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Q96FL8

- S47A1_HUMAN

UniProt

Q96FL8 - S47A1_HUMAN

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Protein
Multidrug and toxin extrusion protein 1
Gene
SLC47A1, MATE1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.5 Publications

Kineticsi

  1. KM=0.38 mM for TEA2 Publications
  2. KM=0.10 mM for MPP
  3. KM=0.17 mM for cimetidine
  4. KM=0.78 mM for metformin
  5. KM=2.1 mM for guanidine
  6. KM=1.23 mM for procainamide
  7. KM=0.07 mM for topotecan
  8. KM=0.47 mM for estrone sulfate
  9. KM=2.64 mM for acyclovir
  10. KM=5.12 mM for ganciclovir

Vmax=1.185 nmol/min/mg enzyme toward TEA

Vmax=0.735 nmol/min/mg enzyme toward MPP

Vmax=0.135 nmol/min/mg enzyme toward cimetidine

Vmax=2.23 nmol/min/mg enzyme toward metformin

Vmax=0.89 nmol/min/mg enzyme toward guanidine

Vmax=3.78 nmol/min/mg enzyme toward procainamide

Vmax=0.21 nmol/min/mg enzyme toward topotecan

Vmax=0.265 nmol/min/mg enzyme toward estrone sulfate

Vmax=0.62 nmol/min/mg enzyme toward acyclovir

Vmax=1.08 nmol/min/mg enzyme toward ganciclovir

pH dependencei

Optimum pH is 8.5. Active from pH 6 to 8.5.

GO - Molecular functioni

  1. drug transmembrane transporter activity Source: Ensembl
  2. monovalent cation:proton antiporter activity Source: Ensembl

GO - Biological processi

  1. organic cation transport Source: Ensembl
  2. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiREACT_19305. Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds.

Protein family/group databases

TCDBi2.A.66.1.14. 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:
hMATE-1
Alternative name(s):
Solute carrier family 47 member 1
Gene namesi
Name:SLC47A1
Synonyms:MATE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:25588. SLC47A1.

Subcellular locationi

Cell membrane; Multi-pass membrane protein
Note: Predominantly localized at the plasma membrane but also found in intracellular organelles.2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei38 – 5821Helical; Reviewed prediction
Add
BLAST
Topological domaini59 – 7214Extracellular Reviewed prediction
Add
BLAST
Transmembranei73 – 9321Helical; Reviewed prediction
Add
BLAST
Topological domaini94 – 12330Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei124 – 14421Helical; Reviewed prediction
Add
BLAST
Topological domaini145 – 1528Extracellular Reviewed prediction
Transmembranei153 – 17321Helical; Reviewed prediction
Add
BLAST
Topological domaini174 – 1763Cytoplasmic Reviewed prediction
Transmembranei177 – 19721Helical; Reviewed prediction
Add
BLAST
Topological domaini198 – 21619Extracellular Reviewed prediction
Add
BLAST
Transmembranei217 – 23721Helical; Reviewed prediction
Add
BLAST
Topological domaini238 – 25619Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei257 – 27620Helical; Reviewed prediction
Add
BLAST
Topological domaini277 – 29519Extracellular Reviewed prediction
Add
BLAST
Transmembranei296 – 31621Helical; Reviewed prediction
Add
BLAST
Topological domaini317 – 33620Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei337 – 35721Helical; Reviewed prediction
Add
BLAST
Topological domaini358 – 37013Extracellular Reviewed prediction
Add
BLAST
Transmembranei371 – 39121Helical; Reviewed prediction
Add
BLAST
Topological domaini392 – 40817Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei409 – 42921Helical; Reviewed prediction
Add
BLAST
Topological domaini430 – 4378Extracellular Reviewed prediction
Transmembranei438 – 45821Helical; Reviewed prediction
Add
BLAST
Topological domaini459 – 54688Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei547 – 56721Helical; Reviewed prediction
Add
BLAST
Topological domaini568 – 5703Extracellular Reviewed prediction

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. membrane-bounded vesicle Source: Ensembl
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi273 – 2731E → Q: No change in subcellular location and abolition of MATE1-dependent TEA transport activity. 1 Publication

Organism-specific databases

PharmGKBiPA162403808.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 570570Multidrug and toxin extrusion protein 1
PRO_0000312845Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ96FL8.
PaxDbiQ96FL8.
PRIDEiQ96FL8.

PTM databases

PhosphoSiteiQ96FL8.

