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2.A.1.19.11
The apical proximal tubular renal urate:anion exchanger, URAT1 (Slc22a12).  Catalyzes Na+-independent anion efflux (secretion) and reabsorption (Eraly et al., 2003a,b; Anzai and Endou, 2011; Prestin et al. 2014)  Regulated by the PDZK1 protein; Anzai et al., 2004). Also transports orotate, a precursor of pyrimidine biosynthesis (Miura et al., 2011). Mutations in URAT1 cause hereditary renal hypouricemia/gaut.  Residues involved in urea and inhibitor binding have been identified (Tan et al. 2016). Mutations can cause renal hypouricemia (RHUC), a heterogeneous genetic disorder that is characterized by decreased serum uric acid concentrations and increased fractional excretion of uric acid (Zhou et al. 2018; Kaynar et al. 2022). Mutation in transmembrane domain 8 of the human urate transporter 1 (residue K393) disrupts uric acid recognition and transport (Lan et al. 2022). Pathogenic variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) can give rise to renal hypouricemia (Perdomo-Ramirez et al. 2023). Biphenyl carboxylic acid derivatives are potent URAT1 inhibitors (Hou et al. 2023).

Accession Number:Q96S37
Protein Name:URAT1 aka RST aka SLC22A12
Length:553
Molecular Weight:59630.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate anion, 7,9-dihydro-1H-purine-2,6,8(3H)-trione, orotate

Cross database links:

RefSeq: NP_653186.2    NP_700357.1   
Entrez Gene ID: 116085   
Pfam: PF07690   
OMIM: 220150  phenotype
607096  gene
KEGG: hsa:116085    hsa:116085   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0031526 C:brush border membrane
GO:0016021 C:integral to membrane
GO:0030165 F:PDZ domain binding
GO:0015143 F:urate transmembrane transporter activity
GO:0019725 P:cellular homeostasis
GO:0042493 P:response to drug
GO:0055085 P:transmembrane transport
GO:0015747 P:urate transport
GO:0046415 P:urate metabolic process

References (24)

[1] “Molecular identification of a renal urate anion exchanger that regulates blood urate levels.”  Enomoto A.et.al.   12024214
[2] “The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.”  Clark H.F.et.al.   12975309
[3] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.”  Vazquez-Mellado J.et.al.   16837472
[6] “PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.”  Gisler S.M.et.al.   14531806
[7] “The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.”  Anzai N.et.al.   15304510
[8] “Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.”  Ichida K.et.al.   14694169
[9] “A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese.”  Iwai N.et.al.   15327384
[10] “Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.”  Wakida N.et.al.   15634722
[11] “Mutational analysis of idiopathic renal hypouricemia in Korea.”  Cheong H.I.et.al.   15912381
[12] “Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.”  Graessler J.et.al.   16385546
[13] “Molecular identification of a renal urate anion exchanger that regulates blood urate levels.”  Enomoto A.et.al.   12024214
[14] “The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.”  Clark H.F.et.al.   12975309
[15] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[16] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[17] “Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.”  Vazquez-Mellado J.et.al.   16837472
[18] “PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.”  Gisler S.M.et.al.   14531806
[19] “The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.”  Anzai N.et.al.   15304510
[20] “Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.”  Ichida K.et.al.   14694169
[21] “A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese.”  Iwai N.et.al.   15327384
[22] “Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.”  Wakida N.et.al.   15634722
[23] “Mutational analysis of idiopathic renal hypouricemia in Korea.”  Cheong H.I.et.al.   15912381
[24] “Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.”  Graessler J.et.al.   16385546

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MAFSELLDLV GGLGRFQVLQ TMALMVSIMW LCTQSMLENF SAAVPSHRCW APLLDNSTAQ 
61:	ASILGSLSPE ALLAISIPPG PNQRPHQCRR FRQPQWQLLD PNATATSWSE ADTEPCVDGW 
121:	VYDRSIFTST IVAKWNLVCD SHALKPMAQS IYLAGILVGA AACGPASDRF GRRLVLTWSY 
181:	LQMAVMGTAA AFAPAFPVYC LFRFLLAFAV AGVMMNTGTL LMEWTAARAR PLVMTLNSLG 
241:	FSFGHGLTAA VAYGVRDWTL LQLVVSVPFF LCFLYSWWLA ESARWLLTTG RLDWGLQELW 
301:	RVAAINGKGA VQDTLTPEVL LSAMREELSM GQPPASLGTL LRMPGLRFRT CISTLCWFAF 
361:	GFTFFGLALD LQALGSNIFL LQMFIGVVDI PAKMGALLLL SHLGRRPTLA ASLLLAGLCI 
421:	LANTLVPHEM GALRSALAVL GLGGVGAAFT CITIYSSELF PTVLRMTAVG LGQMAARGGA 
481:	ILGPLVRLLG VHGPWLPLLV YGTVPVLSGL AALLLPETQS LPLPDTIQDV QNQAVKKATH 
541:	GTLGNSVLKS TQF