S22A6_RAT
ID S22A6_RAT Reviewed; 551 AA.
AC O35956;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Solute carrier family 22 member 6;
DE AltName: Full=Organic anion transporter 1;
DE Short=rOAT1;
DE AltName: Full=renal organic anion transporter 1;
DE Short=rROAT1;
GN Name=Slc22a6; Synonyms=Oat1;
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 [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9374486; DOI=10.1074/jbc.272.48.30088;
RA Sweet D.H., Wolff N.A., Pritchard J.B.;
RT "Expression cloning and characterization of ROAT1. The basolateral organic
RT anion transporter in rat kidney.";
RL J. Biol. Chem. 272:30088-30095(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=9228014; DOI=10.1074/jbc.272.30.18526;
RA Sekine T., Watanabe N., Hosoyamada M., Kanai Y., Endou H.;
RT "Expression cloning and characterization of a novel multispecific organic
RT anion transporter.";
RL J. Biol. Chem. 272:18526-18529(1997).
RN [3]
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 [4]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10462545; DOI=10.1124/mol.56.3.570;
RA Cihlar T., Lin D.C., Pritchard J.B., Fuller M.D., Mendel D.B., Sweet D.H.;
RT "The antiviral nucleotide analogs cidofovir and adefovir are novel
RT substrates for human and rat renal organic anion transporter 1.";
RL Mol. Pharmacol. 56:570-580(1999).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15846473; DOI=10.1007/s11095-005-2503-0;
RA Tahara H., Shono M., Kusuhara H., Kinoshita H., Fuse E., Takadate A.,
RA Otagiri M., Sugiyama Y.;
RT "Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus
RT monkey kidney.";
RL Pharm. Res. 22:647-660(2005).
RN [6]
RP INDUCTION BY PGE2.
RX PubMed=16338963; DOI=10.1681/asn.2005070727;
RA Sauvant C., Holzinger H., Gekle M.;
RT "Prostaglandin E2 inhibits its own renal transport by downregulation of
RT organic anion transporters rOAT1 and rOAT3.";
RL J. Am. Soc. Nephrol. 17:46-53(2006).
RN [7]
RP INDUCTION.
RX PubMed=17245393; DOI=10.1038/sj.ki.5002104;
RA Matsuzaki T., Watanabe H., Yoshitome K., Morisaki T., Hamada A.,
RA Nonoguchi H., Kohda Y., Tomita K., Inui K., Saito H.;
RT "Downregulation of organic anion transporters in rat kidney under
RT ischemia/reperfusion-induced acute renal failure.";
RL Kidney Int. 71:539-547(2007).
CC -!- FUNCTION: Involved in the renal elimination of endogenous and exogenous
CC organic anions. Functions as organic anion exchanger when the uptake of
CC one molecule of organic anion is coupled with an efflux of one molecule
CC of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc).
CC Mediates the sodium-independent uptake of 2,3-dimercapto-1-
CC propanesulfonic acid (DMPS), 9-(2-phosphonylmethoxyethyl) guanine
CC (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP), ochratoxin
CC (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine
CC (CMD) and edaravone sulfate. Mediates the sodium-independent uptake of
CC p-aminohippurate (PAH), cidofovir, adefovir, 2,4-dichloro-
CC phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl
CC sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF).
CC PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS),
CC diethyl pyrocarbonate (DEPC), indomethacin, sulindac, diclofenac,
CC carprofen, okadaic acid, benzothiazolylcysteine (BTC), S-
CC chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-
CC dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate
CC 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin,
CC bumetamide, losartan, phenol red, urate and alpha-ketoglutarate (By
CC similarity). PAH uptake is inhibited by glutarate and probenecid.
CC {ECO:0000250, ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.3 uM for PAH {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=238 uM for cidofovir {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=270 uM for adefovir {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=10.2 uM for 2,4-D {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=27.5 uM for HA {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=47.1 uM for IA {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=17.7 uM for IS {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC KM=154 uM for CMPF {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:15846473, ECO:0000269|PubMed:9228014,
CC ECO:0000269|PubMed:9374486};
CC Vmax=1270 pmol/min/mg enzyme for 2,4-D uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:15846473,
CC ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486};
CC Vmax=519 pmol/min/mg enzyme for HA uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:15846473,
CC ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486};
CC Vmax=387 pmol/min/mg enzyme for IA uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:15846473,
CC ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486};
CC Vmax=350 pmol/min/mg enzyme for IS uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:15846473,
CC ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486};
CC Vmax=1669 pmol/min/mg enzyme for CMPF uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:15846473,
CC ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney; in the particular
CC segment of the proximal tubule and to a lower extent in brain. Found
CC preferentially in the cortex and outer medulla and weakly in the inner
CC medulla. {ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486}.
