S22AC_HUMAN
ID S22AC_HUMAN Reviewed; 553 AA.
AC Q96S37; B7WPG1; G3XAN7; Q19PF7; Q19PF8; Q19PF9; Q19PG0; Q6UXW3; Q96DT2;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Solute carrier family 22 member 12;
DE AltName: Full=Organic anion transporter 4-like protein;
DE AltName: Full=Renal-specific transporter;
DE Short=RST;
DE AltName: Full=Urate anion exchanger 1;
GN Name=SLC22A12; Synonyms=OATL4, URAT1; ORFNames=UNQ6453/PRO34004;
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), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, VARIANTS RHUC1 MET-217 AND ASP-298, AND
RP CHARACTERIZATION OF VARIANTS RHUC1 MET-217 AND ASP-298.
RC TISSUE=Kidney;
RX PubMed=12024214; DOI=10.1038/nature742;
RA Enomoto A., Kimura H., Chairoungdua A., Shigeta Y., Jutabha P., Cha S.H.,
RA Hosoyamada M., Takeda M., Sekine T., Igarashi T., Matsuo H., Kikuchi Y.,
RA Oda T., Ichida K., Hosoya T., Shimokata K., Niwa T., Kanai Y., Endou H.;
RT "Molecular identification of a renal urate anion exchanger that regulates
RT blood urate levels.";
RL Nature 417:447-452(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rowen L., Madan A., Qin S., Baradarani L., Birditt B., Bloom S., Burke J.,
RA Dors M., Fleetwood P., Kaur A., Madan A., Nesbitt R., Pate D., Hood L.;
RT "Sequencing of human RST gene.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Koyama K.;
RT "Human organic anion transporter 4 similar gene.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 278-318, VARIANT RHUC1 ASP-298, AND
RP VARIANTS GLY-284; CYS-290; GLU-297 AND SER-305.
RX PubMed=16837472; DOI=10.1093/rheumatology/kel205;
RA Vazquez-Mellado J., Jimenez-Vaca A.L., Cuevas-Covarrubias S.,
RA Alvarado-Romano V., Pozo-Molina G., Burgos-Vargas R.;
RT "Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary
RT gout.";
RL Rheumatology 46:215-219(2007).
RN [10]
RP INTERACTION WITH PDZK1.
RX PubMed=14531806; DOI=10.1046/j.1523-1755.2003.00266.x;
RA Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A.,
RA Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H.;
RT "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.";
RL Kidney Int. 64:1733-1745(2003).
RN [11]
RP INTERACTION WITH PDZK1, AND TISSUE SPECIFICITY.
RX PubMed=15304510; DOI=10.1074/jbc.m406724200;
RA Anzai N., Miyazaki H., Noshiro R., Khamdang S., Chairoungdua A., Shin H.J.,
RA Enomoto A., Sakamoto S., Hirata T., Tomita K., Kanai Y., Endou H.;
RT "The multivalent PDZ domain-containing protein PDZK1 regulates transport
RT activity of renal urate-anion exchanger URAT1 via its C terminus.";
RL J. Biol. Chem. 279:45942-45950(2004).
RN [12]
RP VARIANTS RHUC1 HIS-90; MET-138; SER-164; MET-217; LEU-382 AND THR-430, AND
RP CHARACTERIZATION OF VARIANTS RHUC1 HIS-90; MET-138; SER-164; MET-217;
RP LEU-382 AND THR-430.
RX PubMed=14694169; DOI=10.1097/01.asn.0000105320.04395.d0;
RA Ichida K., Hosoyamada M., Hisatome I., Enomoto A., Hikita M., Endou H.,
RA Hosoya T.;
RT "Clinical and molecular analysis of patients with renal hypouricemia in
RT Japan-influence of URAT1 gene on urinary urate excretion.";
RL J. Am. Soc. Nephrol. 15:164-173(2004).
RN [13]
RP VARIANTS RHUC1 HIS-90; 313-ASP--PRO-333 DEL AND HIS-477, VARIANTS VAL-226
RP AND LEU-312, AND CHARACTERIZATION OF VARIANT RHUC1 313-ASP--PRO-333 DEL.
RX PubMed=15327384; DOI=10.1111/j.1523-1755.2004.00839.x;
RA Iwai N., Mino Y., Hosoyamada M., Tago N., Kokubo Y., Endou H.;
RT "A high prevalence of renal hypouricemia caused by inactive SLC22A12 in
RT Japanese.";
RL Kidney Int. 66:935-944(2004).
RN [14]
RP VARIANTS RHUC1 LEU-382 AND ARG-418, AND CHARACTERIZATION OF VARIANTS RHUC1
RP LEU-382 AND ARG-418.
RX PubMed=15634722; DOI=10.1210/jc.2004-1111;
RA Wakida N., Tuyen D.G., Adachi M., Miyoshi T., Nonoguchi H., Oka T.,
RA Ueda O., Tazawa M., Kurihara S., Yoneta Y., Shimada H., Oda T., Kikuchi Y.,
RA Matsuo H., Hosoyamada M., Endou H., Otagiri M., Tomita K., Kitamura K.;
RT "Mutations in human urate transporter 1 gene in presecretory reabsorption
RT defect type of familial renal hypouricemia.";
RL J. Clin. Endocrinol. Metab. 90:2169-2174(2005).
RN [15]
RP VARIANTS RHUC1 HIS-90 AND HIS-477.
RX PubMed=15912381; DOI=10.1007/s00467-005-1863-3;
RA Cheong H.I., Kang J.H., Lee J.H., Ha I.S., Kim S., Komoda F., Sekine T.,
RA Igarashi T., Choi Y.;
RT "Mutational analysis of idiopathic renal hypouricemia in Korea.";
RL Pediatr. Nephrol. 20:886-890(2005).
RN [16]
RP VARIANT CYS-92.
RX PubMed=16385546; DOI=10.1002/art.21499;
RA Graessler J., Graessler A., Unger S., Kopprasch S., Tausche A.-K.,
RA Kuhlisch E., Schroeder H.-E.;
RT "Association of the human urate transporter 1 with reduced renal uric acid
RT excretion and hyperuricemia in a German Caucasian population.";
RL Arthritis Rheum. 54:292-300(2006).
RN [17]
RP VARIANTS RHUC1 THR-75; SER-347; MET-388; CYS-434 AND HIS-434,
RP CHARACTERIZATION OF VARIANTS RHUC1 THR-75; SER-347; MET-388; CYS-434 AND
RP HIS-434, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22194875; DOI=10.1371/journal.pone.0028641;
RA Tasic V., Hynes A.M., Kitamura K., Cheong H.I., Lozanovski V.J., Gucev Z.,
RA Jutabha P., Anzai N., Sayer J.A.;
RT "Clinical and functional characterization of URAT1 variants.";
RL PLoS ONE 6:e28641-e28641(2011).
RN [18]
RP VARIANTS RHUC1 ARG-366 AND HIS-477, AND CHARACTERIZATION OF VARIANT RHUC1
RP ARG-366.
RX PubMed=26418379; DOI=10.1097/maj.0000000000000550;
RA Stiburkova B., Stekrova J., Nakamura M., Ichida K.;
RT "Hereditary renal hypouricemia type 1 and autosomal dominant polycystic
RT kidney disease.";
RL Am. J. Med. Sci. 350:268-271(2015).
CC -!- FUNCTION: Major urate transporter involved in renal reabsorption of
CC urate and helps to maintain blood levels of uric acid (PubMed:12024214,
CC PubMed:22194875). Translocates urate over the apical membrane of
CC proximal tubular cells in exchange for organic anions or chloride ions
CC (PubMed:12024214, PubMed:22194875). {ECO:0000269|PubMed:12024214,
CC ECO:0000269|PubMed:22194875}.
CC -!- SUBUNIT: Interacts with PDZK1. {ECO:0000269|PubMed:14531806,
CC ECO:0000269|PubMed:15304510}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22194875};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000269|PubMed:12024214}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96S37-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96S37-2; Sequence=VSP_028879;
CC Name=3;
CC IsoId=Q96S37-3; Sequence=VSP_054054;
CC Name=4;
CC IsoId=Q96S37-4; Sequence=VSP_054055;
CC -!- TISSUE SPECIFICITY: Detected in kidney (at protein level). Detected in
CC fetal and adult kidney. Detected in epithelial cells of proximal
CC tubules in renal cortex. {ECO:0000269|PubMed:12024214,
CC ECO:0000269|PubMed:15304510}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8CFZ5}.
CC -!- DISEASE: Hypouricemia renal 1 (RHUC1) [MIM:220150]: 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:12024214,
CC ECO:0000269|PubMed:14694169, ECO:0000269|PubMed:15327384,
CC ECO:0000269|PubMed:15634722, ECO:0000269|PubMed:15912381,
CC ECO:0000269|PubMed:16837472, ECO:0000269|PubMed:22194875,
CC ECO:0000269|PubMed:26418379}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB68364.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB071863; BAB96750.1; -; mRNA.
DR EMBL; AC044790; AAK68156.1; -; Genomic_DNA.
DR EMBL; AY358183; AAQ88550.1; -; mRNA.
DR EMBL; AB050269; BAB68364.1; ALT_FRAME; mRNA.
DR EMBL; AK315061; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AP001092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74273.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74274.1; -; Genomic_DNA.
DR EMBL; BC053348; AAH53348.1; -; mRNA.
DR EMBL; DQ514593; ABF74570.1; -; Genomic_DNA.
DR EMBL; DQ514594; ABF74571.1; -; Genomic_DNA.
DR EMBL; DQ514595; ABF74572.1; -; Genomic_DNA.
DR EMBL; DQ514596; ABF74573.1; -; Genomic_DNA.
DR CCDS; CCDS60835.1; -. [Q96S37-4]
DR CCDS; CCDS60836.1; -. [Q96S37-2]
DR CCDS; CCDS8075.1; -. [Q96S37-1]
DR RefSeq; NP_001263255.1; NM_001276326.1. [Q96S37-4]
DR RefSeq; NP_001263256.1; NM_001276327.1. [Q96S37-2]
DR RefSeq; NP_653186.2; NM_144585.3. [Q96S37-1]
DR RefSeq; NP_700357.1; NM_153378.2. [Q96S37-3]
DR AlphaFoldDB; Q96S37; -.
DR SMR; Q96S37; -.
DR BioGRID; 125471; 19.
DR IntAct; Q96S37; 4.
DR MINT; Q96S37; -.
DR STRING; 9606.ENSP00000366797; -.
DR BindingDB; Q96S37; -.
DR ChEMBL; CHEMBL6120; -.
DR DrugBank; DB12466; Favipiravir.
DR DrugBank; DB11560; Lesinurad.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00870; Suprofen.
DR DrugCentral; Q96S37; -.
DR GuidetoPHARMACOLOGY; 1031; -.
DR TCDB; 2.A.1.19.11; the major facilitator superfamily (mfs).
DR GlyGen; Q96S37; 2 sites.
DR PhosphoSitePlus; Q96S37; -.
DR BioMuta; SLC22A12; -.
DR DMDM; 74732700; -.
DR MassIVE; Q96S37; -.
DR PaxDb; Q96S37; -.
DR PeptideAtlas; Q96S37; -.
DR PRIDE; Q96S37; -.
DR ProteomicsDB; 33799; -.
DR ProteomicsDB; 78060; -. [Q96S37-1]
DR ProteomicsDB; 78061; -. [Q96S37-2]
DR Antibodypedia; 15487; 139 antibodies from 24 providers.
DR DNASU; 116085; -.
DR Ensembl; ENST00000336464.7; ENSP00000336836.7; ENSG00000197891.12. [Q96S37-4]
DR Ensembl; ENST00000377567.6; ENSP00000366790.2; ENSG00000197891.12. [Q96S37-2]
DR Ensembl; ENST00000377572.5; ENSP00000366795.1; ENSG00000197891.12. [Q96S37-2]
DR Ensembl; ENST00000377574.6; ENSP00000366797.1; ENSG00000197891.12. [Q96S37-1]
DR Ensembl; ENST00000473690.5; ENSP00000438437.1; ENSG00000197891.12. [Q96S37-3]
DR GeneID; 116085; -.
DR KEGG; hsa:116085; -.
DR MANE-Select; ENST00000377574.6; ENSP00000366797.1; NM_144585.4; NP_653186.2.
DR UCSC; uc001oal.3; human. [Q96S37-1]
DR CTD; 116085; -.
DR DisGeNET; 116085; -.
DR GeneCards; SLC22A12; -.
DR HGNC; HGNC:17989; SLC22A12.
DR HPA; ENSG00000197891; Tissue enriched (kidney).
DR MalaCards; SLC22A12; -.
DR MIM; 220150; phenotype.
DR MIM; 607096; gene.
DR neXtProt; NX_Q96S37; -.
DR OpenTargets; ENSG00000197891; -.
DR Orphanet; 94088; Hereditary renal hypouricemia.
DR PharmGKB; PA38478; -.
DR VEuPathDB; HostDB:ENSG00000197891; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162485; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q96S37; -.
DR OMA; LTWNYLQ; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q96S37; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; Q96S37; -.
DR Reactome; R-HSA-561048; Organic anion transport.
DR Reactome; R-HSA-5619071; Defective SLC22A12 causes renal hypouricemia 1 (RHUC1).
DR SignaLink; Q96S37; -.
DR BioGRID-ORCS; 116085; 15 hits in 1061 CRISPR screens.
DR ChiTaRS; SLC22A12; human.
DR GeneWiki; SLC22A12; -.
DR GenomeRNAi; 116085; -.
DR Pharos; Q96S37; Tclin.
DR PRO; PR:Q96S37; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96S37; protein.
DR Bgee; ENSG00000197891; Expressed in kidney epithelium and 28 other tissues.
DR Genevisible; Q96S37; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0015143; F:urate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0019725; P:cellular homeostasis; NAS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0015711; P:organic anion transport; IBA:GO_Central.
DR GO; GO:0097744; P:renal urate salt excretion; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0046415; P:urate metabolic process; IMP:BHF-UCL.
DR GO; GO:0015747; P:urate transport; IDA:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Glycoprotein;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..553
FT /note="Solute carrier family 22 member 12"
FT /id="PRO_0000307944"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 466..486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 542
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFZ5"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..221
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054054"
FT VAR_SEQ 170..277
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_028879"
FT VAR_SEQ 187..221
FT /note="GTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLL -> V (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054055"
FT VARIANT 65
FT /note="G -> W (in dbSNP:rs12800450)"
FT /id="VAR_036720"
FT VARIANT 75
FT /note="I -> T (in RHUC1; unknown pathological significance;
FT reduced urate transport; decreased localization to cell
FT membrane; dbSNP:rs141570522)"
FT /evidence="ECO:0000269|PubMed:22194875"
FT /id="VAR_084699"
FT VARIANT 90
FT /note="R -> H (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs121907896)"
FT /evidence="ECO:0000269|PubMed:14694169,
FT ECO:0000269|PubMed:15327384, ECO:0000269|PubMed:15912381"
FT /id="VAR_036721"
FT VARIANT 92
FT /note="R -> C (in dbSNP:rs144328876)"
FT /evidence="ECO:0000269|PubMed:16385546"
FT /id="VAR_036722"
FT VARIANT 138
FT /note="V -> M (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs149722479)"
FT /evidence="ECO:0000269|PubMed:14694169"
FT /id="VAR_036723"
FT VARIANT 164
FT /note="G -> S (in RHUC1; reduced urate transport;
FT dbSNP:rs201181059)"
FT /evidence="ECO:0000269|PubMed:14694169"
FT /id="VAR_036724"
FT VARIANT 217
FT /note="T -> M (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs121907893)"
FT /evidence="ECO:0000269|PubMed:12024214,
FT ECO:0000269|PubMed:14694169"
FT /id="VAR_036725"
FT VARIANT 226
FT /note="A -> V (in dbSNP:rs145738825)"
FT /evidence="ECO:0000269|PubMed:15327384"
FT /id="VAR_036726"
FT VARIANT 284
FT /note="R -> G (in some gout patients; uncertain
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:16837472"
FT /id="VAR_036727"
FT VARIANT 290
FT /note="G -> C (in some gout patients; uncertain
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:16837472"
FT /id="VAR_036728"
FT VARIANT 297
FT /note="Q -> E (in some gout patients; uncertain
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:16837472"
FT /id="VAR_036729"
FT VARIANT 298
FT /note="E -> D (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs121907894)"
FT /evidence="ECO:0000269|PubMed:12024214,
FT ECO:0000269|PubMed:16837472"
FT /id="VAR_036730"
FT VARIANT 305
FT /note="I -> S (in some gout patients; uncertain
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:16837472"
FT /id="VAR_036731"
FT VARIANT 312
FT /note="Q -> L"
FT /evidence="ECO:0000269|PubMed:15327384"
FT /id="VAR_036732"
FT VARIANT 313..333
FT /note="Missing (in RHUC1; unknown pathological
FT significance; affects urate transport)"
FT /evidence="ECO:0000269|PubMed:15327384"
FT /id="VAR_036733"
FT VARIANT 347
FT /note="R -> S (in RHUC1; unknown pathological significance;
FT reduced urate transport; no effect on its localization to
FT cell membrane; dbSNP:rs374858585)"
FT /evidence="ECO:0000269|PubMed:22194875"
FT /id="VAR_084700"
FT VARIANT 366
FT /note="G -> R (in RHUC1; reduced urate transport; reduced
FT localization at the plasma membrane; dbSNP:rs1047976958)"
FT /evidence="ECO:0000269|PubMed:26418379"
FT /id="VAR_075344"
FT VARIANT 382
FT /note="Q -> L (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs765990518)"
FT /evidence="ECO:0000269|PubMed:14694169,
FT ECO:0000269|PubMed:15634722"
FT /id="VAR_036734"
FT VARIANT 388
FT /note="V -> M (in RHUC1; unknown pathological significance;
FT no effect on urate transport; no effect on its localization
FT to cell membrane; dbSNP:rs146388519)"
FT /evidence="ECO:0000269|PubMed:22194875"
FT /id="VAR_084701"
FT VARIANT 418
FT /note="L -> R (in RHUC1; strongly reduced urate transport;
FT dbSNP:rs121907895)"
FT /evidence="ECO:0000269|PubMed:15634722"
FT /id="VAR_036735"
FT VARIANT 430
FT /note="M -> T (in RHUC1; reduced urate transport)"
FT /evidence="ECO:0000269|PubMed:14694169"
FT /id="VAR_036736"
FT VARIANT 434
FT /note="R -> C (in RHUC1; unknown pathological significance;
FT strongly reduced urate transport; abolishes localization to
FT cell membrane; dbSNP:rs145200251)"
FT /evidence="ECO:0000269|PubMed:22194875"
FT /id="VAR_084702"
FT VARIANT 434
FT /note="R -> H (in RHUC1; unknown pathological significance;
FT reduced urate transport; abolishes localization to cell
FT membrane; dbSNP:rs147647315)"
FT /evidence="ECO:0000269|PubMed:22194875"
FT /id="VAR_084703"
FT VARIANT 477
FT /note="R -> H (in RHUC1; dbSNP:rs773677616)"
FT /evidence="ECO:0000269|PubMed:15327384,
FT ECO:0000269|PubMed:15912381, ECO:0000269|PubMed:26418379"
FT /id="VAR_036737"
FT CONFLICT 451
FT /note="C -> Y (in Ref. 3; AAQ88550)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="A -> T (in Ref. 5; AK315061)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 59630 MW; E3F29F38129BAD61 CRC64;
MAFSELLDLV GGLGRFQVLQ TMALMVSIMW LCTQSMLENF SAAVPSHRCW APLLDNSTAQ
ASILGSLSPE ALLAISIPPG PNQRPHQCRR FRQPQWQLLD PNATATSWSE ADTEPCVDGW
VYDRSIFTST IVAKWNLVCD SHALKPMAQS IYLAGILVGA AACGPASDRF GRRLVLTWSY
LQMAVMGTAA AFAPAFPVYC LFRFLLAFAV AGVMMNTGTL LMEWTAARAR PLVMTLNSLG
FSFGHGLTAA VAYGVRDWTL LQLVVSVPFF LCFLYSWWLA ESARWLLTTG RLDWGLQELW
RVAAINGKGA VQDTLTPEVL LSAMREELSM GQPPASLGTL LRMPGLRFRT CISTLCWFAF
GFTFFGLALD LQALGSNIFL LQMFIGVVDI PAKMGALLLL SHLGRRPTLA ASLLLAGLCI
LANTLVPHEM GALRSALAVL GLGGVGAAFT CITIYSSELF PTVLRMTAVG LGQMAARGGA
ILGPLVRLLG VHGPWLPLLV YGTVPVLSGL AALLLPETQS LPLPDTIQDV QNQAVKKATH
GTLGNSVLKS TQF
