Q9NRM0 (GTR9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 2, facilitated glucose transporter member 9

Alternative name(s):
Glucose transporter type 9
Short name=GLUT-9

Gene names

Name:	SLC2A9
Synonyms:	GLUT9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	540 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transport urate and fructose. May have a role in the urate reabsorption by proximal tubules. Also transports glucose at low rate. Ref.5 Ref.7
Subcellular location	Membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Most strongly expressed in basolateral membranes of proximal renal tubular cells, liver and placenta. Also detected in lung, blood leukocytes, heart skeletal muscle and chondrocytes from articular cartilage. Isoform 2 is only detected in the apical membranes of polarized renal tubular cells and placenta. Isoform 1 and isoform 2 are detected in kidney membrane (at protein level). Ref.4 Ref.5
Polymorphism	Genetic variations in SLC2A9 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 2 (UAQTL2) [MIM:612076]. Excess serum accumulation of uric acid can lead to the development of gout.
Involvement in disease	Hypouricemia renal 2 (RHUC2) [MIM:612076]: A disorder characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells, and high urinary urate excretion. Patients often appear asymptomatic, but may be subject to exercise-induced acute renal failure, chronic renal dysfunction and nephrolithiasis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Ref.11
Sequence similarities	Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily. [View classification]

Ontologies

Keywords
Biological process	Sugar transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose transport Non-traceable author statement Ref.1. Source: UniProtKB urate metabolic process Inferred from mutant phenotype PubMed 18834626PubMed 20053405. Source: UniProtKB
Cellular_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB integral to plasma membrane Inferred from electronic annotation. Source: Compara nuclear envelope Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	glucose transmembrane transporter activity Inferred from electronic annotation. Source: Compara sugar:hydrogen symporter activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NRM0-1)

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: Q9NRM0-2)

Also known as: GLUT9deltaN;

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRK → MKLSKKDRGEDEESDSAKKKL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 540	540	Solute carrier family 2, facilitated glucose transporter member 9		PRO_0000050378
Regions
	Topological domain	1 – 51	51	Cytoplasmic Potential
	Transmembrane	52 – 72	21	Helical; Name=1; Potential
	Topological domain	73 – 107	35	Extracellular Potential
	Transmembrane	108 – 128	21	Helical; Name=2; Potential
	Topological domain	129 – 140	12	Cytoplasmic Potential
	Transmembrane	141 – 161	21	Helical; Name=3; Potential
	Topological domain	162 – 171	10	Extracellular Potential
	Transmembrane	172 – 192	21	Helical; Name=4; Potential
	Topological domain	193 – 200	8	Cytoplasmic Potential
	Transmembrane	201 – 221	21	Helical; Name=5; Potential
	Topological domain	222 – 231	10	Extracellular Potential
	Transmembrane	232 – 252	21	Helical; Name=6; Potential
	Topological domain	253 – 316	64	Cytoplasmic Potential
	Transmembrane	317 – 337	21	Helical; Name=7; Potential
	Topological domain	338 – 354	17	Extracellular Potential
	Transmembrane	355 – 375	21	Helical; Name=8; Potential
	Topological domain	376 – 381	6	Cytoplasmic Potential
	Transmembrane	382 – 402	21	Helical; Name=9; Potential
	Topological domain	403 – 415	13	Extracellular Potential
	Transmembrane	416 – 436	21	Helical; Name=10; Potential
	Topological domain	437 – 451	15	Cytoplasmic Potential
	Transmembrane	452 – 472	21	Helical; Name=11; Potential
	Topological domain	473 – 478	6	Extracellular Potential
	Transmembrane	479 – 499	21	Helical; Name=12; Potential
	Topological domain	500 – 540	41	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	90	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 50	50	MARKQ…GRRRK → MKLSKKDRGEDEESDSAKKK L in isoform 2.		VSP_034860
	Natural variant	22	1	S → N. Ref.7		VAR_045648
	Natural variant	25	1	G → R. Ref.1 Ref.3 Corresponds to variant rs2276961 [ dbSNP | Ensembl ].		VAR_012157
	Natural variant	75	1	L → R in RHUC2; reduced urate transport activity. Ref.10		VAR_065772
	Natural variant	125	1	T → M in RHUC2; markedly reduced urate transport activity. Ref.11		VAR_065773
	Natural variant	171	1	R → C in RHUC2; markedly reduced urate transport activity. Ref.11		VAR_065774
	Natural variant	191	1	E → D. Ref.6		VAR_045649
	Natural variant	198	1	R → C in RHUC2; markedly reduced urate transport activity. Ref.8		VAR_065775
	Natural variant	216	1	G → R. Ref.7		VAR_045650
	Natural variant	275	1	T → M. Ref.7		VAR_045651
	Natural variant	281	1	D → H. Ref.6 Ref.7		VAR_045652
	Natural variant	282	1	V → I. Ref.6 Corresponds to variant rs16890979 [ dbSNP | Ensembl ].		VAR_012158
	Natural variant	294	1	R → H. Corresponds to variant rs3733591 [ dbSNP | Ensembl ].		VAR_020337
	Natural variant	300	1	R → H. Ref.7		VAR_045653
	Natural variant	350	1	P → L. Ref.1 Ref.3 Ref.6 Corresponds to variant rs2280205 [ dbSNP | Ensembl ].		VAR_012159
	Natural variant	380	1	R → W in RHUC2; markedly reduced urate transport activity. Ref.8		VAR_065776
Isoform 2:
	Natural variant	17	1	A → T in dbSNP:6820230.

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 13, 2010. Version 2. Checksum: EEA40123DB5233B4	FASTA	540	58,702
	10 20 30 40 50 60 MARKQNRNSK ELGLVPLTDD TSHAGPPGPG RALLECDHLR SGVPGGRRRK DWSCSLLVAS 70 80 90 100 110 120 LAGAFGSSFL YGYNLSVVNA PTPYIKAFYN ESWERRHGRP IDPDTLTLLW SVTVSIFAIG 130 140 150 160 170 180 GLVGTLIVKM IGKVLGRKHT LLANNGFAIS AALLMACSLQ AGAFEMLIVG RFIMGIDGGV 190 200 210 220 230 240 ALSVLPMYLS EISPKEIRGS LGQVTAIFIC IGVFTGQLLG LPELLGKEST WPYLFGVIVV 250 260 270 280 290 300 PAVVQLLSLP FLPDSPRYLL LEKHNEARAV KAFQTFLGKA DVSQEVEEVL AESRVQRSIR 310 320 330 340 350 360 LVSVLELLRA PYVRWQVVTV IVTMACYQLC GLNAIWFYTN SIFGKAGIPP AKIPYVTLST 370 380 390 400 410 420 GGIETLAAVF SGLVIEHLGR RPLLIGGFGL MGLFFGTLTI TLTLQDHAPW VPYLSIVGIL 430 440 450 460 470 480 AIIASFCSGP GGIPFILTGE FFQQSQRPAA FIIAGTVNWL SNFAVGLLFP FIQKSLDTYC 490 500 510 520 530 540 FLVFATICIT GAIYLYFVLP ETKNRTYAEI SQAFSKRNKA YPPEEKIDSA VTDGKINGRP
	Isoform 2 (GLUT9deltaN) [UniParc]. Checksum: CF8BD02FCBB0BC42	FASTA	511	55,721
	10 20 30 40 50 60 MKLSKKDRGE DEESDSAKKK LDWSCSLLVA SLAGAFGSSF LYGYNLSVVN APTPYIKAFY 70 80 90 100 110 120 NESWERRHGR PIDPDTLTLL WSVTVSIFAI GGLVGTLIVK MIGKVLGRKH TLLANNGFAI 130 140 150 160 170 180 SAALLMACSL QAGAFEMLIV GRFIMGIDGG VALSVLPMYL SEISPKEIRG SLGQVTAIFI 190 200 210 220 230 240 CIGVFTGQLL GLPELLGKES TWPYLFGVIV VPAVVQLLSL PFLPDSPRYL LLEKHNEARA 250 260 270 280 290 300 VKAFQTFLGK ADVSQEVEEV LAESRVQRSI RLVSVLELLR APYVRWQVVT VIVTMACYQL 310 320 330 340 350 360 CGLNAIWFYT NSIFGKAGIP PAKIPYVTLS TGGIETLAAV FSGLVIEHLG RRPLLIGGFG 370 380 390 400 410 420 LMGLFFGTLT ITLTLQDHAP WVPYLSIVGI LAIIASFCSG PGGIPFILTG EFFQQSQRPA 430 440 450 460 470 480 AFIIAGTVNW LSNFAVGLLF PFIQKSLDTY CFLVFATICI TGAIYLYFVL PETKNRTYAE 490 500 510 ISQAFSKRNK AYPPEEKIDS AVTDGKINGR P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9 (GLUT9)." Phay J.E., Hussain H.B., Moley J.F. Genomics 66:217-220(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-25 AND LEU-350. Tissue: Kidney.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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 2), VARIANTS ARG-25 AND LEU-350. Tissue: Lung and Ovary.
[4]	"Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9." Mobasheri A., Neama G., Bell S., Richardson S., Carter S.D. Cell Biol. Int. 26:297-300(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-238 (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Articular cartilage.
[5]	"Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking." Augustin R., Carayannopoulos M.O., Dowd L.O., Phay J.E., Moley J.F., Moley K.H. J. Biol. Chem. 279:16229-16236(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
