Details of Protein

General Information of Protein (ID: PRT00710)
Name Organic anion transporter 1 (OAT1)
Synonyms   Click to Show/Hide Synonyms of This Protein
Organic anion transporter 1; hOAT1; PAH transporter; hPAHT; Renal organic anion transporter 1; hROAT1; SLC22A6; OAT1; PAHT
Gene Name SLC22A6 Gene ID
9356
UniProt ID
Q4U2R8
Family Organic ion transporter (OIT)
TC Number   TC: 2.A.1.19.31  (Click to Show/Hide the Complete TC Tree)
The Major Facilitator Superfamily (MFS)
The Organic Cation Transporter (OCT) Family (The SLC22A family including OCT1-3, OCTN1-3 and OAT1-5 of H. sapiens)
TC: 2.A.1.19.31
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MAFNDLLQQVGGVGRFQQIQVTLVVLPLLLMASHNTLQNFTAAIPTHHCRPPADANLSKN
GGLEVWLPRDRQGQPESCLRFTSPQWGLPFLNGTEANGTGATEPCTDGWIYDNSTFPSTI
VTEWDLVCSHRALRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAA
FAPNFPIYCAFRLLSGMALAGISLNCMTLNVEWMPIHTRACVGTLIGYVYSLGQFLLAGV
AYAVPHWRHLQLLVSAPFFAFFIYSWFFIESARWHSSSGRLDLTLRALQRVARINGKREE
GAKLSMEVLRASLQKELTMGKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDL
QGFGVSIYLIQVIFGAVDLPAKLVGFLVINSLGRRPAQMAALLLAGICILLNGVIPQDQS
IVRTSLAVLGKGCLAASFNCIFLYTGELYPTMIRQTGMGMGSTMARVGSIVSPLVSMTAE
LYPSMPLFIYGAVPVAASAVTVLLPETLGQPLPDTVQDLESRWAPTQKEAGIYPRKGKQT
RQQQEHQKYMVPLQASAQEKNGL
Function Involved in the renal elimination of endogenous and exogenous organic anions. Functions as 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). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-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) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Benzenoids
            4-Aminohippuric acid Click to Show/Hide the Full List of Regulating Pair(s):   7 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (F438Y) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease (FC = 0.30)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (F438Y) of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (K431R) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease (FC = 0.30)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (K431R) of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Furosemide) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Indomethacin) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Probenecid) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (6) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Steviol) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
               Regulating Pair (7) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Unlabeled Para-aminohippurate (PAH)) of SLC22A6
                      Induced Change 4-Aminohippuric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC22A6 leads to the decrease of 4-aminohippuric acid levels compared with control group.
      Organoheterocyclic compounds
            Cidofovir Click to Show/Hide the Full List of Regulating Pair(s):   6 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (F438A) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (F438A) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (F438Y) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (F438Y) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (K431A) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (K431A) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (K431R) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (K431R) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (Y230A) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (Y230A) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
               Regulating Pair (6) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (Y230F) of SLC22A6
                      Induced Change Cidofovir concentration: decrease (FC = 0.25)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (Y230F) of SLC22A6 leads to the decrease of cidofovir levels compared with control group.
      Phenylpropanoids and polyketides
            Tetracycline Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Overexpression of SLC22A6
                      Induced Change Tetracycline concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC22A6 leads to the increase of tetracycline levels compared with control group.
References
1 A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport. J Biol Chem. 2006 Dec 8;281(49):38071-9.
2 Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). J Pharmacol Exp Ther. 2005 May;313(2):621-8.
3 Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.

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