Search by BoMiProt ID - Bomi9319


Primary Information

BoMiProt ID Bomi9319
Protein Name Solute carrier family 22 member 6/Organic anion transporter 1 Renal organic anion transporter 1/ROAT1
Organism Bos taurus
Uniprot IdQ864Z3
Milk FractionWhey
Ref Sequence Id NP_001001143.1
Aminoacid Length 549
Molecular Weight 60184
Fasta Sequence https://www.uniprot.org/uniprot/Q864Z3.fasta
Gene Name SLC22A6/OAT1
Gene Id 407180
Protein Existence Status reviewed

Secondary Information

Protein Function Acts as an organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc).Responsible for removal of endogenous and exogenous organic anions at kidney level.
Biochemical Properties tend to have 12 transmembrane domains.Contain multiple glycosylation sites,PKC phosphorylation sites.utilize a tertiarytransport mechanism to move organic anions/drugs across the basolateralmembrane into the proximal tubule cells for subsequent exit across the apical membrane into the urine for elimination. This tertiarytransport mechanism involves three transport systems: Na+/K+-ATPase actively pumps Na+ out of the proximal tubule cells, establishing an inwardly directed (blood to cell) Na+ gradient. The potential energy stored in this Na+ gradient is used by a second transport protein, Na+/dicarboxylate cotransporter (SDCT2), to import the dicarboxylate α-ketoglutarate (α-KG), maintaining an outwardly directed (cell to blood) α-KG gradient. α-KG then serves as the physiological counterion for the third transport protein in this chain, a dicarboxylate/organic anion exchanger, namely OAT, which translocates organic anion substrates into the cells.Once inside cells, the organic anions then move across the apical membrane into the urine for secretion via other transporters.
PTMs Phosphorylation,Ubl conjugation,Glycosylation
Significance of PTMs organic anion transporter 1 is phosphorylated by PKC which is associated with the endocytosis and trafficking of internalized transporters.Structural motif (L/P)PxY on OAT1 is signaled for Nedd4-2 ubiquitination by PKC, resulting in the internalization of the transporters and a consequential decrease in their function.Overexpression of Nedd4-1 or Nedd4-2 enhanced OAT1 ubiquitination, reduced OAT1 expression at the cell surface, and suppressed OAT1 transport activity.Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane
Linking IDs Bomi9319
Bibliography 1.Xu D, Wang H, You G. Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel. Med Res Rev. 2016 Sep;36(5):964-79. doi: 10.1002/med.21397. Epub 2016 Jun 12. PMID: 27291023; PMCID: PMC5147025. 2.Czuba, L. C., Hillgren, K. M., & Swaan, P. W. (2018). Post-translational modifications of transporters. Pharmacology & therapeutics, 192, 88–99. https://doi.org/10.1016/j.pharmthera.2018.06.013
Protein Function Acts as an organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc).Responsible for removal of endogenous and exogenous organic anions at kidney level.
Biochemical Properties tend to have 12 transmembrane domains.Contain multiple glycosylation sites,PKC phosphorylation sites.utilize a tertiarytransport mechanism to move organic anions/drugs across the basolateralmembrane into the proximal tubule cells for subsequent exit across the apical membrane into the urine for elimination. This tertiarytransport mechanism involves three transport systems: Na+/K+-ATPase actively pumps Na+ out of the proximal tubule cells, establishing an inwardly directed (blood to cell) Na+ gradient. The potential energy stored in this Na+ gradient is used by a second transport protein, Na+/dicarboxylate cotransporter (SDCT2), to import the dicarboxylate α-ketoglutarate (α-KG), maintaining an outwardly directed (cell to blood) α-KG gradient. α-KG then serves as the physiological counterion for the third transport protein in this chain, a dicarboxylate/organic anion exchanger, namely OAT, which translocates organic anion substrates into the cells.Once inside cells, the organic anions then move across the apical membrane into the urine for secretion via other transporters.
PTMs Phosphorylation,Ubl conjugation,Glycosylation
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Phosphorylation
>sp|Q864Z3|S22A6_BOVIN Solute carrier family 22 member 6 OS=Bos taurus OX=9913 GN=SLC22A6 PE=2 SV=2 MAFNDLLLQLGGVGRFQKIQVTLVILPLILLASHNTLQNFTAAIPTHHCRPPADTN*56LSED GDLEAWLPRDGQGRPESCLLFTSPQRGPPFPN*92GTETNGTGATEPCPHGWIYDN*113STFPSTI VTEWDLVCSHRALRQLAQSLYMMGVLLGAMTFGCLADRLGRRKVLIFNYLQTAVSGTCAA FAPNFPAYCAFRFLSGMSTAGVVLNCMTLNVEWMPIHTRAYVGTLTGYVYSLGQFLLAGM AYAVPHWRYLQLLVSAPFFAFFIYSWFFIESARWYASSGRLDLTLRNLQRVAWINGKQEE GANLSMEALQASLKKELTTGKSQASALELIRCPALRRLFLCLSMLWFATSFAYYGLVMDL QGFGVSIYLIQVIFGAVDLPAKLVSFLVINNVGRRPAQMASLLLAGICILINGVVPKDKS IVRTSLAVLGKGCLASSFNCIFLYTGEVYPTMIRQTGLGMGSTLARVGSIVSPLVSMTAE LYPSVPLFIYGAVPVAASAAIALLPETLGQPLPDTVQDVENRRRGKTRKQQEELQKQMVP LQASAQVKN
Predicted Disorder Regions 52-73, 86-103, 518-549
DisProt Annotation
TM Helix Prediction 9 TMHs; (19-37), (164-182), (191-213), (220-242), (251-269), (338-356), (368-390), (397-415), (424-446)
Significance of PTMs organic anion transporter 1 is phosphorylated by PKC which is associated with the endocytosis and trafficking of internalized transporters.Structural motif (L/P)PxY on OAT1 is signaled for Nedd4-2 ubiquitination by PKC, resulting in the internalization of the transporters and a consequential decrease in their function.Overexpression of Nedd4-1 or Nedd4-2 enhanced OAT1 ubiquitination, reduced OAT1 expression at the cell surface, and suppressed OAT1 transport activity.Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane
Linking IDs
Bibliography 1.Xu D, Wang H, You G. Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel. Med Res Rev. 2016 Sep;36(5):964-79. doi: 10.1002/med.21397. Epub 2016 Jun 12. PMID: 27291023; PMCID: PMC5147025. 2.Czuba, L. C., Hillgren, K. M., & Swaan, P. W. (2018). Post-translational modifications of transporters. Pharmacology & therapeutics, 192, 88–99. https://doi.org/10.1016/j.pharmthera.2018.06.013