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Protein

Solute carrier family 22 member 6

Gene

Slc22a6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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), 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD) and edaravone sulfate. Mediates the sodium-independent uptake of p-aminohippurate (PAH), cidofovir, adefovir, 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF). PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), indomethacin, sulindac, diclofenac, carprofen, okadaic acid, benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, bumetamide, losartan, phenol red, urate and alpha-ketoglutarate (By similarity). PAH uptake is inhibited by glutarate and probenecid.By similarity2 Publications

Kineticsi

  1. KM=14.3 µM for PAH4 Publications
  2. KM=238 µM for cidofovir4 Publications
  3. KM=270 µM for adefovir4 Publications
  4. KM=10.2 µM for 2,4-D4 Publications
  5. KM=27.5 µM for HA4 Publications
  6. KM=47.1 µM for IA4 Publications
  7. KM=17.7 µM for IS4 Publications
  8. KM=154 µM for CMPF4 Publications
  1. Vmax=1270 pmol/min/mg enzyme for 2,4-D uptake4 Publications
  2. Vmax=519 pmol/min/mg enzyme for HA uptake4 Publications
  3. Vmax=387 pmol/min/mg enzyme for IA uptake4 Publications
  4. Vmax=350 pmol/min/mg enzyme for IS uptake4 Publications
  5. Vmax=1669 pmol/min/mg enzyme for CMPF uptake4 Publications

GO - Molecular functioni

  • anion:anion antiporter activity Source: RGD
  • chloride ion binding Source: RGD
  • inorganic anion exchanger activity Source: UniProtKB
  • organic anion transmembrane transporter activity Source: MGI
  • protein homodimerization activity Source: RGD
  • sodium-independent organic anion transmembrane transporter activity Source: RGD

GO - Biological processi

  • alpha-ketoglutarate transport Source: UniProtKB
  • organic anion transport Source: MGI
  • protein homooligomerization Source: RGD
  • renal tubular secretion Source: UniProtKB
  • response to methotrexate Source: RGD
  • sodium-independent organic anion transport Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-561048. Organic anion transport.

Protein family/group databases

TCDBi2.A.1.19.4. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 6
Alternative name(s):
Organic anion transporter 1
Short name:
rOAT1
renal organic anion transporter 1
Short name:
rROAT1
Gene namesi
Name:Slc22a6
Synonyms:Oat1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi69338. Slc22a6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9CytoplasmicSequence analysis9
Transmembranei10 – 30HelicalSequence analysisAdd BLAST21
Topological domaini31 – 135ExtracellularSequence analysisAdd BLAST105
Transmembranei136 – 156HelicalSequence analysisAdd BLAST21
Topological domaini157 – 164CytoplasmicSequence analysis8
Transmembranei165 – 187HelicalSequence analysisAdd BLAST23
Topological domaini188 – 195ExtracellularSequence analysis8
Transmembranei196 – 216HelicalSequence analysisAdd BLAST21
Topological domaini217 – 224CytoplasmicSequence analysis8
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 248ExtracellularSequence analysis3
Transmembranei249 – 269HelicalSequence analysisAdd BLAST21
Topological domaini270 – 337CytoplasmicSequence analysisAdd BLAST68
Transmembranei338 – 358HelicalSequence analysisAdd BLAST21
Topological domaini359 – 368ExtracellularSequence analysis10
Transmembranei369 – 389HelicalSequence analysisAdd BLAST21
Topological domaini390 – 395CytoplasmicSequence analysis6
Transmembranei396 – 416HelicalSequence analysisAdd BLAST21
Topological domaini417 – 425ExtracellularSequence analysis9
Transmembranei426 – 446HelicalSequence analysisAdd BLAST21
Topological domaini447 – 484CytoplasmicSequence analysisAdd BLAST38
Transmembranei485 – 505HelicalSequence analysisAdd BLAST21
Topological domaini506 – 551ExtracellularSequence analysisAdd BLAST46

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • caveola Source: RGD
  • extracellular exosome Source: Ensembl
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: RGD
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1777665.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003241711 – 551Solute carrier family 22 member 6Add BLAST551

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...)Sequence analysis1
Glycosylationi56N-linked (GlcNAc...)Sequence analysis1
Glycosylationi92N-linked (GlcNAc...)Sequence analysis1
Glycosylationi113N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane (By similarity).By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO35956.
PRIDEiO35956.