Expressioni

Tissue specificityi

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).2 Publications

Gene expression databases

ArrayExpressiQ96FL8.
BgeeiQ96FL8.
CleanExiHS_SLC47A1.
GenevestigatoriQ96FL8.

Organism-specific databases

HPAiHPA021987.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000270570.

Structurei

3D structure databases

ProteinModelPortaliQ96FL8.
SMRiQ96FL8. Positions 28-454.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0534.
HOGENOMiHOG000060313.
HOVERGENiHBG056043.
KOiK03327.
OMAiFPRYLVM.
OrthoDBiEOG7RRF71.
PhylomeDBiQ96FL8.
TreeFamiTF324441.

Family and domain databases

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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q96FL8-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEAPEEPAPV RGGPEATLEV RGSRCLRLSA FREELRALLV LAGPAFLVQL    50
MVFLISFISS VFCGHLGKLE LDAVTLAIAV INVTGVSVGF GLSSACDTLI 100
SQTYGSQNLK HVGVILQRSA LVLLLCCFPC WALFLNTQHI LLLFRQDPDV 150
SRLTQTYVTI FIPALPATFL YMLQVKYLLN QGIVLPQIVT GVAANLVNAL 200
ANYLFLHQLH LGVIGSALAN LISQYTLALL LFLYILGKKL HQATWGGWSL 250
ECLQDWASFL RLAIPSMLML CMEWWAYEVG SFLSGILGMV ELGAQSIVYE 300
LAIIVYMVPA GFSVAASVRV GNALGAGDME QARKSSTVSL LITVLFAVAF 350
SVLLLSCKDH VGYIFTTDRD IINLVAQVVP IYAVSHLFEA LACTSGGVLR 400
GSGNQKVGAI VNTIGYYVVG LPIGIALMFA TTLGVMGLWS GIIICTVFQA 450
VCFLGFIIQL NWKKACQQAQ VHANLKVNNV PRSGNSALPQ DPLHPGCPEN 500
LEGILTNDVG KTGEPQSDQQ MRQEEPLPEH PQDGAKLSRK QLVLRRGLLL 550
LGVFLILLVG ILVRFYVRIQ 570
Length:570
Mass (Da):61,922
Last modified:December 1, 2001 - v1
Checksum:iCA940CBC2F6F5CC4
GO
Isoform 2 (identifier: Q96FL8-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-290: ILGMV → LYEDG
     291-570: Missing.

Note: No experimental confirmation available.

Show »
Length:290
Mass (Da):31,907
Checksum:i662AE04699124D14
GO
Isoform 3 (identifier: Q96FL8-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     559-570: VGILVRFYVRIQ → AGVRWCDHSSLQPRTLGLQAILLCQPPE

Note: No experimental confirmation available.

Show »
Length:586
Mass (Da):63,549
Checksum:iA1BF0F64D815E7A8
GO

Sequence cautioni

The sequence AAH50592.1 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti338 – 3381V → I.
Corresponds to variant rs35790011 [ dbSNP | Ensembl ].
VAR_037587

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei286 – 2905ILGMV → LYEDG in isoform 2.
VSP_029903
Alternative sequencei291 – 570280Missing in isoform 2.
VSP_029904Add
BLAST
Alternative sequencei559 – 57012VGILV…YVRIQ → AGVRWCDHSSLQPRTLGLQA ILLCQPPE in isoform 3.
VSP_029905Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti50 – 501L → R in BAD96345. 1 Publication
Sequence conflicti309 – 3091P → L in BAA91852. 1 Publication
Sequence conflicti448 – 4481F → L in BAD96345. 1 Publication
Sequence conflicti507 – 5071N → D in BAD96345. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AK001709 mRNA. Translation: BAA91852.1.
AK222625 mRNA. Translation: BAD96345.1.
CH471212 Genomic DNA. Translation: EAW50893.1.
CH471212 Genomic DNA. Translation: EAW50894.1.
BC010661 mRNA. Translation: AAH10661.1.
BC050592 mRNA. Translation: AAH50592.1. Different initiation.
BC058882 mRNA. Translation: AAH58882.1.
CCDSiCCDS11209.1. [Q96FL8-1]
RefSeqiNP_060712.2. NM_018242.2. [Q96FL8-1]
UniGeneiHs.232054.

