S22A6_MACFA
ID S22A6_MACFA Reviewed; 550 AA.
AC Q4W8A3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Solute carrier family 22 member 6;
DE AltName: Full=Organic anion transporter 1;
DE AltName: Full=Renal organic anion transporter 1;
GN Name=SLC22A6; Synonyms=OAT1;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Kidney;
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).
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), chloromercuribenzenesulphonate (PCMBS), diethyl
CC pyrocarbonate (DEPC), and edaravone sulfate (By similarity). Mediates
CC the sodium-independent uptake of p-aminohippurate (PAH), 2,4-dichloro-
CC phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), cimetidine
CC (CMD), indoxyl sulfate (IS), ochratoxin (OTA), acyclovir (ACV), 3'-
CC azido-3-'deoxythymidine (AZT), and 3-carboxy-4-methyl-5-propyl-2-
CC furanpropionate (CMPF). PAH uptake is inhibited by furosemide, steviol,
CC phorbol 12-myristate 13-acetate (PMA), diclofenac, carprofen, sulindac,
CC calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin,
CC bumetamide, losartan, probenecid, phenol red, urate, okadaic acid,
CC benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC),
CC cysteine S-conjugates S-dichlorovinylcysteine (DCVC), glutarate and
CC alpha-ketoglutarate (By similarity). {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.1 uM for PAH {ECO:0000269|PubMed:15846473};
CC KM=3 uM for 2,4-D {ECO:0000269|PubMed:15846473};
CC KM=12.2 uM for HA {ECO:0000269|PubMed:15846473};
CC KM=23.6 uM for IA {ECO:0000269|PubMed:15846473};
CC KM=32.9 uM for IS {ECO:0000269|PubMed:15846473};
CC KM=85.3 uM for CMPF {ECO:0000269|PubMed:15846473};
CC Vmax=502 pmol/min/mg enzyme for PAH uptake
CC {ECO:0000269|PubMed:15846473};
CC Vmax=272 pmol/min/mg enzyme for 2,4-D uptake
CC {ECO:0000269|PubMed:15846473};
CC Vmax=702 pmol/min/mg enzyme for HA uptake
CC {ECO:0000269|PubMed:15846473};
CC Vmax=150 pmol/min/mg enzyme for IA uptake
CC {ECO:0000269|PubMed:15846473};
CC Vmax=270 pmol/min/mg enzyme for IS uptake
CC {ECO:0000269|PubMed:15846473};
CC Vmax=478 pmol/min/mg enzyme for CMPF uptake
CC {ECO:0000269|PubMed:15846473};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney; in the basolateral membrane of
CC the proximal tubule. {ECO:0000269|PubMed:15846473}.
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; AB182992; BAD99107.1; -; mRNA.
DR RefSeq; NP_001274626.1; NM_001287697.1.
DR AlphaFoldDB; Q4W8A3; -.
DR SMR; Q4W8A3; -.
DR STRING; 9541.XP_005577585.1; -.
DR Ensembl; ENSMFAT00000008223; ENSMFAP00000033995; ENSMFAG00000003484.
DR GeneID; 102120909; -.
DR VEuPathDB; HostDB:ENSMFAG00000003484; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000157004; -.
DR OMA; PWHCTGV; -.
DR Proteomes; UP000233100; Chromosome 14.
DR Bgee; ENSMFAG00000003484; Expressed in adult mammalian kidney and 3 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005452; F:inorganic anion exchanger activity; ISS:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015742; P:alpha-ketoglutarate transport; ISS:UniProtKB.
DR GO; GO:0015711; P:organic anion transport; ISS:UniProtKB.
DR GO; GO:0097254; P:renal tubular secretion; ISS: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 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..550
FT /note="Solute carrier family 22 member 6"
FT /id="PRO_0000324167"
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..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..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..456
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 457..477
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 478..484
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 506..550
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 513..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 550 AA; 60192 MW; 9BCAF0A249E158BB CRC64;
MAFNDLLQQV GGVGRFQQIQ VTLVVLPLLL MASHNTVQNF TAAIPTHHCR PPANANLSKD
GGLEAWLPRD RQGQPESCLR FTSPQWGPPF PNGTEANGTG ATEPCTDGWI YDNSTFPSTI
VTEWDLVCSH RALRQLAQSL YMVGVLLGAM VFGYLADRLG RRKVLILNYL QTAVSGTCAA
FAPNFPIYCA FRLLSGMSLA GIALNCMTLN VEWMPIHTRA CVGTLIGYVY SLGQFLLAGV
AYAVPHWRHL QLLISVPFFA FFIYSWFFIE SARWHSSSGR LDLTLRALQR VARINGKREE
GAKLSMEVLR ASLQKELTMG KGQASAMELL RCPTLRHLFL CLSMLWFATS FAYYGLVMDL
QGFGVSIYLI QVIFGAVDLP AKLVGFLVIN SLGRRPAQMA ALLLAGICIL LNGVVPQDQS
VIRTSLAVLG KGCLAASFNC IFLYTGELYP TMIRQTGLGM GSTMARVGSI VSPLVSMTTE
LYPSVPLFIY GAVPVAASAV TVLLPETLGQ PLPDTVQDLE SRKGKQTPQQ QEHQKYMVPL
QASAQEKNGL
