S22A6_PSEAM
ID S22A6_PSEAM Reviewed; 562 AA.
AC O57379;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Solute carrier family 22 member 6;
DE AltName: Full=Organic anion transporter 1;
DE AltName: Full=Renal organic anion transporter 1;
DE Short=ROAT1;
DE AltName: Full=fROAT1;
GN Name=SLC22A6; Synonyms=OAT1;
OS Pseudopleuronectes americanus (Winter flounder) (Pleuronectes americanus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Carangaria; Pleuronectiformes; Pleuronectoidei; Pleuronectidae;
OC Pseudopleuronectes.
OX NCBI_TaxID=8265;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND
RP MUTAGENESIS OF HIS-34; LYS-394 AND ARG-478.
RC TISSUE=Kidney;
RX PubMed=9409735; DOI=10.1016/s0014-5793(97)01304-5;
RA Wolff N.A., Werner A., Burkhardt S., Burckhardt G.;
RT "Expression cloning and characterization of a renal organic anion
RT transporter from winter flounder.";
RL FEBS Lett. 417:287-291(1997).
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 p-aminohippurate (PAH), 2,3-
CC dimercapto-1-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), 3-
CC 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 p-
CC chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC),
CC indomethacin, sulindac, diclofenac, carprofen, okadaic acid,
CC benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC),
CC cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide,
CC steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore
CC A23187, benzylpenicillin, bumetamide, losartan, probenecid, phenol red,
CC urate, glutarate and alpha-ketoglutarate (By similarity). PAH uptake is
CC inhibited by glutarate. {ECO:0000250, ECO:0000269|PubMed:9409735}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for PAH {ECO:0000269|PubMed:9409735};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
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; Z97028; CAB09724.1; -; mRNA.
DR AlphaFoldDB; O57379; -.
DR SMR; O57379; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
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; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..562
FT /note="Solute carrier family 22 member 6"
FT /id="PRO_0000324174"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..205
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 282..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..378
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..408
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 430..444
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..468
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..489
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 490..495
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 517..562
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MUTAGEN 34
FT /note="H->I: Reduced transport activity."
FT /evidence="ECO:0000269|PubMed:9409735"
FT MUTAGEN 394
FT /note="K->A: Reduced transport activity."
FT /evidence="ECO:0000269|PubMed:9409735"
FT MUTAGEN 478
FT /note="R->D: Reduced transport activity."
FT /evidence="ECO:0000269|PubMed:9409735"
SQ SEQUENCE 562 AA; 61993 MW; 7DC1A67F32801D2D CRC64;
MPFSELLEQV GSTGRFQVLH VTLLCIPVLM MASHNLLQNF VATVPSHYCN AHANLSQARL
SLEESLLITV PLDGAGKPQR CQRYAAPQWH LLGKNGTSGS GDLADATESM DAALQECSDG
WSYNSTVRSS TIISEWHLVC DMHSFKQMGQ TIYMGGVLVG ALLFGGLSDR YGRRILLLIS
NLLMAVSGTC AAFSSSFSLF CVFRFGCGLA LSGLGLNTFS LIVEWIPTRI RTAVGTTTGY
CYTLGQLILV LLAYFIRDWR WLTLAVSLPF YVFFLIAWWF HESSRWLALS NRTEHALKNL
KSVARFNGRH EEAEKLDIKM LHESMKKEMS CTQGSYSILD LFNTPAMRKR TLCLSAVWLS
TSFAYYGLAM DLDKFGVDIY LIQVIFGAVD IPAKVVVVVS MSLIGRRRSQ CAVLVVAGIT
ILLNLLVPYD KQTIRTCLAV LGKGCLAASF NCCYLYSGEL FPTIIRQNGM GWVSMMARIG
AMVAPMVLLT RDYIPWLPGL IYGGAPILSG LAAIFLPETL GYPLPDTIQD VEESGSGRKS
KMSTKETITL QDKQANLLKQ SA
