587-593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters."
Tanihara Y., Masuda S., Sato T., Katsura T., Ogawa O., Inui K.
Biochem. Pharmacol. 74:359-371(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB250364 mRNA. Translation: BAF36847.1.
AB250701 mRNA. Translation: BAF37007.1.
AK055758 mRNA. No translation available.
BX648861 mRNA. Translation: CAH56154.1.
CH471212 Genomic DNA. Translation: EAW50902.1.
CH471212 Genomic DNA. Translation: EAW50904.1.
CH471212 Genomic DNA. Translation: EAW50905.1.
BC035288 mRNA. Translation: AAH35288.1.
BC050578 mRNA. Translation: AAH50578.1.
CCDSCCDS11211.1. [Q86VL8-1]
CCDS58530.1. [Q86VL8-4]
RefSeqNP_001093116.1. NM_001099646.1. [Q86VL8-3]
NP_001243592.1. NM_001256663.1. [Q86VL8-4]
NP_690872.2. NM_152908.3. [Q86VL8-1]
UniGeneHs.126830.

3D structure databases

ProteinModelPortalQ86VL8.
SMRQ86VL8. Positions 19-506.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4723030.
STRING9606.ENSP00000326671.

Chemistry

ChEMBLCHEMBL1743127.
GuidetoPHARMACOLOGY1217.

Protein family/group databases

TCDB2.A.66.1.20. the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.

PTM databases

PhosphoSiteQ86VL8.

Polymorphism databases

DMDM74727585.

Proteomic databases

PaxDbQ86VL8.
PRIDEQ86VL8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000325411; ENSP00000326671; ENSG00000180638. [Q86VL8-1]
ENST00000350657; ENSP00000338084; ENSG00000180638. [Q86VL8-4]
ENST00000574239; ENSP00000458694; ENSG00000180638. [Q86VL8-6]
GeneID146802.
KEGGhsa:146802.
UCSCuc002gwe.4. human. [Q86VL8-1]
uc002gwf.4. human. [Q86VL8-4]
uc002gwg.4. human. [Q86VL8-3]

Organism-specific databases

CTD146802.
GeneCardsGC17M019582.
H-InvDBHIX0039367.
HGNCHGNC:26439. SLC47A2.
HPAHPA044412.
MIM609833. gene.
neXtProtNX_Q86VL8.
PharmGKBPA162403847.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0534.
HOGENOMHOG000060313.
HOVERGENHBG056043.
InParanoidQ86VL8.
KOK03327.
OMACEPTKVT.
OrthoDBEOG7RRF71.
PhylomeDBQ86VL8.
TreeFamTF324441.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_20633. Bile salt and organic anion SLC transporters.

Gene expression databases

ArrayExpressQ86VL8.
BgeeQ86VL8.
CleanExHS_SLC47A2.
GenevestigatorQ86VL8.

Family and domain databases

InterProIPR002528. MATE.
[Graphical view]
PfamPF01554. MatE. 2 hits.
[Graphical view]
TIGRFAMsTIGR00797. matE. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC47A2.
GenomeRNAi146802.
NextBio85455.
PROQ86VL8.
SOURCESearch...

Entry information

Entry nameS47A2_HUMAN
AccessionPrimary (citable) accession number: Q86VL8
Secondary accession number(s): A0JBX9 expand/collapse secondary AC list , A0P8Z7, Q63HJ9, Q8IV44, Q96NA1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2003
Last modified: July 9, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM