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Q8VC69 (S22A6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Slc22a6
Synonyms:Nkt, Oat1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length545 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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), 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. Ref.4 Ref.5 Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: Localized to the plasma membrane. Ref.1

Tissue specificity

Expressed in kidney; in the basolateral membrane and at much lower levels in brain. Ref.1 Ref.4

Developmental stage

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

Domain

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

Post-translational modification

Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane. Ref.7

Sequence similarities

Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]

Biophysicochemical properties

Kinetic parameters:

KM=37.3 µM for PAH Ref.4

Vmax=210 pmol/min/mg enzyme for PAH uptake

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processalpha-ketoglutarate transport

Inferred from sequence or structural similarity. Source: UniProtKB

anion transport

Inferred from direct assay PubMed 10751225. Source: MGI

organic anion transport

Inferred from mutant phenotype PubMed 22169006. Source: UniProtKB

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

renal tubular secretion

Inferred from mutant phenotype PubMed 22169006. Source: UniProtKB

response to methotrexate

Inferred from electronic annotation. Source: Ensembl

sodium-independent organic anion transport

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasolateral plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

caveola

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from direct assay Ref.7. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchloride ion binding

Inferred from electronic annotation. Source: Ensembl

inorganic anion exchanger activity

Inferred from sequence or structural similarity. Source: UniProtKB

organic anion transmembrane transporter activity

Inferred from mutant phenotype PubMed 22169006. Source: UniProtKB

sodium-independent organic anion transmembrane transporter activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 545545Solute carrier family 22 member 6
PRO_0000324168

Regions

Topological domain1 – 99Cytoplasmic Potential
Transmembrane10 – 3021Helical; Potential
Topological domain31 – 12999Extracellular Potential
Transmembrane130 – 15021Helical; Potential
Topological domain151 – 1577Cytoplasmic Potential
Transmembrane158 – 17720Helical; Potential
Topological domain178 – 1803Extracellular Potential
Transmembrane181 – 20121Helical; Potential
Topological domain202 – 21817Cytoplasmic Potential
Transmembrane219 – 23921Helical; Potential
Topological domain240 – 2423Extracellular Potential
Transmembrane243 – 26321Helical; Potential
Topological domain264 – 33168Cytoplasmic Potential
Transmembrane332 – 35221Helical; Potential
Topological domain353 – 36210Extracellular Potential
Transmembrane363 – 38321Helical; Potential
Topological domain384 – 3896Cytoplasmic Potential
Transmembrane390 – 41021Helical; Potential
Topological domain411 – 4199Extracellular Potential
Transmembrane420 – 44021Helical; Potential
Topological domain441 – 45010Cytoplasmic Potential
Transmembrane451 – 47121Helical; Potential
Topological domain472 – 4787Extracellular Potential
Transmembrane479 – 49921Helical; Potential
Topological domain500 – 54546Cytoplasmic Potential

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) Potential
Glycosylation561N-linked (GlcNAc...) Ref.7
Glycosylation861N-linked (GlcNAc...) Ref.7
Glycosylation911N-linked (GlcNAc...) Ref.7
Glycosylation1071N-linked (GlcNAc...) Ref.7
Glycosylation1781N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis391N → Q: Complete loss of PAH transport activity. Ref.7
Mutagenesis491C → 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. Ref.1
Mutagenesis1221C → 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. Ref.1
Mutagenesis1831C → 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. Ref.1
Mutagenesis4341C → 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. Ref.1
Sequence conflict661W → R in AAC53112. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8VC69 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 827782E115705C77

FASTA54560,013
        10         20         30         40         50         60 
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPAHHCR PPANANLSKD 

        70         80         90        100        110        120 
GGLEAWLPLD KQGRPESCLR FPFPHNGTEA NGTGVTEPCL DGWVYDNSTF PSTIVTEWNL 

       130        140        150        160        170        180 
VCSHRAFRQL AQSLFMVGVL LGAMMFGYLA DRLGRRKVLI LNYLQTAVSG TCAAYAPNYT 

       190        200        210        220        230        240 
VYCIFRLLSG MSLASIAINC MTLNMEWMPI HTRAYVGTLI GYVYSLGQFL LAGIAYAVPH 

