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Protein

Solute carrier family 22 member 6

Gene

Slc22a6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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
  • urate transmembrane transporter activity Source: GO_Central

GO - Biological processi

  • alpha-ketoglutarate transport Source: UniProtKB
  • anion transport Source: RGD
  • 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
  • urate transport Source: GO_Central

Enzyme and pathway databases

ReactomeiR-RNO-561048 Organic anion transport
SABIO-RKiO35956

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi69338 Slc22a6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi56N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi113N-linked (GlcNAc...) asparagineSequence 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

BioGridi248147, 1 interactor
IntActiO35956, 1 interactor
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
OMAiRWYSSSG
OrthoDBiEOG091G07CO
PhylomeDBiO35956
TreeFamiTF315847

Family and domain databases

CDDicd06174 MFS, 1 hit
InterProiView protein in InterPro
IPR020846 MFS_dom
IPR005828 MFS_sugar_transport-like
IPR036259 MFS_trans_sf
IPR004749 Orgcat_transp/SVOP
PfamiView protein in Pfam
PF00083 Sugar_tr, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit
TIGRFAMsiTIGR00898 2A0119, 1 hit
PROSITEiView protein in PROSITE
PS50850 MFS, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiS22A6_RAT
AccessioniPrimary (citable) accession number: O35956
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: April 25, 2018
This is version 127 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health