CC -!- INDUCTION: Down-regulated by PGE2 and in ischemic kidney.
CC {ECO:0000269|PubMed:16338963, ECO:0000269|PubMed:17245393}.
CC -!- DOMAIN: Multiple cysteine residues are necessary for proper targeting
CC to the plasma membrane. {ECO:0000250}.
CC -!- PTM: Glycosylated. Glycosylation is necessary for proper targeting of
CC the transporter to the plasma membrane (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
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DR EMBL; AF008221; AAC18772.1; -; mRNA.
DR EMBL; AB004559; BAA22086.1; -; mRNA.
DR EMBL; BC104692; AAI04693.1; -; mRNA.
DR RefSeq; NP_058920.1; NM_017224.2.
DR AlphaFoldDB; O35956; -.
DR SMR; O35956; -.
DR BioGRID; 248147; 1.
DR IntAct; O35956; 1.
DR STRING; 10116.ENSRNOP00000024756; -.
DR BindingDB; O35956; -.
DR ChEMBL; CHEMBL1777665; -.
DR DrugCentral; O35956; -.
DR TCDB; 2.A.1.19.4; the major facilitator superfamily (mfs).
DR GlyGen; O35956; 4 sites.
DR PaxDb; O35956; -.
DR Ensembl; ENSRNOT00000024757; ENSRNOP00000024756; ENSRNOG00000018215.
DR GeneID; 29509; -.
DR KEGG; rno:29509; -.
DR UCSC; RGD:69338; rat.
DR CTD; 9356; -.
DR RGD; 69338; Slc22a6.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000157004; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; O35956; -.
DR OMA; PWHCTGV; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; O35956; -.
DR TreeFam; TF315847; -.
DR Reactome; R-RNO-561048; Organic anion transport.
DR SABIO-RK; O35956; -.
DR PRO; PR:O35956; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018215; Expressed in adult mammalian kidney and 12 other tissues.
DR Genevisible; O35956; RN.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0015301; F:anion:anion antiporter activity; IDA:RGD.
DR GO; GO:0031404; F:chloride ion binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0005452; F:inorganic anion exchanger activity; ISS:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015742; P:alpha-ketoglutarate transport; ISS:UniProtKB.
DR GO; GO:0006820; P:anion transport; ISO:RGD.
DR GO; GO:0015711; P:organic anion transport; IDA:MGI.
DR GO; GO:0097254; P:renal tubular secretion; ISS:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043252; P:sodium-independent organic anion transport; IDA:RGD.
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 InterPro; IPR004749; Orgcat_transp/SVOP.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00898; 2A0119; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..551
FT /note="Solute carrier family 22 member 6"
FT /id="PRO_0000324171"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..425
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..484
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 506..551
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 514..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 551 AA; 60766 MW; 8BA47BE628324BF2 CRC64;
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR PPANANLSKD
GGLEAWLPLD KQGQPESCLR FTSPQWGPPF YNGTEANGTR VTEPCIDGWV YDNSTFPSTI
VTEWNLVCSH RAFRQLAQSL YMVGVLLGAM VFGYLADRLG RRKVLILNYL QTAVSGTCAA
YAPNYTVYCV FRLLSGMSLA SIAINCMTLN VEWMPIHTRA YVGTLIGYVY SLGQFLLAGI
AYAVPHWRHL QLVVSVPFFI AFIYSWFFIE SARWYSSSGR LDLTLRALQR VARINGKQEE
GAKLSIEVLR TSLQKELTLS KGQASAMELL RCPTLRHLFL CLSMLWFATS FAYYGLVMDL
QGFGVSMYLI QVIFGAVDLP AKFVCFLVIN SMGRRPAQMA SLLLAGICIL VNGIIPKSHT
IIRTSLAVLG KGCLASSFNC IFLYTGELYP TVIRQTGLGM GSTMARVGSI VSPLVSMTAE
FYPSMPLFIF GAVPVVASAV TALLPETLGQ PLPDTVQDLK SRSRGKQNQQ QQEQQKQMMP
LQASTQEKNG L
