S22AC_RAT
ID S22AC_RAT Reviewed; 553 AA.
AC Q3ZAV1;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Solute carrier family 22 member 12;
DE AltName: Full=Urate anion exchanger 1;
GN Name=Slc22a12; Synonyms=Urat1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=21074513; DOI=10.1016/j.bbamem.2010.11.002;
RA Sato M., Wakayama T., Mamada H., Shirasaka Y., Nakanishi T., Tamai I.;
RT "Identification and functional characterization of uric acid transporter
RT Urat1 (Slc22a12) in rats.";
RL Biochim. Biophys. Acta 1808:1441-1447(2011).
CC -!- FUNCTION: Major urate transporter involved in renal reabsorption of
CC urate and helps to maintain blood levels of uric acid
CC (PubMed:21074513). Translocates urate over the apical membrane of
CC proximal tubular cells in exchange for organic anions or chloride ions
CC (PubMed:21074513). {ECO:0000269|PubMed:21074513}.
CC -!- ACTIVITY REGULATION: Inhibited by benzbromarone and stimulated by
CC lactate and pyrazinecarboxylic acid. {ECO:0000269|PubMed:21074513}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1773 uM for urate {ECO:0000269|PubMed:21074513};
CC Vmax=31.6 pmol/min/mg enzyme for urate transport
CC {ECO:0000269|PubMed:21074513};
CC pH dependence:
CC Optimum pH is 7.4. {ECO:0000269|PubMed:21074513};
CC -!- SUBUNIT: Interacts with PDZK1. {ECO:0000250|UniProtKB:Q96S37}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21074513};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000269|PubMed:21074513}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the proximal tubular epithelial cells
CC in kidney. {ECO:0000269|PubMed:21074513}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8CFZ5}.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC103638; AAI03639.1; -; mRNA.
DR RefSeq; NP_001030115.1; NM_001034943.1.
DR RefSeq; XP_008758383.1; XM_008760161.2.
DR RefSeq; XP_008758384.1; XM_008760162.2.
DR AlphaFoldDB; Q3ZAV1; -.
DR SMR; Q3ZAV1; -.
DR STRING; 10116.ENSRNOP00000028665; -.
DR BindingDB; Q3ZAV1; -.
DR ChEMBL; CHEMBL1075239; -.
DR GlyGen; Q3ZAV1; 3 sites.
DR iPTMnet; Q3ZAV1; -.
DR PhosphoSitePlus; Q3ZAV1; -.
DR PaxDb; Q3ZAV1; -.
DR Ensembl; ENSRNOT00000092270; ENSRNOP00000075925; ENSRNOG00000021108.
DR GeneID; 365398; -.
DR KEGG; rno:365398; -.
DR UCSC; RGD:621628; rat.
DR CTD; 116085; -.
DR RGD; 621628; Slc22a12.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162485; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q3ZAV1; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q3ZAV1; -.
DR TreeFam; TF315847; -.
DR Reactome; R-RNO-561048; Organic anion transport.
DR PRO; PR:Q3ZAV1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021108; Expressed in adult mammalian kidney and 7 other tissues.
DR ExpressionAtlas; Q3ZAV1; baseline and differential.
DR Genevisible; Q3ZAV1; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0015143; F:urate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0015711; P:organic anion transport; IBA:GO_Central.
DR GO; GO:0097744; P:renal urate salt excretion; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR GO; GO:0046415; P:urate metabolic process; ISO:RGD.
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 Cell membrane; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..553
FT /note="Solute carrier family 22 member 12"
FT /id="PRO_0000307946"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
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 534
FT /note="Phosphoserine"
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 CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 553 AA; 60245 MW; A264F7CFD937CCD8 CRC64;
MAFPELLDRV GGRGRFQLLQ AVALVTPILW VTTQNMLENF SAAVPHHRCW VPLLDNSTSQ
ASIPGDFGRD VLLAVSIPPG PDQRPHQCLR FRQPQWQLIE SNTTATNWSD ADTEPCEDGW
VYDHSTFRST IVTTWDLVCD SQALRPMAQS IFLAGILVGA AVCGHASDRF GRRRVLTWSY
LLVSVSGTIA ALMPTFPLYC LFRFLVASAV AGVMMNTASL LMEWTSAQAG PLMMTLNALG
FSFGQVLTGS VAYGVRSWRM LQLAVSAPFF LFFVYSWWLP ESARWLITVG RLDQSLRELQ
RVAAVNRRKA EADTLTVEVL RSAMQEEPNG NQAGARLGTL LHTPGLRLRT FISMLCWFAF
GFTFYGLALD LQALGSNIFL LQALIGIVDL PVKMGSLLLL SRLGRRLCQA SSLVLPGLCI
LANILVPREM GILRSSLAVL GLGSLGAAFT CVTIFSSELF PTVIRMTAVG LGQVAARGGA
MLGPLVRLLG VYGSWLPLLV YGVVPVLSGL AALLLPETKN LPLPDTIQDI QKQSVKKVTH
DIAGGSVLKS ARL
