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Protein

Solute carrier family 22 member 12

Gene

SLC22A12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cellular homeostasis Source: UniProtKB
  • response to drug Source: UniProtKB
  • sodium-independent organic anion transport Source: GO_Central
  • urate metabolic process Source: BHF-UCL
  • urate transport Source: UniProtKB

Keywordsi

Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-561048 Organic anion transport
R-HSA-5619071 Defective SLC22A12 causes renal hypouricemia 1 (RHUC1)

Protein family/group databases

TCDBi2.A.1.19.11 the major facilitator superfamily (mfs)

Names & Taxonomyi

Protein namesi
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 namesi
Name:SLC22A12
Synonyms:OATL4, URAT1
ORF Names:UNQ6453/PRO34004
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000197891.11
HGNCiHGNC:17989 SLC22A12
MIMi607096 gene
neXtProtiNX_Q96S37

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei9 – 29HelicalSequence analysisAdd BLAST21
Transmembranei146 – 166HelicalSequence analysisAdd BLAST21
Transmembranei174 – 194HelicalSequence analysisAdd BLAST21
Transmembranei195 – 215HelicalSequence analysisAdd BLAST21
Transmembranei232 – 252HelicalSequence analysisAdd BLAST21
Transmembranei260 – 280HelicalSequence analysisAdd BLAST21
Transmembranei351 – 371HelicalSequence analysisAdd BLAST21
Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
Transmembranei407 – 427HelicalSequence analysisAdd BLAST21
Transmembranei435 – 455HelicalSequence analysisAdd BLAST21
Transmembranei466 – 486HelicalSequence analysisAdd BLAST21
Transmembranei495 – 515HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypouricemia renal 1 (RHUC1)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:220150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03672190R → H in RHUC1; strongly reduced urate transport. 3 PublicationsCorresponds to variant dbSNP:rs121907896EnsemblClinVar.1
Natural variantiVAR_036723138V → M in RHUC1; strongly reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs149722479Ensembl.1
Natural variantiVAR_036724164G → S in RHUC1; reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs201181059Ensembl.1
Natural variantiVAR_036725217T → M in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs121907893EnsemblClinVar.1
Natural variantiVAR_036730298E → D in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs121907894EnsemblClinVar.1
Natural variantiVAR_036733313 – 333Missing in RHUC1; unknown pathological significance; affects urate transport. 1 PublicationAdd BLAST21
Natural variantiVAR_075344366G → R in RHUC1; reduced urate transport; reduced localization at the plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs1047976958Ensembl.1
Natural variantiVAR_036734382Q → L in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs765990518EnsemblClinVar.1
Natural variantiVAR_036735418L → R in RHUC1; strongly reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs121907895EnsemblClinVar.1
Natural variantiVAR_036736430M → T in RHUC1; reduced urate transport. 1 Publication1
Natural variantiVAR_036737477R → H in RHUC1. 3 PublicationsCorresponds to variant dbSNP:rs773677616Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi116085
MalaCardsiSLC22A12
MIMi220150 phenotype
OpenTargetsiENSG00000197891
Orphaneti94088 Hereditary renal hypouricemia
PharmGKBiPA38478

Chemistry databases

ChEMBLiCHEMBL6120
DrugBankiDB11560 Lesinurad
DB00678 Losartan
DB01032 Probenecid
GuidetoPHARMACOLOGYi1031

Polymorphism and mutation databases

DMDMi74732700

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003079441 – 553Solute carrier family 22 member 12Add BLAST553

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi102N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei542PhosphothreonineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ96S37
PeptideAtlasiQ96S37
PRIDEiQ96S37
ProteomicsDBi78060
78061 [Q96S37-2]

PTM databases

PhosphoSitePlusiQ96S37

Expressioni

Tissue specificityi

Detected in kidney (at protein level). Detected in fetal and adult kidney. Detected in epithelial cells of proximal tubules in renal cortex.2 Publications

Gene expression databases

BgeeiENSG00000197891
CleanExiHS_SLC22A12
GenevisibleiQ96S37 HS

Organism-specific databases

HPAiHPA024575

Interactioni

Subunit structurei

Interacts with PDZK1.2 Publications

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi125471, 4 interactors
IntActiQ96S37, 1 interactor
MINTiQ96S37
STRINGi9606.ENSP00000366797

Chemistry databases

BindingDBiQ96S37

Structurei

3D structure databases

ProteinModelPortaliQ96S37
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0255 Eukaryota
COG0477 LUCA
GeneTreeiENSGT00760000118852
HOVERGENiHBG108433
InParanoidiQ96S37
KOiK08208
OMAiLMEWTAA
OrthoDBiEOG091G068G
PhylomeDBiQ96S37
TreeFamiTF315847

Family and domain databases

CDDicd06174 MFS, 1 hit
InterProiView protein in InterPro
IPR020846 MFS_dom
IPR005828 MFS_sugar_transport-like
IPR036259 MFS_trans_sf
PfamiView protein in Pfam
PF00083 Sugar_tr, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit
PROSITEiView protein in PROSITE
PS50850 MFS, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96S37-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAFSELLDLV GGLGRFQVLQ TMALMVSIMW LCTQSMLENF SAAVPSHRCW
60 70 80 90 100
APLLDNSTAQ ASILGSLSPE ALLAISIPPG PNQRPHQCRR FRQPQWQLLD
110 120 130 140 150
PNATATSWSE ADTEPCVDGW VYDRSIFTST IVAKWNLVCD SHALKPMAQS
160 170 180 190 200
IYLAGILVGA AACGPASDRF GRRLVLTWSY LQMAVMGTAA AFAPAFPVYC
210 220 230 240 250
LFRFLLAFAV AGVMMNTGTL LMEWTAARAR PLVMTLNSLG FSFGHGLTAA
260 270 280 290 300
VAYGVRDWTL LQLVVSVPFF LCFLYSWWLA ESARWLLTTG RLDWGLQELW
310 320 330 340 350
RVAAINGKGA VQDTLTPEVL LSAMREELSM GQPPASLGTL LRMPGLRFRT
360 370 380 390 400
CISTLCWFAF GFTFFGLALD LQALGSNIFL LQMFIGVVDI PAKMGALLLL
410 420 430 440 450
SHLGRRPTLA ASLLLAGLCI LANTLVPHEM GALRSALAVL GLGGVGAAFT
460 470 480 490 500
CITIYSSELF PTVLRMTAVG LGQMAARGGA ILGPLVRLLG VHGPWLPLLV
510 520 530 540 550
YGTVPVLSGL AALLLPETQS LPLPDTIQDV QNQAVKKATH GTLGNSVLKS

TQF
Length:553
Mass (Da):59,630
Last modified:December 1, 2001 - v1
Checksum:iE3F29F38129BAD61
GO
Isoform 2 (identifier: Q96S37-2) [UniParc]FASTAAdd to basket

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

Show »
Length:445
Mass (Da):47,648
Checksum:i5385EA4A75ABD7C4
GO
Isoform 3 (identifier: Q96S37-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-221: Missing.

Show »
Length:332
Mass (Da):35,570
Checksum:i0080739C739B384B
GO
Isoform 4 (identifier: Q96S37-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     187-221: GTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLL → V

Show »
Length:519
Mass (Da):56,094
Checksum:iA29300D5DC37247A
GO

Sequence cautioni

The sequence BAB68364 differs from that shown. Reason: Frameshift at positions 84 and 136.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti451C → Y in AAQ88550 (PubMed:12975309).Curated1
Sequence conflicti538A → T in AK315061 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03672065G → W. Corresponds to variant dbSNP:rs12800450Ensembl.1
Natural variantiVAR_03672190R → H in RHUC1; strongly reduced urate transport. 3 PublicationsCorresponds to variant dbSNP:rs121907896EnsemblClinVar.1
Natural variantiVAR_03672292R → C1 PublicationCorresponds to variant dbSNP:rs144328876Ensembl.1
Natural variantiVAR_036723138V → M in RHUC1; strongly reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs149722479Ensembl.1
Natural variantiVAR_036724164G → S in RHUC1; reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs201181059Ensembl.1
Natural variantiVAR_036725217T → M in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs121907893EnsemblClinVar.1
Natural variantiVAR_036726226A → V1 PublicationCorresponds to variant dbSNP:rs145738825Ensembl.1
Natural variantiVAR_036727284R → G in some gout patients; uncertain pathological significance. 1 Publication1
Natural variantiVAR_036728290G → C in some gout patients; uncertain pathological significance. 1 Publication1
Natural variantiVAR_036729297Q → E in some gout patients; uncertain pathological significance. 1 Publication1
Natural variantiVAR_036730298E → D in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs121907894EnsemblClinVar.1
Natural variantiVAR_036731305I → S in some gout patients; uncertain pathological significance. 1 Publication1
Natural variantiVAR_036732312Q → L1 Publication1
Natural variantiVAR_036733313 – 333Missing in RHUC1; unknown pathological significance; affects urate transport. 1 PublicationAdd BLAST21
Natural variantiVAR_075344366G → R in RHUC1; reduced urate transport; reduced localization at the plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs1047976958Ensembl.1
Natural variantiVAR_036734382Q → L in RHUC1; strongly reduced urate transport. 2 PublicationsCorresponds to variant dbSNP:rs765990518EnsemblClinVar.1
Natural variantiVAR_036735418L → R in RHUC1; strongly reduced urate transport. 1 PublicationCorresponds to variant dbSNP:rs121907895EnsemblClinVar.1
Natural variantiVAR_036736430M → T in RHUC1; reduced urate transport. 1 Publication1
Natural variantiVAR_036737477R → H in RHUC1. 3 PublicationsCorresponds to variant dbSNP:rs773677616Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0540541 – 221Missing in isoform 3. CuratedAdd BLAST221
Alternative sequenceiVSP_028879170 – 277Missing in isoform 2. 1 PublicationAdd BLAST108
Alternative sequenceiVSP_054055187 – 221GTAAA…TGTLL → V in isoform 4. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB071863 mRNA Translation: BAB96750.1
AC044790 Genomic DNA Translation: AAK68156.1
AY358183 mRNA Translation: AAQ88550.1
AB050269 mRNA Translation: BAB68364.1 Frameshift.
AK315061 mRNA No translation available.
AP001092 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW74273.1
CH471076 Genomic DNA Translation: EAW74274.1
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
CCDSiCCDS60835.1 [Q96S37-4]
CCDS60836.1 [Q96S37-2]
CCDS8075.1 [Q96S37-1]
RefSeqiNP_001263255.1, NM_001276326.1 [Q96S37-4]
NP_001263256.1, NM_001276327.1 [Q96S37-2]
NP_653186.2, NM_144585.3 [Q96S37-1]
NP_700357.1, NM_153378.2 [Q96S37-3]
UniGeneiHs.174424
Hs.700182

Genome annotation databases

EnsembliENST00000336464; ENSP00000336836; ENSG00000197891 [Q96S37-4]
ENST00000377567; ENSP00000366790; ENSG00000197891 [Q96S37-2]
ENST00000377572; ENSP00000366795; ENSG00000197891 [Q96S37-2]
ENST00000377574; ENSP00000366797; ENSG00000197891 [Q96S37-1]
ENST00000473690; ENSP00000438437; ENSG00000197891 [Q96S37-3]
GeneIDi116085
KEGGihsa:116085
UCSCiuc001oal.3 human [Q96S37-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiS22AC_HUMAN
AccessioniPrimary (citable) accession number: Q96S37
Secondary accession number(s): B7WPG1
, G3XAN7, Q19PF7, Q19PF8, Q19PF9, Q19PG0, Q6UXW3, Q96DT2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: December 1, 2001
Last modified: June 20, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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