[6]	"SLC2A9 influences uric acid concentrations with pronounced sex-specific effects." Doering A., Gieger C., Mehta D., Gohlke H., Prokisch H., Coassin S., Fischer G., Henke K., Klopp N., Kronenberg F., Paulweber B., Pfeufer A., Rosskopf D., Voelzke H., Illig T., Meitinger T., Wichmann H.-E., Meisinger C. Nat. Genet. 40:430-436(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN THE REGULATION OF SERUM URIC ACID CONCENTRATION, VARIANTS ASP-191; HIS-281; ILE-282 AND LEU-350.
[7]	"SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout." Vitart V., Rudan I., Hayward C., Gray N.K., Floyd J., Palmer C.N., Knott S.A., Kolcic I., Polasek O., Graessler J., Wilson J.F., Marinaki A., Riches P.L., Shu X., Janicijevic B., Smolej-Narancic N., Gorgoni B., Morgan J. , Campbell S., Biloglav Z., Barac-Lauc L., Pericic M., Klaric I.M., Zgaga L., Skaric-Juric T., Wild S.H., Richardson W.A., Hohenstein P., Kimber C.H., Tenesa A., Donnelly L.A., Fairbanks L.D., Aringer M., McKeigue P.M., Ralston S.H., Morris A.D., Rudan P., Hastie N.D., Campbell H., Wright A.F. Nat. Genet. 40:437-442(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN THE REGULATION OF SERUM URIC ACID CONCENTRATION, FUNCTION, VARIANTS ASN-22; ARG-216; MET-275; HIS-281 AND HIS-300.
[8]	"Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia." Matsuo H., Chiba T., Nagamori S., Nakayama A., Domoto H., Phetdee K., Wiriyasermkul P., Kikuchi Y., Oda T., Nishiyama J., Nakamura T., Morimoto Y., Kamakura K., Sakurai Y., Nonoyama S., Kanai Y., Shinomiya N. Am. J. Hum. Genet. 83:744-751(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC2 CYS-198 AND TRP-380, CHARACTERIZATION OF VARIANTS RHUC2 CYS-198 AND TRP-380.
[9]	Erratum Matsuo H., Chiba T., Nagamori S., Nakayama A., Domoto H., Phetdee K., Wiriyasermkul P., Kikuchi Y., Oda T., Nishiyama J., Nakamura T., Morimoto Y., Kamakura K., Sakurai Y., Nonoyama S., Kanai Y., Shinomiya N. Am. J. Hum. Genet. 83:795-795(2008)
[10]	"Homozygous SLC2A9 mutations cause severe renal hypouricemia." Dinour D., Gray N.K., Campbell S., Shu X., Sawyer L., Richardson W., Rechavi G., Amariglio N., Ganon L., Sela B.A., Bahat H., Goldman M., Weissgarten J., Millar M.R., Wright A.F., Holtzman E.J. J. Am. Soc. Nephrol. 21:64-72(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RHUC2 ARG-75, CHARACTERIZATION OF VARIANT RHUC2 ARG-75.
