GTR9_HUMAN
ID GTR9_HUMAN Reviewed; 540 AA.
AC Q9NRM0; Q0VGC4; Q4W5D1; Q8WV30; Q96P00;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Solute carrier family 2, facilitated glucose transporter member 9 {ECO:0000305};
DE AltName: Full=Glucose transporter type 9 {ECO:0000303|PubMed:10860667};
DE Short=GLUT-9 {ECO:0000303|PubMed:10860667};
DE AltName: Full=Urate transporter {ECO:0000305};
GN Name=SLC2A9 {ECO:0000303|PubMed:10860667, ECO:0000312|HGNC:HGNC:13446};
GN Synonyms=GLUT9 {ECO:0000303|PubMed:10860667};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-25 AND LEU-350.
RC TISSUE=Kidney;
RX PubMed=10860667; DOI=10.1006/geno.2000.6195;
RA Phay J.E., Hussain H.B., Moley J.F.;
RT "Cloning and expression analysis of a novel member of the facilitative
RT glucose transporter family, SLC2A9 (GLUT9).";
RL Genomics 66:217-220(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP ARG-25 AND LEU-350.
RC TISSUE=Lung, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-238 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Articular cartilage;
RX PubMed=11991658; DOI=10.1006/cbir.2001.0850;
RA Mobasheri A., Neama G., Bell S., Richardson S., Carter S.D.;
RT "Human articular chondrocytes express three facilitative glucose
RT transporter isoforms: GLUT1, GLUT3 and GLUT9.";
RL Cell Biol. Int. 26:297-300(2002).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=14739288; DOI=10.1074/jbc.m312226200;
RA Augustin R., Carayannopoulos M.O., Dowd L.O., Phay J.E., Moley J.F.,
RA Moley K.H.;
RT "Identification and characterization of human glucose transporter-like
RT protein-9 (GLUT9): alternative splicing alters trafficking.";
RL J. Biol. Chem. 279:16229-16236(2004).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARACTERIZATION OF VARIANT VAL-296.
RX PubMed=17710649; DOI=10.1080/09687680701298143;
RA Manolescu A.R., Augustin R., Moley K., Cheeseman C.;
RT "A highly conserved hydrophobic motif in the exofacial vestibule of
RT fructose transporting SLC2A proteins acts as a critical determinant of
RT their substrate selectivity.";
RL Mol. Membr. Biol. 24:455-463(2007).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND POLYMORPHISM.
RX PubMed=18842065; DOI=10.1371/journal.pmed.0050197;
RA Caulfield M.J., Munroe P.B., O'Neill D., Witkowska K., Charchar F.J.,
RA Doblado M., Evans S., Eyheramendy S., Onipinla A., Howard P.,
RA Shaw-Hawkins S., Dobson R.J., Wallace C., Newhouse S.J., Brown M.,
RA Connell J.M., Dominiczak A., Farrall M., Lathrop G.M., Samani N.J.,
RA Kumari M., Marmot M., Brunner E., Chambers J., Elliott P., Kooner J.,
RA Laan M., Org E., Veldre G., Viigimaa M., Cappuccio F.P., Ji C., Iacone R.,
RA Strazzullo P., Moley K.H., Cheeseman C.;
RT "SLC2A9 is a high-capacity urate transporter in humans.";
RL PLoS Med. 5:e197-e197(2008).
RN [8]
RP FUNCTION, ALTERNATIVE SPLICING, BIOPHYSICOCHEMICAL PROPERTIES, TRANSPORTER
RP ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22647630; DOI=10.1152/ajprenal.00134.2012;
RA Witkowska K., Smith K.M., Yao S.Y., Ng A.M., O'Neill D., Karpinski E.,
RA Young J.D., Cheeseman C.I.;
RT "Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate
RT with different characteristics in the presence of hexoses.";
RL Am. J. Physiol. 303:F527-F539(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-515, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=24409316; DOI=10.1371/journal.pone.0084996;
RA Kimura T., Takahashi M., Yan K., Sakurai H.;
RT "Expression of SLC2A9 isoforms in the kidney and their localization in
RT polarized epithelial cells.";
RL PLoS ONE 9:E84996-E84996(2014).
RN [11]
RP FUNCTION, TRANSPORTER ACTIVITY, AND CAUTION.
RX PubMed=28083649; DOI=10.1007/s00232-016-9945-7;
RA Ebert K., Ludwig M., Geillinger K.E., Schoberth G.C., Essenwanger J.,
RA Stolz J., Daniel H., Witt H.;
RT "Reassessment of GLUT7 and GLUT9 as putative fructose and glucose
RT transporters.";
RL J. Membr. Biol. 250:171-182(2017).
RN [12]
RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF CYS-157; CYS-210;
RP CYS-326; CYS-330; LEU-332; CYS-427; CYS-480 AND CYS-488.
RX PubMed=28117388; DOI=10.1038/srep41167;
RA Long W., Panigrahi R., Panwar P., Wong K., O Neill D., Chen X.Z.,
RA Lemieux M.J., Cheeseman C.I.;
RT "Identification of Key Residues for Urate Specific Transport in Human
RT Glucose Transporter 9 (hSLC2A9).";
RL Sci. Rep. 7:41167-41167(2017).
RN [13]
RP VARIANTS RHUC2 CYS-198 AND TRP-380, AND CHARACTERIZATION OF VARIANTS RHUC2
RP CYS-198 AND TRP-380.
RX PubMed=19026395; DOI=10.1016/j.ajhg.2008.11.001;
RA Matsuo H., Chiba T., Nagamori S., Nakayama A., Domoto H., Phetdee K.,
RA Wiriyasermkul P., Kikuchi Y., Oda T., Nishiyama J., Nakamura T.,
RA Morimoto Y., Kamakura K., Sakurai Y., Nonoyama S., Kanai Y., Shinomiya N.;
RT "Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia.";
RL Am. J. Hum. Genet. 83:744-751(2008).
RN [14]
RP ERRATUM OF PUBMED:19026395.
RA Matsuo H., Chiba T., Nagamori S., Nakayama A., Domoto H., Phetdee K.,
RA Wiriyasermkul P., Kikuchi Y., Oda T., Nishiyama J., Nakamura T.,
RA Morimoto Y., Kamakura K., Sakurai Y., Nonoyama S., Kanai Y., Shinomiya N.;
RL Am. J. Hum. Genet. 83:795-795(2008).
RN [15]
RP VARIANT RHUC2 ARG-412, CHARACTERIZATION OF VARIANT RHUC2 ARG-412,
RP INVOLVEMENT IN RHUC2, FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18701466; DOI=10.1074/jbc.c800156200;
RA Anzai N., Ichida K., Jutabha P., Kimura T., Babu E., Jin C.J.,
RA Srivastava S., Kitamura K., Hisatome I., Endou H., Sakurai H.;
RT "Plasma urate level is directly regulated by a voltage-driven urate efflux
RT transporter URATv1 (SLC2A9) in humans.";
RL J. Biol. Chem. 283:26834-26838(2008).
RN [16]
RP INVOLVEMENT IN THE REGULATION OF SERUM URIC ACID CONCENTRATION, VARIANTS
RP ASP-191; HIS-281; ILE-282 AND LEU-350, AND POLYMORPHISM.
RX PubMed=18327256; DOI=10.1038/ng.107;
RA Doering A., Gieger C., Mehta D., Gohlke H., Prokisch H., Coassin S.,
RA Fischer G., Henke K., Klopp N., Kronenberg F., Paulweber B., Pfeufer A.,
RA Rosskopf D., Voelzke H., Illig T., Meitinger T., Wichmann H.-E.,
RA Meisinger C.;
RT "SLC2A9 influences uric acid concentrations with pronounced sex-specific
RT effects.";
RL Nat. Genet. 40:430-436(2008).
RN [17]
RP FUNCTION, POLYMORPHISM, VARIANTS ASN-22; ARG-216; MET-275; HIS-281 AND
RP HIS-300, CAUTION, AND TRANSPORTER ACTIVITY.
RX PubMed=18327257; DOI=10.1038/ng.106;
RA Vitart V., Rudan I., Hayward C., Gray N.K., Floyd J., Palmer C.N.,
RA Knott S.A., Kolcic I., Polasek O., Graessler J., Wilson J.F., Marinaki A.,
RA Riches P.L., Shu X., Janicijevic B., Smolej-Narancic N., Gorgoni B.,
RA Morgan J., Campbell S., Biloglav Z., Barac-Lauc L., Pericic M.,
RA Klaric I.M., Zgaga L., Skaric-Juric T., Wild S.H., Richardson W.A.,
RA Hohenstein P., Kimber C.H., Tenesa A., Donnelly L.A., Fairbanks L.D.,
RA Aringer M., McKeigue P.M., Ralston S.H., Morris A.D., Rudan P.,
RA Hastie N.D., Campbell H., Wright A.F.;
RT "SLC2A9 is a newly identified urate transporter influencing serum urate
RT concentration, urate excretion and gout.";
RL Nat. Genet. 40:437-442(2008).
RN [18]
RP VARIANT RHUC2 ARG-75, CHARACTERIZATION OF VARIANT RHUC2 ARG-75, AND
RP INVOLVEMENT IN RHUC2.
RX PubMed=19926891; DOI=10.1681/asn.2009040406;
RA Dinour D., Gray N.K., Campbell S., Shu X., Sawyer L., Richardson W.,
RA Rechavi G., Amariglio N., Ganon L., Sela B.A., Bahat H., Goldman M.,
RA Weissgarten J., Millar M.R., Wright A.F., Holtzman E.J.;
RT "Homozygous SLC2A9 mutations cause severe renal hypouricemia.";
RL J. Am. Soc. Nephrol. 21:64-72(2010).
RN [19]
RP VARIANTS RHUC2 CYS-198 AND TRP-380, CHARACTERIZATION OF VARIANTS RHUC2
RP CYS-198; TRP-380 AND ARG-412, AND INVOLVEMENT IN RHUC2.
RX PubMed=22132964; DOI=10.1080/15257770.2011.623685;
RA Kawamura Y., Matsuo H., Chiba T., Nagamori S., Nakayama A., Inoue H.,
RA Utsumi Y., Oda T., Nishiyama J., Kanai Y., Shinomiya N.;
RT "Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2).";
RL Nucleosides Nucleotides Nucleic Acids 30:1105-1111(2011).
RN [20]
RP VARIANTS RHUC2 MET-125 AND CYS-171, AND CHARACTERIZATION OF VARIANTS RHUC2
RP MET-125 AND CYS-171.
RX PubMed=21810765; DOI=10.1093/ndt/gfr419;
RA Dinour D., Gray N.K., Ganon L., Knox A.J., Shalev H., Sela B.A.,
RA Campbell S., Sawyer L., Shu X., Valsamidou E., Landau D., Wright A.F.,
RA Holtzman E.J.;
RT "Two novel homozygous SLC2A9 mutations cause renal hypouricemia type 2.";
RL Nephrol. Dial. Transplant. 27:1035-1041(2012).
RN [21]
RP VARIANTS RHUC2 ARG-216 AND SER-333, AND VARIANTS ILE-282; HIS-294 AND
RP LEU-350.
RX PubMed=22527535; DOI=10.1007/s00467-012-2174-0;
RA Stiburkova B., Taylor J., Marinaki A.M., Sebesta I.;
RT "Acute kidney injury in two children caused by renal hypouricaemia type
RT 2.";
RL Pediatr. Nephrol. 27:1411-1415(2012).
RN [22]
RP CHARACTERIZATION OF VARIANTS ARG-25; MET-169; MET-275; HIS-281; ILE-282;
RP HIS-294 AND LEU-350.
RX PubMed=25268603; DOI=10.1371/journal.pone.0107902;
RA Hurba O., Mancikova A., Krylov V., Pavlikova M., Pavelka K., Stiburkova B.;
RT "Complex analysis of urate transporters SLC2A9, SLC22A12 and functional
RT characterization of non-synonymous allelic variants of GLUT9 in the Czech
RT population: no evidence of effect on hyperuricemia and gout.";
RL PLoS ONE 9:E107902-E107902(2014).
RN [23]
RP FUNCTION, TRANSPORTER ACTIVITY, CHARACTERIZATION OF VARIANTS RHUC2 ARG-75;
RP MET-125; CYS-171; CYS-198; ARG-216; SER-333; TRP-380 AND ARG-412,
RP CHARACTERIZATION OF VARIANTS HIS-294; LEU-350 AND ILE-531, AND MUTAGENESIS
RP OF CYS-210.
RX PubMed=29967582; DOI=10.3389/fphys.2018.00476;
RA Ruiz A., Gautschi I., Schild L., Bonny O.;
RT "Human Mutations in SLC2A9 (Glut9) Affect Transport Capacity for Urate.";
RL Front. Physiol. 9:476-476(2018).
CC -!- FUNCTION: High-capacity urate transporter, which may play a role in the
CC urate reabsorption by proximal tubules (PubMed:18327257,
CC PubMed:28083649, PubMed:22647630, PubMed:18701466). May have a residual
CC high-affinity, low-capacity glucose and fructose transporter activity
CC (PubMed:18842065, PubMed:18327257, PubMed:18701466). Transports urate
CC at rates 45- to 60-fold faster than glucose (PubMed:18842065). Does not
CC transport galactose (PubMed:28083649). May mediate small uptake of
CC adenine but not of other nucleobases (PubMed:22647630).
CC {ECO:0000269|PubMed:18327257, ECO:0000269|PubMed:18701466,
CC ECO:0000269|PubMed:18842065, ECO:0000269|PubMed:22647630,
CC ECO:0000269|PubMed:28083649}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=urate(out) = urate(in); Xref=Rhea:RHEA:60368,
CC ChEBI:CHEBI:17775; Evidence={ECO:0000269|PubMed:18701466,
CC ECO:0000269|PubMed:18842065, ECO:0000269|PubMed:22647630,
CC ECO:0000269|PubMed:28083649, ECO:0000269|PubMed:28117388};
CC -!- ACTIVITY REGULATION: [Isoform 1]: Extracellular glucose and urate
CC accelerate urate efflux (PubMed:22647630, PubMed:18842065).
CC Intracellular urate, glucose and fructose accelerate urate influx
CC (PubMed:22647630). {ECO:0000269|PubMed:18842065,
CC ECO:0000269|PubMed:22647630}.
CC -!- ACTIVITY REGULATION: [Isoform 2]: No effect of extracellular urate,
CC glucose or fructose on urate efflux. Intracellular urate and fructose
CC slightly accelerate urate influx. {ECO:0000269|PubMed:22647630}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=900 uM for urate {ECO:0000269|PubMed:18327257,
CC ECO:0000269|PubMed:18842065};
CC KM=433 uM for urate {ECO:0000269|PubMed:29967582};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC Kinetic parameters:
CC KM=1 mM for urate influx {ECO:0000269|PubMed:22647630};
CC KM=1 mM for urate efflux {ECO:0000269|PubMed:22647630};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=1 mM for urate influx {ECO:0000269|PubMed:22647630};
CC KM=1 mM for urate efflux {ECO:0000269|PubMed:22647630};
CC -!- INTERACTION:
CC Q9NRM0-1; Q5J8M3: EMC4; NbExp=3; IntAct=EBI-25396304, EBI-2814031;
CC Q9NRM0-1; Q9Y287: ITM2B; NbExp=4; IntAct=EBI-25396304, EBI-2866431;
CC Q9NRM0-2; Q5J8M3: EMC4; NbExp=2; IntAct=EBI-25396386, EBI-2814031;
CC Q9NRM0-2; Q9Y287: ITM2B; NbExp=2; IntAct=EBI-25396386, EBI-2866431;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:18701466}; Multi-pass membrane protein. Basolateral
CC cell membrane {ECO:0000269|PubMed:14739288,
CC ECO:0000269|PubMed:24409316}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:14739288}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:18701466}. Apical cell membrane
CC {ECO:0000269|PubMed:24409316}; Multi-pass membrane protein. Basolateral
CC cell membrane {ECO:0000269|PubMed:14739288,
CC ECO:0000269|PubMed:24409316}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:14739288}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=SLC2A9-L {ECO:0000303|PubMed:24409316}, SLC2A9a
CC {ECO:0000303|PubMed:22647630};
CC IsoId=Q9NRM0-1; Sequence=Displayed;
CC Name=2; Synonyms=GLUT9deltaN {ECO:0000303|PubMed:14739288}, SLC2A9-S
CC {ECO:0000303|PubMed:24409316}, SLC2A9b {ECO:0000303|PubMed:22647630};
CC IsoId=Q9NRM0-2; Sequence=VSP_034860;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Most strongly expressed in basolateral
CC membranes of proximal renal tubular cells, liver and placenta. Also
CC detected in lung, blood leukocytes, heart skeletal muscle and
CC chondrocytes from articular cartilage. Detected in kidney membrane (at
CC protein level). {ECO:0000269|PubMed:11991658,
CC ECO:0000269|PubMed:24409316}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Only detected in the apical membranes
CC of polarized renal tubular cells and placenta. Detected in kidney
CC membrane (at protein level). {ECO:0000269|PubMed:24409316}.
CC -!- POLYMORPHISM: Genetic variations in SLC2A9 influence the variance in
CC serum uric acid concentrations and define the serum uric acid
CC concentration quantitative trait locus 2 (UAQTL2) [MIM:612076] with
CC pronounced sex-specific effects. The proportion of the variance of
CC serum uric acid concentrations explained by genotypes is about 1.2% in
CC men and 6% in women, and the percentage accounted for by expression
CC levels is 3.5% in men and 15% in women (PubMed:18327257,
CC PubMed:18327256, PubMed:18842065). Excess serum accumulation of uric
CC acid can lead to the development of gout (PubMed:18327257,
CC PubMed:18327256). {ECO:0000269|PubMed:18327256,
CC ECO:0000269|PubMed:18327257, ECO:0000269|PubMed:18842065}.
CC -!- DISEASE: Hypouricemia renal 2 (RHUC2) [MIM:612076]: A disorder
CC characterized by impaired uric acid reabsorption at the apical membrane
CC of proximal renal tubule cells, and high urinary urate excretion.
CC Patients often appear asymptomatic, but may be subject to exercise-
CC induced acute renal failure, chronic renal dysfunction and
CC nephrolithiasis. {ECO:0000269|PubMed:18701466,
CC ECO:0000269|PubMed:19026395, ECO:0000269|PubMed:19926891,
CC ECO:0000269|PubMed:21810765, ECO:0000269|PubMed:22132964,
CC ECO:0000269|PubMed:22527535, ECO:0000269|PubMed:29967582}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sugar
CC transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: High-capacity urate transporter that was first described as a
CC fructose and glucose transporter. Also described in the literature as
CC high-affinity and low-capacity glucose and fructose transporter
CC (PubMed:18327257, PubMed:17710649, PubMed:18842065). However, another
CC group could not confirm transporter activity for glucose or fructose
CC (PubMed:28083649). {ECO:0000269|PubMed:17710649,
CC ECO:0000269|PubMed:18327257, ECO:0000269|PubMed:18842065,
CC ECO:0000269|PubMed:28083649}.
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DR EMBL; AF210317; AAF85942.1; -; mRNA.
DR EMBL; AC005674; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC098976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108199; AAY41052.1; -; Genomic_DNA.
DR EMBL; BC018897; AAH18897.1; -; mRNA.
DR EMBL; BC110414; AAI10415.1; -; mRNA.
DR EMBL; AF421859; AAL16939.1; -; mRNA.
DR CCDS; CCDS3406.1; -. [Q9NRM0-2]
DR CCDS; CCDS3407.1; -. [Q9NRM0-1]
DR RefSeq; NP_001001290.1; NM_001001290.1. [Q9NRM0-2]
DR RefSeq; NP_064425.2; NM_020041.2. [Q9NRM0-1]
DR AlphaFoldDB; Q9NRM0; -.
DR SMR; Q9NRM0; -.
DR BioGRID; 121156; 64.
DR IntAct; Q9NRM0; 2.
DR STRING; 9606.ENSP00000264784; -.
DR BindingDB; Q9NRM0; -.
DR ChEMBL; CHEMBL2052034; -.
DR DrugBank; DB01914; D-glucose.
DR DrugBank; DB09341; Dextrose, unspecified form.
DR DrugBank; DB09502; Fludeoxyglucose (18F).
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB08844; Uric acid.
DR TCDB; 2.A.1.1.72; the major facilitator superfamily (mfs).
DR GlyGen; Q9NRM0; 1 site.
DR iPTMnet; Q9NRM0; -.
DR PhosphoSitePlus; Q9NRM0; -.
DR BioMuta; SLC2A9; -.
DR DMDM; 300669647; -.
DR EPD; Q9NRM0; -.
DR jPOST; Q9NRM0; -.
DR MassIVE; Q9NRM0; -.
DR PaxDb; Q9NRM0; -.
DR PeptideAtlas; Q9NRM0; -.
DR PRIDE; Q9NRM0; -.
DR ProteomicsDB; 82386; -. [Q9NRM0-1]
DR ProteomicsDB; 82387; -. [Q9NRM0-2]
DR Antibodypedia; 22860; 308 antibodies from 25 providers.
DR DNASU; 56606; -.
DR Ensembl; ENST00000264784.8; ENSP00000264784.3; ENSG00000109667.12. [Q9NRM0-1]
DR Ensembl; ENST00000309065.7; ENSP00000311383.3; ENSG00000109667.12. [Q9NRM0-2]
DR Ensembl; ENST00000506583.5; ENSP00000422209.1; ENSG00000109667.12. [Q9NRM0-2]
DR GeneID; 56606; -.
DR KEGG; hsa:56606; -.
DR MANE-Select; ENST00000264784.8; ENSP00000264784.3; NM_020041.3; NP_064425.2.
DR UCSC; uc003gmc.4; human. [Q9NRM0-1]
DR CTD; 56606; -.
DR DisGeNET; 56606; -.
DR GeneCards; SLC2A9; -.
DR HGNC; HGNC:13446; SLC2A9.
DR HPA; ENSG00000109667; Tissue enhanced (kidney, liver).
DR MalaCards; SLC2A9; -.
DR MIM; 606142; gene.
DR MIM; 612076; phenotype.
DR neXtProt; NX_Q9NRM0; -.
DR OpenTargets; ENSG00000109667; -.
DR Orphanet; 94088; Hereditary renal hypouricemia.
DR PharmGKB; PA37771; -.
DR VEuPathDB; HostDB:ENSG00000109667; -.
DR eggNOG; KOG0569; Eukaryota.
DR GeneTree; ENSGT00940000159192; -.
DR HOGENOM; CLU_001265_30_11_1; -.
DR InParanoid; Q9NRM0; -.
DR OMA; MYQSEST; -.
DR OrthoDB; 326501at2759; -.
DR PhylomeDB; Q9NRM0; -.
DR TreeFam; TF313762; -.
DR PathwayCommons; Q9NRM0; -.
DR Reactome; R-HSA-189200; Cellular hexose transport.
DR Reactome; R-HSA-5619047; Defective SLC2A9 causes hypouricemia renal 2 (RHUC2).
DR SignaLink; Q9NRM0; -.
DR BioGRID-ORCS; 56606; 9 hits in 1072 CRISPR screens.
DR ChiTaRS; SLC2A9; human.
DR GeneWiki; SLC2A9; -.
DR GenomeRNAi; 56606; -.
DR Pharos; Q9NRM0; Tbio.
DR PRO; PR:Q9NRM0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NRM0; protein.
DR Bgee; ENSG00000109667; Expressed in buccal mucosa cell and 125 other tissues.
DR ExpressionAtlas; Q9NRM0; baseline and differential.
DR Genevisible; Q9NRM0; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005351; F:carbohydrate:proton symporter activity; NAS:UniProtKB.
DR GO; GO:0005353; F:fructose transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005355; F:glucose transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015149; F:hexose transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015143; F:urate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015755; P:fructose transmembrane transport; IDA:UniProtKB.
DR GO; GO:1904659; P:glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:0008645; P:hexose transmembrane transport; TAS:Reactome.
DR GO; GO:0015749; P:monosaccharide transmembrane transport; IBA:GO_Central.
DR GO; GO:0046415; P:urate metabolic process; IMP:UniProtKB.
DR GO; GO:0015747; P:urate transport; IDA:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR045263; GLUT.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR003663; Sugar/inositol_transpt.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR PANTHER; PTHR23503; PTHR23503; 1.
DR Pfam; PF00083; Sugar_tr; 1.
DR PRINTS; PR00171; SUGRTRNSPORT.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00879; SP; 1.
DR PROSITE; PS50850; MFS; 1.
DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 1.