Expressioni

Tissue specificityi

Highly expressed in kidney; in the particular segment of the proximal tubule and to a lower extent in brain. Found preferentially in the cortex and outer medulla and weakly in the inner medulla.2 Publications

Inductioni

Down-regulated by PGE2 and in ischemic kidney.2 Publications

Gene expression databases

BgeeiENSRNOG00000018215.
GenevisibleiO35956. RN.

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

IntActiO35956. 1 interactor.
MINTiMINT-8292692.
STRINGi10116.ENSRNOP00000024756.

Chemistry databases

BindingDBiO35956.

Structurei

3D structure databases

ProteinModelPortaliO35956.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi527 – 537Poly-GlnAdd BLAST11

Domaini

Multiple cysteine residues are necessary for proper targeting to the plasma membrane.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiO35956.
KOiK08203.
OMAiMIRQTGM.
OrthoDBiEOG091G07CO.
PhylomeDBiO35956.
TreeFamiTF315847.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35956-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR
60 70 80 90 100
PPANANLSKD GGLEAWLPLD KQGQPESCLR FTSPQWGPPF YNGTEANGTR
110 120 130 140 150
VTEPCIDGWV YDNSTFPSTI VTEWNLVCSH RAFRQLAQSL YMVGVLLGAM
160 170 180 190 200
VFGYLADRLG RRKVLILNYL QTAVSGTCAA YAPNYTVYCV FRLLSGMSLA
210 220 230 240 250
SIAINCMTLN VEWMPIHTRA YVGTLIGYVY SLGQFLLAGI AYAVPHWRHL
260 270 280 290 300
QLVVSVPFFI AFIYSWFFIE SARWYSSSGR LDLTLRALQR VARINGKQEE
310 320 330 340 350
GAKLSIEVLR TSLQKELTLS KGQASAMELL RCPTLRHLFL CLSMLWFATS
360 370 380 390 400
FAYYGLVMDL QGFGVSMYLI QVIFGAVDLP AKFVCFLVIN SMGRRPAQMA
410 420 430 440 450
SLLLAGICIL VNGIIPKSHT IIRTSLAVLG KGCLASSFNC IFLYTGELYP
460 470 480 490 500
TVIRQTGLGM GSTMARVGSI VSPLVSMTAE FYPSMPLFIF GAVPVVASAV
510 520 530 540 550
TALLPETLGQ PLPDTVQDLK SRSRGKQNQQ QQEQQKQMMP LQASTQEKNG

L
Length:551
Mass (Da):60,766
Last modified:January 1, 1998 - v1
Checksum:i8BA47BE628324BF2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF008221 mRNA. Translation: AAC18772.1.
AB004559 mRNA. Translation: BAA22086.1.
BC104692 mRNA. Translation: AAI04693.1.
RefSeqiNP_058920.1. NM_017224.2.
UniGeneiRn.87849.

Genome annotation databases

EnsembliENSRNOT00000024757; ENSRNOP00000024756; ENSRNOG00000018215.
GeneIDi29509.
KEGGirno:29509.
UCSCiRGD:69338. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF008221 mRNA. Translation: AAC18772.1.
AB004559 mRNA. Translation: BAA22086.1.
BC104692 mRNA. Translation: AAI04693.1.
RefSeqiNP_058920.1. NM_017224.2.
UniGeneiRn.87849.

3D structure databases

ProteinModelPortaliO35956.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO35956. 1 interactor.
MINTiMINT-8292692.
STRINGi10116.ENSRNOP00000024756.

Chemistry databases

BindingDBiO35956.
ChEMBLiCHEMBL1777665.

Protein family/group databases

TCDBi2.A.1.19.4. the major facilitator superfamily (mfs).

Proteomic databases

PaxDbiO35956.
PRIDEiO35956.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000024757; ENSRNOP00000024756; ENSRNOG00000018215.
GeneIDi29509.
KEGGirno:29509.
UCSCiRGD:69338. rat.

Organism-specific databases

CTDi9356.
RGDi69338. Slc22a6.

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiO35956.
KOiK08203.
OMAiMIRQTGM.
OrthoDBiEOG091G07CO.
PhylomeDBiO35956.
TreeFamiTF315847.

Enzyme and pathway databases

ReactomeiR-RNO-561048. Organic anion transport.

Miscellaneous databases

PROiO35956.

Gene expression databases

BgeeiENSRNOG00000018215.
GenevisibleiO35956. RN.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS22A6_RAT
AccessioniPrimary (citable) accession number: O35956
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.