S22A6_MOUSE
ID S22A6_MOUSE Reviewed; 545 AA.
AC Q8VC69; Q61185;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Solute carrier family 22 member 6;
DE AltName: Full=Kidney-specific transport protein;
DE AltName: Full=Novel kidney transcript;
DE Short=mNKT;
DE AltName: Full=Organic anion transporter 1;
DE AltName: Full=Renal organic anion transporter 1;
DE Short=mROAT1;
GN Name=Slc22a6; Synonyms=Nkt, Oat1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, MUTAGENESIS OF CYS-49;
RP CYS-78; CYS-99; CYS-122; CYS-172; CYS-183; CYS-200; CYS-326; CYS-335;
RP CYS-379; CYS-402; CYS-427 AND CYS-434, AND SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Kidney;
RX PubMed=9045672; DOI=10.1074/jbc.272.10.6471;
RA Lopez-Nieto C.E., You G., Bush K.T., Barros E.J., Beier D.R., Nigam S.K.;
RT "Molecular cloning and characterization of NKT, a gene product related to
RT the organic cation transporter family that is almost exclusively expressed
RT in the kidney.";
RL J. Biol. Chem. 272:6471-6478(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=9880528; DOI=10.1074/jbc.274.3.1519;
RA Kuze K., Graves P., Leahy A., Wilson P., Stuhlmann H., You G.;
RT "Heterologous expression and functional characterization of a mouse renal
RT organic anion transporter in mammalian cells.";
RL J. Biol. Chem. 274:1519-1524(1999).
RN [5]
RP FUNCTION.
RX PubMed=10744714; DOI=10.1074/jbc.275.14.10278;
RA You G., Kuze K., Kohanski R.A., Amsler K., Henderson S.;
RT "Regulation of mOAT-mediated organic anion transport by okadaic acid and
RT protein kinase C in LLC-PK(1) cells.";
RL J. Biol. Chem. 275:10278-10284(2000).
RN [6]
RP FUNCTION.
RX PubMed=14979872; DOI=10.1042/bj20031724;
RA Tanaka K., Zhou F., Kuze K., You G.;
RT "Cysteine residues in the organic anion transporter mOAT1.";
RL Biochem. J. 380:283-287(2004).
RN [7]
RP MUTAGENESIS OF ASN-39, AND GLYCOSYLATION AT ASN-56; ASN-86; ASN-91 AND
RP ASN-107.
RX PubMed=14749323; DOI=10.1074/jbc.m400197200;
RA Tanaka K., Xu W., Zhou F., You G.;
RT "Role of glycosylation in the organic anion transporter OAT1.";
RL J. Biol. Chem. 279:14961-14966(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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), cidofovir, adefovir, 9-(2-
CC phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl)
CC diaminopurine (PMEDAP), ochratoxin (OTA), acyclovir (ACV), 3'-azido-
CC 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate
CC (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and
CC 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) and edaravone
CC sulfate (By similarity). Mediates the sodium-independent uptake of p-
CC aminohippurate (PAH). PAH uptake is inhibited by benzothiazolylcysteine
CC (BTC), S-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, probenecid, phenol red, urate, glutarate and
CC alpha-ketoglutarate (By similarity). PAH uptake is inhibited by p-
CC chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC),
CC indomethacin, sulindac, diclofenac, carprofen, okadaic acid and PKC
CC activators. {ECO:0000250, ECO:0000269|PubMed:10744714,
CC ECO:0000269|PubMed:14979872, ECO:0000269|PubMed:9880528}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37.3 uM for PAH {ECO:0000269|PubMed:9880528};
CC Vmax=210 pmol/min/mg enzyme for PAH uptake
CC {ECO:0000269|PubMed:9880528};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9045672};
CC Multi-pass membrane protein {ECO:0000269|PubMed:9045672}.
CC Note=Localized to the plasma membrane.
CC -!- TISSUE SPECIFICITY: Expressed in kidney; in the basolateral membrane
CC and at much lower levels in brain. {ECO:0000269|PubMed:9045672,
CC ECO:0000269|PubMed:9880528}.
CC -!- DEVELOPMENTAL STAGE: Developmentally regulated with significant
CC expression beginning at 18 dpc and rising just before birth.
CC -!- DOMAIN: Multiple cysteine residues are necessary for proper targeting
CC to the plasma membrane.
CC -!- PTM: Glycosylated. Glycosylation is necessary for proper targeting of
CC the transporter to the plasma membrane. {ECO:0000269|PubMed:14749323}.
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; U52842; AAC53112.1; -; mRNA.
DR EMBL; AK035971; BAC29261.1; -; mRNA.
DR EMBL; BC021647; AAH21647.1; -; mRNA.
DR CCDS; CCDS29538.1; -.
DR RefSeq; NP_032792.2; NM_008766.3.
DR AlphaFoldDB; Q8VC69; -.
DR SMR; Q8VC69; -.
DR BioGRID; 201976; 1.
DR STRING; 10090.ENSMUSP00000010250; -.
DR BindingDB; Q8VC69; -.
DR ChEMBL; CHEMBL5653; -.
DR DrugCentral; Q8VC69; -.
DR GlyGen; Q8VC69; 6 sites.