DR PROSITE; PS00217; SUGAR_TRANSPORT_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Glycoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..540
FT /note="Solute carrier family 2, facilitated glucose
FT transporter member 9"
FT /id="PRO_0000050378"
FT TOPO_DOM 1..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..107
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..171
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..231
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..337
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..354
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..415
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..451
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..478
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 479..499
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..540
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 519..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..50
FT /note="MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRK
FT -> MKLSKKDRGEDEESDSAKKKL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034860"
FT VARIANT 22
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:18327257"
FT /id="VAR_045648"
FT VARIANT 25
FT /note="G -> R (no effect on urate transport activity;
FT dbSNP:rs2276961)"
FT /evidence="ECO:0000269|PubMed:10860667,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:25268603"
FT /id="VAR_012157"
FT VARIANT 75
FT /note="L -> R (in RHUC2; reduced urate transport activity;
FT decreased protein expression; decreased urate uptake; no
FT effect on glucose transport; dbSNP:rs863225072)"
FT /evidence="ECO:0000269|PubMed:19926891,
FT ECO:0000269|PubMed:29967582"
FT /id="VAR_065772"
FT VARIANT 125
FT /note="T -> M (in RHUC2; markedly reduced urate transport
FT activity; decreased protein expression; decreased urate
FT uptake; no effect on glucose transport; dbSNP:rs181509591)"
FT /evidence="ECO:0000269|PubMed:21810765,
FT ECO:0000269|PubMed:29967582"
FT /id="VAR_065773"
FT VARIANT 169
FT /note="V -> M (no effect on urate transport activity;
FT dbSNP:rs144196049)"
FT /evidence="ECO:0000269|PubMed:25268603"
FT /id="VAR_075343"
FT VARIANT 171
FT /note="R -> C (in RHUC2; unknown pathological significance;
FT according to PubMed:21810765 the variant results in
FT markedly reduced urate uptake, however according to
FT PubMed:29967582 urate transport activity is not affected;
FT no effect on Vmax; no effect on Km for urate; decreased
FT protein expression; no effect on glucose transport;
FT dbSNP:rs776127501)"
FT /evidence="ECO:0000269|PubMed:21810765,
FT ECO:0000269|PubMed:29967582"
FT /id="VAR_065774"
FT VARIANT 191
FT /note="E -> D (in dbSNP:rs376990050)"
FT /evidence="ECO:0000269|PubMed:18327256"
FT /id="VAR_045649"
FT VARIANT 198
FT /note="R -> C (in RHUC2; markedly reduced urate transport
FT activity; decreased Vmax; decreased urate uptake; no effect
FT on protein expression; no effect on glucose transport;
FT dbSNP:rs121908322)"
FT /evidence="ECO:0000269|PubMed:19026395,
FT ECO:0000269|PubMed:22132964, ECO:0000269|PubMed:29967582"
FT /id="VAR_065775"
FT VARIANT 216
FT /note="G -> R (in RHUC2; decreased protein expression;
FT decreased urate uptake; no effect on glucose transport;
FT dbSNP:rs561633150)"
FT /evidence="ECO:0000269|PubMed:18327257,
FT ECO:0000269|PubMed:22527535, ECO:0000269|PubMed:29967582"
FT /id="VAR_045650"
FT VARIANT 275
FT /note="T -> M (no effect on urate transport activity;
FT dbSNP:rs112404957)"
FT /evidence="ECO:0000269|PubMed:18327257,
FT ECO:0000269|PubMed:25268603"
FT /id="VAR_045651"
FT VARIANT 281
FT /note="D -> H (no effect on urate transport activity;
FT dbSNP:rs73225891)"
FT /evidence="ECO:0000269|PubMed:18327256,
FT ECO:0000269|PubMed:18327257, ECO:0000269|PubMed:25268603"
FT /id="VAR_045652"
FT VARIANT 282
FT /note="V -> I (no effect on urate transport activity;
FT dbSNP:rs16890979)"
FT /evidence="ECO:0000269|PubMed:18327256,
FT ECO:0000269|PubMed:22527535, ECO:0000269|PubMed:25268603"
FT /id="VAR_012158"
FT VARIANT 294
FT /note="R -> H (no effect on urate transport activity; no
FT effect on protein expression; no effect on glucose
