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Protein

Solute carrier family 22 member 6

Gene

Slc22a6

Organism
Mus musculus (Mouse)
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), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP), 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) and edaravone sulfate (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH). 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, bumetamide, losartan, probenecid, phenol red, urate, glutarate and alpha-ketoglutarate (By similarity). PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), indomethacin, sulindac, diclofenac, carprofen, okadaic acid and PKC activators.By similarity3 Publications

Kineticsi

  1. KM=37.3 µM for PAH1 Publication
  1. Vmax=210 pmol/min/mg enzyme for PAH uptake1 Publication

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-MMU-561048. Organic anion transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 6
Alternative name(s):
Kidney-specific transport protein
Novel kidney transcript
Short name:
mNKT
Organic anion transporter 1
Renal organic anion transporter 1
Short name:
mROAT1
Gene namesi
Name:Slc22a6
Synonyms:Nkt, Oat1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:892001. Slc22a6.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

  • Note: Localized to the plasma membrane.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9CytoplasmicSequence analysis9
Transmembranei10 – 30HelicalSequence analysisAdd BLAST21
Topological domaini31 – 129ExtracellularSequence analysisAdd BLAST99
Transmembranei130 – 150HelicalSequence analysisAdd BLAST21
Topological domaini151 – 157CytoplasmicSequence analysis7
Transmembranei158 – 177HelicalSequence analysisAdd BLAST20
Topological domaini178 – 180ExtracellularSequence analysis3
Transmembranei181 – 201HelicalSequence analysisAdd BLAST21
Topological domaini202 – 218CytoplasmicSequence analysisAdd BLAST17
Transmembranei219 – 239HelicalSequence analysisAdd BLAST21
Topological domaini240 – 242ExtracellularSequence analysis3
Transmembranei243 – 263HelicalSequence analysisAdd BLAST21
Topological domaini264 – 331CytoplasmicSequence analysisAdd BLAST68
Transmembranei332 – 352HelicalSequence analysisAdd BLAST21
Topological domaini353 – 362ExtracellularSequence analysis10
Transmembranei363 – 383HelicalSequence analysisAdd BLAST21
Topological domaini384 – 389CytoplasmicSequence analysis6
Transmembranei390 – 410HelicalSequence analysisAdd BLAST21
Topological domaini411 – 419ExtracellularSequence analysis9
Transmembranei420 – 440HelicalSequence analysisAdd BLAST21
Topological domaini441 – 450CytoplasmicSequence analysis10
Transmembranei451 – 471HelicalSequence analysisAdd BLAST21
Topological domaini472 – 478ExtracellularSequence analysis7
Transmembranei479 – 499HelicalSequence analysisAdd BLAST21
Topological domaini500 – 545CytoplasmicSequence analysisAdd BLAST46

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39N → Q: Complete loss of PAH transport activity. 1 Publication1
Mutagenesisi49C → A: Decrease in the level of cell surface expression and transport function. Complete loss of transport function; when associated with A-78; A-99; A-122; A-172; A-183; A-200; A-362; A-335; A-379; A-402; A-427 and A-434. 1 Publication1
Mutagenesisi122C → A: Decrease in the level of cell surface expression and transport function. Complete loss of transport function; when associated with A-49; A-78; A-99; A-172; A-183; A-200; A-362; A-335; A-379; A-402; A-427 and A-434. 1 Publication1
Mutagenesisi183C → A: Decrease in the level of cell surface expression and transport function. Complete loss of transport function; when associated with A-49; A-78; A-99; A-122; A-172; A-200; A-362; A-335; A-379; A-402; A-427 and A-434. 1 Publication1
Mutagenesisi434C → A: Decrease in the level of cell surface expression and transport function. 80% decrease in the level of transport activity; when associated with A-49; A-122 and A-183. Complete loss of transport function; when associated with A-49; A-78; A-99; A-122; A-172; A-183; A-200; A-362; A-335; A-379; A-402 and A-427. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003241681 – 545Solute carrier family 22 member 6Add BLAST545

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...)Sequence analysis1
Glycosylationi56N-linked (GlcNAc...)1 Publication1
Glycosylationi86N-linked (GlcNAc...)1 Publication1
Glycosylationi91N-linked (GlcNAc...)1 Publication1
Glycosylationi107N-linked (GlcNAc...)1 Publication1
Glycosylationi178N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ8VC69.
PaxDbiQ8VC69.
PRIDEiQ8VC69.