DR iPTMnet; Q8VC69; -.
DR PhosphoSitePlus; Q8VC69; -.
DR jPOST; Q8VC69; -.
DR MaxQB; Q8VC69; -.
DR PaxDb; Q8VC69; -.
DR PRIDE; Q8VC69; -.
DR ProteomicsDB; 260886; -.
DR Antibodypedia; 28866; 298 antibodies from 32 providers.
DR DNASU; 18399; -.
DR Ensembl; ENSMUST00000010250; ENSMUSP00000010250; ENSMUSG00000024650.
DR GeneID; 18399; -.
DR KEGG; mmu:18399; -.
DR UCSC; uc008gme.2; mouse.
DR CTD; 9356; -.
DR MGI; MGI:892001; Slc22a6.
DR VEuPathDB; HostDB:ENSMUSG00000024650; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000157004; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q8VC69; -.
DR OMA; PWHCTGV; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q8VC69; -.
DR TreeFam; TF315847; -.
DR Reactome; R-MMU-561048; Organic anion transport.
DR BioGRID-ORCS; 18399; 9 hits in 73 CRISPR screens.
DR ChiTaRS; Slc22a6; mouse.
DR PRO; PR:Q8VC69; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8VC69; protein.
DR Bgee; ENSMUSG00000024650; Expressed in right kidney and 74 other tissues.
DR Genevisible; Q8VC69; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0015301; F:anion:anion antiporter activity; ISO:MGI.
DR GO; GO:0031404; F:chloride ion binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0015742; P:alpha-ketoglutarate transport; ISS:UniProtKB.
DR GO; GO:0006820; P:anion transport; IDA:MGI.
DR GO; GO:0015711; P:organic anion transport; IMP:UniProtKB.
DR GO; GO:0097254; P:renal tubular secretion; IMP:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0043252; P:sodium-independent organic anion transport; ISO:MGI.
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..545
FT /note="Solute carrier family 22 member 6"
FT /id="PRO_0000324168"
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..129
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..242
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..389
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 411..419
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..478
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 479..499
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..545
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 515..545
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..545
FT /note="Polar residues"
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:0000269|PubMed:14749323"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 39
FT /note="N->Q: Complete loss of PAH transport activity."
FT /evidence="ECO:0000269|PubMed:14749323"
FT MUTAGEN 49
FT /note="C->A: Decrease in the level of cell surface
FT expression and transport function. Complete loss of
FT transport function; when associated with A-78; A-99; A-122;
FT A-172; A-183; A-200; A-362; A-335; A-379; A-402; A-427 and
FT A-434."
FT /evidence="ECO:0000269|PubMed:9045672"
FT MUTAGEN 122
FT /note="C->A: Decrease in the level of cell surface
FT expression and transport function. Complete loss of
FT transport function; when associated with A-49; A-78; A-99;
FT A-172; A-183; A-200; A-362; A-335; A-379; A-402; A-427 and
FT A-434."
FT /evidence="ECO:0000269|PubMed:9045672"
FT MUTAGEN 183
FT /note="C->A: Decrease in the level of cell surface
FT expression and transport function. Complete loss of
FT transport function; when associated with A-49; A-78; A-99;
FT A-122; A-172; A-200; A-362; A-335; A-379; A-402; A-427 and
FT A-434."
FT /evidence="ECO:0000269|PubMed:9045672"
FT MUTAGEN 434
FT /note="C->A: Decrease in the level of cell surface
FT expression and transport function. 80% decrease in the
FT level of transport activity; when associated with A-49; A-
FT 122 and A-183. Complete loss of transport function; when
FT associated with A-49; A-78; A-99; A-122; A-172; A-183; A-
FT 200; A-362; A-335; A-379; A-402 and A-427."
FT /evidence="ECO:0000269|PubMed:9045672"
FT CONFLICT 66
FT /note="W -> R (in Ref. 1; AAC53112)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 545 AA; 60013 MW; 827782E115705C77 CRC64;
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPAHHCR PPANANLSKD
GGLEAWLPLD KQGRPESCLR FPFPHNGTEA NGTGVTEPCL DGWVYDNSTF PSTIVTEWNL
VCSHRAFRQL AQSLFMVGVL LGAMMFGYLA DRLGRRKVLI LNYLQTAVSG TCAAYAPNYT
VYCIFRLLSG MSLASIAINC MTLNMEWMPI HTRAYVGTLI GYVYSLGQFL LAGIAYAVPH
WRHLQLAVSV PFFVAFIYSW FFIESARWYS SSGRLDLTLR ALQRVARING KQEEGAKLSI
EVLQTSLQKE LTLNKGQASA MELLRCPTLR RLFLCLSMLW FATSFAYYGL VMDLQGFGVS
MYLIQVIFGA VDLPAKFVCF LVINSMGRRP AQLASLLLAG ICILVNGIIP RGHTIIRTSL
AVLGKGCLAS SFNCIFLYTG ELYPTMIRQT GLGMGSTMAR VGSIVSPLIS MTAEFYPSIP
LFIFGAVPVA ASAVTALLPE TLGQPLPDTV QDLKSRSRGK QKQQQLEQQK QMIPLQVSTQ
EKNGL