[11]	"Two novel homozygous SLC2A9 mutations cause renal hypouricemia type 2." Dinour D., Gray N.K., Ganon L., Knox A.J., Shalev H., Sela B.A., Campbell S., Sawyer L., Shu X., Valsamidou E., Landau D., Wright A.F., Holtzman E.J. Nephrol. Dial. Transplant. 27:1035-1041(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC2 MET-125 AND CYS-171, CHARACTERIZATION OF VARIANTS RHUC2 MET-125 AND CYS-171.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF210317 mRNA. Translation: AAF85942.1. AC005674 Genomic DNA. No translation available. AC098976 Genomic DNA. No translation available. AC108199 Genomic DNA. Translation: AAY41052.1. BC018897 mRNA. Translation: AAH18897.1. BC110414 mRNA. Translation: AAI10415.1. AF421859 mRNA. Translation: AAL16939.1.
IPI	IPI00024031. IPI00163506.
RefSeq	NP_001001290.1. NM_001001290.1. NP_064425.2. NM_020041.2.
UniGene	Hs.656895.
3D structure databases
ProteinModelPortal	Q9NRM0.
SMR	Q9NRM0. Positions 161-510.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000264784.
Protein family/group databases
TCDB	2.A.1.1.72. major facilitator superfamily (MFS).
PTM databases
PhosphoSite	Q9NRM0.
Polymorphism databases
DMDM	300669647.
Proteomic databases
PaxDb	Q9NRM0.
PRIDE	Q9NRM0.
Protocols and materials databases
DNASU	56606.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264784; ENSP00000264784; ENSG00000109667. ENST00000309065; ENSP00000311383; ENSG00000109667. ENST00000506583; ENSP00000422209; ENSG00000109667.
GeneID	56606.
KEGG	hsa:56606.
UCSC	uc003gmc.3. human. uc003gmd.3. human.
Organism-specific databases
CTD	56606.
GeneCards	GC04M009772.
H-InvDB	HIX0004090.
HGNC	HGNC:13446. SLC2A9.
MIM	606142. gene. 612076. phenotype.
neXtProt	NX_Q9NRM0.
Orphanet	94088. Hereditary renal hypouricemia.
PharmGKB	PA37771.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOGENOM	HOG000202871.
HOVERGEN	HBG014816.
InParanoid	Q9NRM0.
KO	K08146.
OMA	VKAFQTF.
PhylomeDB	Q9NRM0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9NRM0.
Bgee	Q9NRM0.
CleanEx	HS_SLC2A9.
Genevestigator	Q9NRM0.
GermOnline	ENSG00000109667. Homo sapiens.
Family and domain databases
InterPro	IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR005828. Sub_transporter. IPR003663. Sugar/inositol_transpt. IPR005829. Sugar_transporter_CS. [Graphical view]
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
PRINTS	PR00171. SUGRTRNSPORT.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00879. SP. 1 hit.
PROSITE	PS50850. MFS. 1 hit. PS00216. SUGAR_TRANSPORT_1. 1 hit. PS00217. SUGAR_TRANSPORT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	56606.
NextBio	62053.
SOURCE	Search...

Entry information

Entry name

GTR9_HUMAN

Accession

Primary (citable) accession number: Q9NRM0
Secondary accession number(s): Q0VGC4 , Q4W5D1, Q8WV30, Q96P00

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	July 13, 2010
Last modified:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.