Genome annotation databases

EnsembliENST00000270570; ENSP00000270570; ENSG00000142494. [Q96FL8-1]
ENST00000395585; ENSP00000378951; ENSG00000142494. [Q96FL8-3]
ENST00000457293; ENSP00000415586; ENSG00000142494. [Q96FL8-3]
GeneIDi55244.
KEGGihsa:55244.
UCSCiuc002gvx.3. human. [Q96FL8-3]
uc002gvy.1. human. [Q96FL8-1]

Polymorphism databases

DMDMi74731723.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AK001709 mRNA. Translation: BAA91852.1 .
AK222625 mRNA. Translation: BAD96345.1 .
CH471212 Genomic DNA. Translation: EAW50893.1 .
CH471212 Genomic DNA. Translation: EAW50894.1 .
BC010661 mRNA. Translation: AAH10661.1 .
BC050592 mRNA. Translation: AAH50592.1 . Different initiation.
BC058882 mRNA. Translation: AAH58882.1 .
CCDSi CCDS11209.1. [Q96FL8-1 ]
RefSeqi NP_060712.2. NM_018242.2. [Q96FL8-1 ]
UniGenei Hs.232054.

3D structure databases

ProteinModelPortali Q96FL8.
SMRi Q96FL8. Positions 28-454.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000270570.

Chemistry

ChEMBLi CHEMBL1743126.
GuidetoPHARMACOLOGYi 1216.

Protein family/group databases

TCDBi 2.A.66.1.14. the multidrug/oligosaccharidyl-lipid/polysaccharide (mop) flippase superfamily.

PTM databases

PhosphoSitei Q96FL8.

Polymorphism databases

DMDMi 74731723.

Proteomic databases

MaxQBi Q96FL8.
PaxDbi Q96FL8.
PRIDEi Q96FL8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000270570 ; ENSP00000270570 ; ENSG00000142494 . [Q96FL8-1 ]
ENST00000395585 ; ENSP00000378951 ; ENSG00000142494 . [Q96FL8-3 ]
ENST00000457293 ; ENSP00000415586 ; ENSG00000142494 . [Q96FL8-3 ]
GeneIDi 55244.
KEGGi hsa:55244.
UCSCi uc002gvx.3. human. [Q96FL8-3 ]
uc002gvy.1. human. [Q96FL8-1 ]

Organism-specific databases

CTDi 55244.
GeneCardsi GC17P019398.
H-InvDB HIX0013619.
HGNCi HGNC:25588. SLC47A1.
HPAi HPA021987.
MIMi 609832. gene.
neXtProti NX_Q96FL8.
PharmGKBi PA162403808.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0534.
HOGENOMi HOG000060313.
HOVERGENi HBG056043.
KOi K03327.
OMAi FPRYLVM.
OrthoDBi EOG7RRF71.
PhylomeDBi Q96FL8.
TreeFami TF324441.

Enzyme and pathway databases

Reactomei REACT_19305. Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds.

Miscellaneous databases

GeneWikii SLC47A1.
GenomeRNAii 55244.
NextBioi 59282.
PROi Q96FL8.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q96FL8.
Bgeei Q96FL8.
CleanExi HS_SLC47A1.
Genevestigatori Q96FL8.

Family and domain databases

InterProi IPR002528. MATE.
[Graphical view ]
Pfami PF01554. MatE. 2 hits.
[Graphical view ]
TIGRFAMsi TIGR00797. matE. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "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.
    , 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 1).
  2. 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
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Cerebellum.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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; 2 AND 3).
    Tissue: Colon and Eye.
  5. "A human transporter protein that mediates the final excretion step for toxic organic cations."
    Otsuka M., Matsumoto T., Morimoto R., Arioka S., Omote H., Moriyama Y.
    Proc. Natl. Acad. Sci. U.S.A. 102:17923-17928(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-273, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
  6. "Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations."
    Hiasa M., Matsumoto T., Komatsu T., Moriyama Y.
    Am. J. Physiol. 291:C678-C686(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "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.
  8. "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, TISSUE SPECIFICITY.
  9. "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.
  10. "Transport of paraquat by human organic cation transporters and multidrug and toxic compound extrusion family."
    Chen Y., Zhang S., Sorani M., Giacomini K.M.
    J. Pharmacol. Exp. Ther. 322:695-700(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiS47A1_HUMAN
AccessioniPrimary (citable) accession number: Q96FL8
Secondary accession number(s): Q53HF5
, Q6PD77, Q86VL4, Q9NVA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: December 1, 2001
Last modified: September 3, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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