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solute carrier family 22 member 6 (organic cation transporter 1, hOAT1, renal organic anion transporter 1, hROAT1, PAH transporter, hPAHT, SLC22A6, OAT1, PAHT)
Function:
- role in the renal elimination of endogenous & exogenous organic anions
- mediates the Na+-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (putative)
- mediates the Na+-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) & 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) & edaravone sulfate.
- p-aminohippurate uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate & okadaic acid (putative), benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), Ca+2ophore A23187, benzylpenicillin, indomethacin, bumetanide, losartan, probenecid, phenol red, urate, & alpha-ketoglutarate
Kinetic parameters:
- KM=9.3 uM for PAH (isoform 1)
- KM=4 uM for PAH (isoform 2)
- KM=11 uM for edaravone
- KM=46 uM for cidofovir
- KM=30 uM for adefovir
- KM=5.77 uM for 2,4-D
- KM=23.5 uM for HA
- KM=14 uM for IA
- KM=20.5 uM for IS
- KM=141 uM for CMPF
- Vmax=534 pmol/min/mg enzyme for 2,4-D uptake
- Vmax=430 pmol/min/mg enzyme for HA uptake
- Vmax=110 pmol/min/mg enzyme for IA uptake
- Vmax=216 pmol/min/mg enzyme for IS uptake
- Vmax=801 pmol/min/mg enzyme for CMPF uptake
Structure:
- glycosylated
- glycosylation at Asn-113 may occur at a secondary level
- glycosylation is necessary for proper targeting of the transporter to the plasma membrane
- multiple Cys are necessary for proper targeting to the plasma membrane (putative)
- belongs to the major facilitator superfamily, organic cation transporter family
Compartment: cell membrane
Alternative splicing: named isoforms=4
Expression:
- expressed in kidney > liver, skeletal muscle, brain & placenta
- found at the basolateral membrane of the proximal tubule
General
glycoprotein
membrane protein
solute carrier family 22 (SLC22, SLC22A)
transmembrane 12 protein
Properties
SIZE: entity length = 563 aa
MW = 62 kD
COMPARTMENT: cellular membrane
MOTIF: cytoplasmic domain {1-9}
transmembrane domain {10-30}
exoplasmic loop {31-135}
MOTIF: N-glycosylation site {N39}
N-glycosylation site {N56}
N-glycosylation site {N92}
N-glycosylation site {N97}
N-glycosylation site {N113}
transmembrane domain {136-156}
cytoplasmic loop {157-164}
transmembrane domain {165-187}
exoplasmic loop {188-190}
transmembrane domain {191-213}
cytoplasmic loop {214-224}
transmembrane domain {225-245}
exoplasmic loop {246-248}
transmembrane domain {249-269}
cytoplasmic loop {270-337}
transmembrane domain {338-358}
exoplasmic loop {359-368}
transmembrane domain {369-389}
cytoplasmic loop {390-395}
transmembrane domain {396-416}
exoplasmic loop {417-425}
transmembrane domain {426-446}
cytoplasmic loop {447-455}
transmembrane domain {456-475}
exoplasmic loop {476-484}
transmembrane domain {485-505}
cytoplasmic domain {506-563}
Database Correlations
OMIM 607582
UniProt Q4U2R8
Pfam PF07690
Kegg hsa:9356
References
UniProt :accession Q4U2R8