       250        260        270        280        290        300 
WRHLQLAVSV PFFVAFIYSW FFIESARWYS SSGRLDLTLR ALQRVARING KQEEGAKLSI 

       310        320        330        340        350        360 
EVLQTSLQKE LTLNKGQASA MELLRCPTLR RLFLCLSMLW FATSFAYYGL VMDLQGFGVS 

       370        380        390        400        410        420 
MYLIQVIFGA VDLPAKFVCF LVINSMGRRP AQLASLLLAG ICILVNGIIP RGHTIIRTSL 

       430        440        450        460        470        480 
AVLGKGCLAS SFNCIFLYTG ELYPTMIRQT GLGMGSTMAR VGSIVSPLIS MTAEFYPSIP 

       490        500        510        520        530        540 
LFIFGAVPVA ASAVTALLPE TLGQPLPDTV QDLKSRSRGK QKQQQLEQQK QMIPLQVSTQ 


EKNGL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of NKT, a gene product related to the organic cation transporter family that is almost exclusively expressed in the kidney."
Lopez-Nieto C.E., You G., Bush K.T., Barros E.J., Beier D.R., Nigam S.K.
J. Biol. Chem. 272:6471-6478(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, MUTAGENESIS OF CYS-49; CYS-78; CYS-99; CYS-122; CYS-172; CYS-183; CYS-200; CYS-326; CYS-335; CYS-379; CYS-402; CYS-427 AND CYS-434, SUBCELLULAR LOCATION.
Strain: BALB/c.
Tissue: Kidney.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Cerebellum.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Liver.
[4]"Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells."
Kuze K., Graves P., Leahy A., Wilson P., Stuhlmann H., You G.
J. Biol. Chem. 274:1519-1524(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[5]"Regulation of mOAT-mediated organic anion transport by okadaic acid and protein kinase C in LLC-PK(1) cells."
You G., Kuze K., Kohanski R.A., Amsler K., Henderson S.
J. Biol. Chem. 275:10278-10284(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Cysteine residues in the organic anion transporter mOAT1."
Tanaka K., Zhou F., Kuze K., You G.
Biochem. J. 380:283-287(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Role of glycosylation in the organic anion transporter OAT1."
Tanaka K., Xu W., Zhou F., You G.
J. Biol. Chem. 279:14961-14966(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASN-39, GLYCOSYLATION AT ASN-56; ASN-86; ASN-91 AND ASN-107.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U52842 mRNA. Translation: AAC53112.1.
AK035971 mRNA. Translation: BAC29261.1.
BC021647 mRNA. Translation: AAH21647.1.
CCDSCCDS29538.1.
RefSeqNP_032792.2. NM_008766.3.
UniGeneMm.30090.

3D structure databases

ProteinModelPortalQ8VC69.
SMRQ8VC69. Positions 133-503.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ8VC69.
ChEMBLCHEMBL5653.

Proteomic databases

MaxQBQ8VC69.
PaxDbQ8VC69.
PRIDEQ8VC69.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000010250; ENSMUSP00000010250; ENSMUSG00000024650.
GeneID18399.
KEGGmmu:18399.
UCSCuc008gme.2. mouse.

Organism-specific databases

CTD9356.
MGIMGI:892001. Slc22a6.

Phylogenomic databases

eggNOGCOG0477.
GeneTreeENSGT00750000117345.
HOGENOMHOG000234569.
HOVERGENHBG108433.
InParanoidQ8VC69.
KOK08203.
OMAMIRQTGM.
OrthoDBEOG7C8GH9.
PhylomeDBQ8VC69.
TreeFamTF315847.

Gene expression databases

BgeeQ8VC69.
GenevestigatorQ8VC69.

Family and domain databases

InterProIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[Graphical view]
PfamPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
TIGRFAMsTIGR00898. 2A0119. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC22A6. mouse.
NextBio294008.
PROQ8VC69.
SOURCESearch...

Entry information

Entry nameS22A6_MOUSE
AccessionPrimary (citable) accession number: Q8VC69
Secondary accession number(s): Q61185
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2002
Last modified: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot