Q96S37 (S22AC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 22 member 12

Alternative name(s):
Organic anion transporter 4-like protein
Renal-specific transporter
Short name=RST
Urate anion exchanger 1

Gene names

Name:	SLC22A12
Synonyms:	OATL4, URAT1
ORF Names:	UNQ6453/PRO34004

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	553 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for efficient urate re-absorption in the kidney. Regulates blood urate levels. Mediates saturable urate uptake by facilitating the exchange of urate against organic anions. Ref.1
Subunit structure	Interacts with PDZK1. Ref.9 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Detected in the luminal membrane of the epithelium of renal proximal tubules. Ref.1
Tissue specificity	Detected in kidney (at protein level). Detected in fetal and adult kidney. Detected in epithelial cells of proximal tubules in renal cortex. Ref.1 Ref.10
Involvement in disease	Hypouricemia renal 1 (RHUC1) [MIM:220150]: 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.1 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]
Sequence caution	The sequence BAB68364.1 differs from that shown. Reason: Frameshift at positions 84 and 136.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane 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	cellular homeostasis Non-traceable author statement PubMed 15772301. Source: UniProtKB response to drug Inferred from direct assay Ref.1. Source: UniProtKB urate metabolic process Inferred from mutant phenotype PubMed 19503597. Source: BHF-UCL urate transport Inferred from direct assay Ref.1PubMed 16775029. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB brush border membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	urate transmembrane transporter activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96S37-1)

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: Q96S37-2)

The sequence of this isoform differs from the canonical sequence as follows:
     170-277: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 553	553	Solute carrier family 22 member 12		PRO_0000307944
Regions
	Transmembrane	9 – 29	21	Helical; Potential
	Transmembrane	146 – 166	21	Helical; Potential
	Transmembrane	174 – 194	21	Helical; Potential
	Transmembrane	195 – 215	21	Helical; Potential
	Transmembrane	232 – 252	21	Helical; Potential
	Transmembrane	260 – 280	21	Helical; Potential
	Transmembrane	351 – 371	21	Helical; Potential
	Transmembrane	378 – 398	21	Helical; Potential
	Transmembrane	407 – 427	21	Helical; Potential
	Transmembrane	435 – 455	21	Helical; Potential
	Transmembrane	466 – 486	21	Helical; Potential
	Transmembrane	495 – 515	21	Helical; Potential
Amino acid modifications
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	170 – 277	108	Missing in isoform 2.		VSP_028879
	Natural variant	65	1	G → W. Corresponds to variant rs12800450 [ dbSNP | Ensembl ].		VAR_036720
	Natural variant	90	1	R → H in RHUC1; strongly reduced urate transport. Ref.11 Ref.12 Ref.14		VAR_036721
	Natural variant	92	1	R → C. Ref.15		VAR_036722
	Natural variant	138	1	V → M in RHUC1; strongly reduced urate transport. Ref.11		VAR_036723
	Natural variant	164	1	G → S in RHUC1; reduced urate transport. Ref.11		VAR_036724
	Natural variant	217	1	T → M in RHUC1; strongly reduced urate transport. Ref.1 Ref.11		VAR_036725
	Natural variant	226	1	A → V. Ref.12		VAR_036726
	Natural variant	284	1	R → G in some gout patients; uncertain pathological significance. Ref.8		VAR_036727
	Natural variant	290	1	G → C in some gout patients; uncertain pathological significance. Ref.8		VAR_036728
	Natural variant	297	1	Q → E in some gout patients; uncertain pathological significance. Ref.8		VAR_036729
	Natural variant	298	1	E → D in RHUC1; strongly reduced urate transport. Ref.1 Ref.8		VAR_036730
	Natural variant	305	1	I → S in some gout patients; uncertain pathological significance. Ref.8		VAR_036731
	Natural variant	312	1	Q → L. Ref.12		VAR_036732
	Natural variant	313 – 333	21	Missing Affects urate transport.		VAR_036733
	Natural variant	382	1	Q → L in RHUC1; strongly reduced urate transport. Ref.11 Ref.13		VAR_036734
	Natural variant	418	1	L → R in RHUC1; strongly reduced urate transport. Ref.13		VAR_036735
	Natural variant	430	1	M → T in RHUC1; reduced urate transport. Ref.11		VAR_036736
	Natural variant	477	1	R → H in RHUC1. Ref.12 Ref.14		VAR_036737
Experimental info
	Sequence conflict	451	1	C → Y in AAQ88550. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: E3F29F38129BAD61	FASTA	553	59,630
	10 20 30 40 50 60 MAFSELLDLV GGLGRFQVLQ TMALMVSIMW LCTQSMLENF SAAVPSHRCW APLLDNSTAQ 70 80 90 100 110 120 ASILGSLSPE ALLAISIPPG PNQRPHQCRR FRQPQWQLLD PNATATSWSE ADTEPCVDGW 130 140 150 160 170 180 VYDRSIFTST IVAKWNLVCD SHALKPMAQS IYLAGILVGA AACGPASDRF GRRLVLTWSY 190 200 210 220 230 240 LQMAVMGTAA AFAPAFPVYC LFRFLLAFAV AGVMMNTGTL LMEWTAARAR PLVMTLNSLG 250 260 270 280 290 300 FSFGHGLTAA VAYGVRDWTL LQLVVSVPFF LCFLYSWWLA ESARWLLTTG RLDWGLQELW 310 320 330 340 350 360 RVAAINGKGA VQDTLTPEVL LSAMREELSM GQPPASLGTL LRMPGLRFRT CISTLCWFAF 370 380 390 400 410 420 GFTFFGLALD LQALGSNIFL LQMFIGVVDI PAKMGALLLL SHLGRRPTLA ASLLLAGLCI 430 440 450 460 470 480 LANTLVPHEM GALRSALAVL GLGGVGAAFT CITIYSSELF PTVLRMTAVG LGQMAARGGA 490 500 510 520 530 540 ILGPLVRLLG VHGPWLPLLV YGTVPVLSGL AALLLPETQS LPLPDTIQDV QNQAVKKATH 550 GTLGNSVLKS TQF
	Isoform 2 [UniParc]. Checksum: 5385EA4A75ABD7C4	FASTA	445	47,648
	10 20 30 40 50 60 MAFSELLDLV GGLGRFQVLQ TMALMVSIMW LCTQSMLENF SAAVPSHRCW APLLDNSTAQ 70 80 90 100 110 120 ASILGSLSPE ALLAISIPPG PNQRPHQCRR FRQPQWQLLD PNATATSWSE ADTEPCVDGW 130 140 150 160 170 180 VYDRSIFTST IVAKWNLVCD SHALKPMAQS IYLAGILVGA AACGPASDRW LAESARWLLT 190 200 210 220 230 240 TGRLDWGLQE LWRVAAINGK GAVQDTLTPE VLLSAMREEL SMGQPPASLG TLLRMPGLRF 250 260 270 280 290 300 RTCISTLCWF AFGFTFFGLA LDLQALGSNI FLLQMFIGVV DIPAKMGALL LLSHLGRRPT 310 320 330 340 350 360 LAASLLLAGL CILANTLVPH EMGALRSALA VLGLGGVGAA FTCITIYSSE LFPTVLRMTA 370 380 390 400 410 420 VGLGQMAARG GAILGPLVRL LGVHGPWLPL LVYGTVPVLS GLAALLLPET QSLPLPDTIQ 430 440 DVQNQAVKKA THGTLGNSVL KSTQF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular identification of a renal urate anion exchanger that regulates blood urate levels." Enomoto A., Kimura H., Chairoungdua A., Shigeta Y., Jutabha P., Cha S.H., Hosoyamada M., Takeda M., Sekine T., Igarashi T., Matsuo H., Kikuchi Y., Oda T., Ichida K., Hosoya T., Shimokata K., Niwa T., Kanai Y., Endou H. Nature 417:447-452(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANTS RHUC1 MET-217 AND ASP-298, CHARACTERIZATION OF VARIANTS RHUC1 MET-217 AND ASP-298. Tissue: Kidney.
[2]	"Sequencing of human RST gene." Rowen L., Madan A., Qin S., Baradarani L., Birditt B., Bloom S., Burke J., Dors M., Fleetwood P., Kaur A., Madan A., Nesbitt R., Pate D., Hood L. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Human organic anion transporter 4 similar gene." Koyama K. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney.
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Colon.
[8]	"Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout." Vazquez-Mellado J., Jimenez-Vaca A.L., Cuevas-Covarrubias S., Alvarado-Romano V., Pozo-Molina G., Burgos-Vargas R. Rheumatology 46:215-219(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 278-318, VARIANT RHUC1 ASP-298, VARIANTS GLY-284; CYS-290; GLU-297 AND SER-305.
[9]	"PDZK1: I. a major scaffolder in brush borders of proximal tubular cells." Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A., Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H. Kidney Int. 64:1733-1745(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDZK1.
[10]	"The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus." Anzai N., Miyazaki H., Noshiro R., Khamdang S., Chairoungdua A., Shin H.J., Enomoto A., Sakamoto S., Hirata T., Tomita K., Kanai Y., Endou H. J. Biol. Chem. 279:45942-45950(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDZK1, TISSUE SPECIFICITY.
[11]	"Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion." Ichida K., Hosoyamada M., Hisatome I., Enomoto A., Hikita M., Endou H., Hosoya T. J. Am. Soc. Nephrol. 15:164-173(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC1 HIS-90; MET-138; SER-164; MET-217; LEU-382 AND THR-430, CHARACTERIZATION OF VARIANTS RHUC1 HIS-90; MET-138; SER-164; MET-217; LEU-382 AND THR-430.
[12]	"A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese." Iwai N., Mino Y., Hosoyamada M., Tago N., Kokubo Y., Endou H. Kidney Int. 66:935-944(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC1 HIS-90 AND HIS-477, VARIANTS VAL-226; LEU-312 AND 313-ASP--PRO-333 DEL, CHARACTERIZATION OF VARIANT 313-ASP--PRO-333 DEL.
[13]	"Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia." Wakida N., Tuyen D.G., Adachi M., Miyoshi T., Nonoguchi H., Oka T., Ueda O., Tazawa M., Kurihara S., Yoneta Y., Shimada H., Oda T., Kikuchi Y., Matsuo H., Hosoyamada M., Endou H., Otagiri M., Tomita K., Kitamura K. J. Clin. Endocrinol. Metab. 90:2169-2174(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC1 LEU-382 AND ARG-418, CHARACTERIZATION OF VARIANTS RHUC1 LEU-382 AND ARG-418.
[14]	"Mutational analysis of idiopathic renal hypouricemia in Korea." Cheong H.I., Kang J.H., Lee J.H., Ha I.S., Kim S., Komoda F., Sekine T., Igarashi T., Choi Y. Pediatr. Nephrol. 20:886-890(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHUC1 HIS-90 AND HIS-477.
[15]	"Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population." Graessler J., Graessler A., Unger S., Kopprasch S., Tausche A.-K., Kuhlisch E., Schroeder H.-E. Arthritis Rheum. 54:292-300(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-92.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB071863 mRNA. Translation: BAB96750.1. AC044790 Genomic DNA. Translation: AAK68156.1. AY358183 mRNA. Translation: AAQ88550.1. AB050269 mRNA. Translation: BAB68364.1. Frameshift. AP001092 Genomic DNA. No translation available. CH471076 Genomic DNA. Translation: EAW74273.1. BC053348 mRNA. Translation: AAH53348.1. DQ514593 Genomic DNA. Translation: ABF74570.1. DQ514594 Genomic DNA. Translation: ABF74571.1. DQ514595 Genomic DNA. Translation: ABF74572.1. DQ514596 Genomic DNA. Translation: ABF74573.1.
IPI	IPI00163325. IPI00432750.
RefSeq	NP_001263256.1. NM_001276327.1. NP_653186.2. NM_144585.3.
UniGene	Hs.174424.
3D structure databases
ProteinModelPortal	Q96S37.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000366797.
Protein family/group databases
TCDB	2.A.1.19.11. major facilitator superfamily (MFS).
PTM databases
PhosphoSite	Q96S37.
Polymorphism databases
DMDM	74732700.
Proteomic databases
PaxDb	Q96S37.
PRIDE	Q96S37.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377567; ENSP00000366790; ENSG00000197891. ENST00000377572; ENSP00000366795; ENSG00000197891. ENST00000377574; ENSP00000366797; ENSG00000197891.
GeneID	116085.
KEGG	hsa:116085.
UCSC	uc001oal.1. human. uc001oan.1. human.
Organism-specific databases
CTD	116085.
GeneCards	GC11P064359.
HGNC	HGNC:17989. SLC22A12.
HPA	HPA024575.
MIM	220150. phenotype. 607096. gene.
neXtProt	NX_Q96S37.
Orphanet	94088. Hereditary renal hypouricemia.
PharmGKB	PA38478.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238692.
HOVERGEN	HBG108433.
InParanoid	Q96S37.
KO	K08208.
OMA	STLCWFA.
OrthoDB	EOG418BPG.
PhylomeDB	Q96S37.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q96S37.
Bgee	Q96S37.
CleanEx	HS_SLC22A12.
Genevestigator	Q96S37.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q96S37.
ChEMBL	CHEMBL6120.
ChiTaRS	SLC22A12. human.
GenomeRNAi	116085.
NextBio	79751.
SOURCE	Search...

Entry information

Entry name

S22AC_HUMAN

Accession

Primary (citable) accession number: Q96S37
Secondary accession number(s): B7WPG1 , Q19PF7, Q19PF8, Q19PF9, Q19PG0, Q6UXW3, Q96DT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 2007
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 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.