FT transport; dbSNP:rs3733591)"
FT /evidence="ECO:0000269|PubMed:22527535,
FT ECO:0000269|PubMed:25268603, ECO:0000269|PubMed:29967582"
FT /id="VAR_020337"
FT VARIANT 300
FT /note="R -> H (in dbSNP:rs145688560)"
FT /evidence="ECO:0000269|PubMed:18327257"
FT /id="VAR_045653"
FT VARIANT 333
FT /note="N -> S (in RHUC2; decreased urate uptake; increased
FT Km for urate; no effect on protein expression; no effect on
FT glucose transport)"
FT /evidence="ECO:0000269|PubMed:22527535,
FT ECO:0000269|PubMed:29967582"
FT /id="VAR_086380"
FT VARIANT 350
FT /note="P -> L (no effect on urate transport activity; no
FT effect on urate transport; no effect on protein expression;
FT no effect on glucose; dbSNP:rs2280205)"
FT /evidence="ECO:0000269|PubMed:10860667,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18327256,
FT ECO:0000269|PubMed:22527535, ECO:0000269|PubMed:25268603,
FT ECO:0000269|PubMed:29967582"
FT /id="VAR_012159"
FT VARIANT 380
FT /note="R -> W (in RHUC2; markedly reduced urate transport
FT activity; decreased Vmax; no effect on protein expression;
FT no effect on glucose transport; dbSNP:rs121908321)"
FT /evidence="ECO:0000269|PubMed:19026395,
FT ECO:0000269|PubMed:22132964, ECO:0000269|PubMed:29967582"
FT /id="VAR_065776"
FT VARIANT 412
FT /note="P -> R (in RHUC2; unknown pathological significance;
FT according to PubMed:18701466 the variant results in
FT decreased urate uptake, however according to
FT PubMed:22132964 and PubMed:29967582 urate transport
FT activity is not affected; no effect on Vmax for urate
FT uptake; no effect on affinity for urate; no effect on
FT protein expression; no effect on localization to plasma
FT membrane; no effect on glucose transport)"
FT /evidence="ECO:0000269|PubMed:18701466,
FT ECO:0000269|PubMed:22132964, ECO:0000269|PubMed:29967582"
FT /id="VAR_086381"
FT VARIANT 531
FT /note="V -> I (decreased urate transport; decreased protein
FT expression; no effect on glucose)"
FT /evidence="ECO:0000269|PubMed:29967582"
FT /id="VAR_086382"
FT MUTAGEN 157
FT /note="C->V: No effect on fructose transport. Increased
FT urate binding affinity and decreased urate transport
FT capacity."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 210
FT /note="C->F: Decreased urate uptake. Decreased Vmax for
FT urate transport. Has no effect on glucose transport."
FT /evidence="ECO:0000269|PubMed:29967582"
FT MUTAGEN 210
FT /note="C->T: Decreased fructose transport. Higher affinity
FT and lower transport capacity for urate."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 326
FT /note="C->G: No effect on urate and fructose transport."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 330
FT /note="C->S: Increased fructose transport. Highly reduced
FT urate transport."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 332
FT /note="L->V: Increased fructose binding affinity and
FT decreased fructose transport capacity."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 427
FT /note="C->A: No effect on fructose transport. Higher
FT affinity and lower transport capacity for urate."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 480
FT /note="C->S: No effect on urate and fructose transport."
FT /evidence="ECO:0000269|PubMed:28117388"
FT MUTAGEN 488
FT /note="C->L: No effect on fructose transport. Highly
FT reduced urate transport."
FT /evidence="ECO:0000269|PubMed:28117388"
FT VARIANT Q9NRM0-2:17
FT /note="A -> T (in dbSNP:rs6820230)"
FT /evidence="ECO:0000305"
FT /id="VAR_082920"
SQ SEQUENCE 540 AA; 58702 MW; EEA40123DB5233B4 CRC64;
MARKQNRNSK ELGLVPLTDD TSHAGPPGPG RALLECDHLR SGVPGGRRRK DWSCSLLVAS
LAGAFGSSFL YGYNLSVVNA PTPYIKAFYN ESWERRHGRP IDPDTLTLLW SVTVSIFAIG
GLVGTLIVKM IGKVLGRKHT LLANNGFAIS AALLMACSLQ AGAFEMLIVG RFIMGIDGGV
ALSVLPMYLS EISPKEIRGS LGQVTAIFIC IGVFTGQLLG LPELLGKEST WPYLFGVIVV
PAVVQLLSLP FLPDSPRYLL LEKHNEARAV KAFQTFLGKA DVSQEVEEVL AESRVQRSIR
LVSVLELLRA PYVRWQVVTV IVTMACYQLC GLNAIWFYTN SIFGKAGIPP AKIPYVTLST
GGIETLAAVF SGLVIEHLGR RPLLIGGFGL MGLFFGTLTI TLTLQDHAPW VPYLSIVGIL
AIIASFCSGP GGIPFILTGE FFQQSQRPAA FIIAGTVNWL SNFAVGLLFP FIQKSLDTYC
FLVFATICIT GAIYLYFVLP ETKNRTYAEI SQAFSKRNKA YPPEEKIDSA VTDGKINGRP