PTM databases

iPTMnetiQ8VC69.
PhosphoSitePlusiQ8VC69.

Expressioni

Tissue specificityi

Expressed in kidney; in the basolateral membrane and at much lower levels in brain.2 Publications

Developmental stagei

Developmentally regulated with significant expression beginning at E18 and rising just before birth.

Gene expression databases

BgeeiENSMUSG00000024650.
GenevisibleiQ8VC69. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000010250.

Chemistry databases

BindingDBiQ8VC69.

Structurei

3D structure databases

ProteinModelPortaliQ8VC69.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiQ8VC69.
KOiK08203.
OMAiHNGTEAN.
OrthoDBiEOG091G07CO.
PhylomeDBiQ8VC69.
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.

Q8VC69-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPAHHCR
60 70 80 90 100
PPANANLSKD GGLEAWLPLD KQGRPESCLR FPFPHNGTEA NGTGVTEPCL
110 120 130 140 150
DGWVYDNSTF PSTIVTEWNL VCSHRAFRQL AQSLFMVGVL LGAMMFGYLA
160 170 180 190 200
DRLGRRKVLI LNYLQTAVSG TCAAYAPNYT VYCIFRLLSG MSLASIAINC
210 220 230 240 250
MTLNMEWMPI HTRAYVGTLI GYVYSLGQFL LAGIAYAVPH WRHLQLAVSV
260 270 280 290 300
PFFVAFIYSW FFIESARWYS SSGRLDLTLR ALQRVARING KQEEGAKLSI
310 320 330 340 350
EVLQTSLQKE LTLNKGQASA MELLRCPTLR RLFLCLSMLW FATSFAYYGL
360 370 380 390 400
VMDLQGFGVS MYLIQVIFGA VDLPAKFVCF LVINSMGRRP AQLASLLLAG
410 420 430 440 450
ICILVNGIIP RGHTIIRTSL AVLGKGCLAS SFNCIFLYTG ELYPTMIRQT
460 470 480 490 500
GLGMGSTMAR VGSIVSPLIS MTAEFYPSIP LFIFGAVPVA ASAVTALLPE
510 520 530 540
TLGQPLPDTV QDLKSRSRGK QKQQQLEQQK QMIPLQVSTQ EKNGL
Length:545
Mass (Da):60,013
Last modified:March 1, 2002 - v1
Checksum:i827782E115705C77
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66W → R in AAC53112 (PubMed:9045672).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U52842 mRNA. Translation: AAC53112.1.
AK035971 mRNA. Translation: BAC29261.1.
BC021647 mRNA. Translation: AAH21647.1.
CCDSiCCDS29538.1.
RefSeqiNP_032792.2. NM_008766.3.
UniGeneiMm.30090.

Genome annotation databases

EnsembliENSMUST00000010250; ENSMUSP00000010250; ENSMUSG00000024650.
GeneIDi18399.
KEGGimmu:18399.
UCSCiuc008gme.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U52842 mRNA. Translation: AAC53112.1.
AK035971 mRNA. Translation: BAC29261.1.
BC021647 mRNA. Translation: AAH21647.1.
CCDSiCCDS29538.1.
RefSeqiNP_032792.2. NM_008766.3.
UniGeneiMm.30090.

3D structure databases

ProteinModelPortaliQ8VC69.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000010250.

Chemistry databases

BindingDBiQ8VC69.
ChEMBLiCHEMBL5653.

PTM databases

iPTMnetiQ8VC69.
PhosphoSitePlusiQ8VC69.

Proteomic databases

MaxQBiQ8VC69.
PaxDbiQ8VC69.
PRIDEiQ8VC69.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000010250; ENSMUSP00000010250; ENSMUSG00000024650.
GeneIDi18399.
KEGGimmu:18399.
UCSCiuc008gme.2. mouse.

Organism-specific databases

CTDi9356.
MGIiMGI:892001. Slc22a6.

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiQ8VC69.
KOiK08203.
OMAiHNGTEAN.
OrthoDBiEOG091G07CO.
PhylomeDBiQ8VC69.
TreeFamiTF315847.

Enzyme and pathway databases

ReactomeiR-MMU-561048. Organic anion transport.

Miscellaneous databases

ChiTaRSiSlc22a6. mouse.
PROiQ8VC69.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024650.
GenevisibleiQ8VC69. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q8VC69
Secondary accession number(s): Q61185
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2002
Last modified: November 30, 2016
This is version 125 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.