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Q8VC69

- S22A6_MOUSE

UniProt

Q8VC69 - S22A6_MOUSE

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Protein
Solute carrier family 22 member 6
Gene
Slc22a6, Nkt, Oat1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.3 Publications

Kineticsi

  1. KM=37.3 µM for PAH1 Publication

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

GO - Molecular functioni

  1. chloride ion binding Source: Ensembl
  2. inorganic anion exchanger activity Source: UniProtKB
  3. organic anion transmembrane transporter activity Source: UniProtKB
  4. sodium-independent organic anion transmembrane transporter activity Source: Ensembl
Complete GO annotation...

GO - Biological processi

  1. alpha-ketoglutarate transport Source: UniProtKB
  2. anion transport Source: MGI
  3. organic anion transport Source: UniProtKB
  4. protein homooligomerization Source: Ensembl
  5. renal tubular secretion Source: UniProtKB
  6. response to methotrexate Source: Ensembl
  7. sodium-independent organic anion transport Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_198604. 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
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:892001. Slc22a6.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 99Cytoplasmic Reviewed prediction
Transmembranei10 – 3021Helical; Reviewed prediction
Add
BLAST
Topological domaini31 – 12999Extracellular Reviewed prediction
Add
BLAST
Transmembranei130 – 15021Helical; Reviewed prediction
Add
BLAST
Topological domaini151 – 1577Cytoplasmic Reviewed prediction
Transmembranei158 – 17720Helical; Reviewed prediction
Add
BLAST
Topological domaini178 – 1803Extracellular Reviewed prediction
Transmembranei181 – 20121Helical; Reviewed prediction
Add
BLAST
Topological domaini202 – 21817Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei219 – 23921Helical; Reviewed prediction
Add
BLAST
Topological domaini240 – 2423Extracellular Reviewed prediction
Transmembranei243 – 26321Helical; Reviewed prediction
Add
BLAST
Topological domaini264 – 33168Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei332 – 35221Helical; Reviewed prediction
Add
BLAST
Topological domaini353 – 36210Extracellular Reviewed prediction
Transmembranei363 – 38321Helical; Reviewed prediction
Add
BLAST
Topological domaini384 – 3896Cytoplasmic Reviewed prediction
Transmembranei390 – 41021Helical; Reviewed prediction
Add
BLAST
Topological domaini411 – 4199Extracellular Reviewed prediction
Transmembranei420 – 44021Helical; Reviewed prediction
Add
BLAST
Topological domaini441 – 45010Cytoplasmic Reviewed prediction
Transmembranei451 – 47121Helical; Reviewed prediction
Add
BLAST
Topological domaini472 – 4787Extracellular Reviewed prediction
Transmembranei479 – 49921Helical; Reviewed prediction
Add
BLAST
Topological domaini500 – 54546Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. basolateral plasma membrane Source: UniProtKB
  2. caveola Source: Ensembl
  3. integral component of plasma membrane Source: UniProtKB
  4. protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391N → Q: Complete loss of PAH transport activity. 1 Publication
Mutagenesisi49 – 491C → 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 Publication
Mutagenesisi122 – 1221C → 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 Publication
Mutagenesisi183 – 1831C → 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 Publication
Mutagenesisi434 – 4341C → 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 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 545545Solute carrier family 22 member 6
PRO_0000324168Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi39 – 391N-linked (GlcNAc...) Reviewed prediction
Glycosylationi56 – 561N-linked (GlcNAc...)1 Publication
Glycosylationi86 – 861N-linked (GlcNAc...)1 Publication
Glycosylationi91 – 911N-linked (GlcNAc...)1 Publication
Glycosylationi107 – 1071N-linked (GlcNAc...)1 Publication
Glycosylationi178 – 1781N-linked (GlcNAc...) Reviewed prediction

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.

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

BgeeiQ8VC69.
GenevestigatoriQ8VC69.

Interactioni

Structurei

3D structure databases

ProteinModelPortaliQ8VC69.
SMRiQ8VC69. Positions 133-503.

Family & Domainsi

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0477.
GeneTreeiENSGT00750000117345.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiQ8VC69.
KOiK08203.
OMAiMIRQTGM.
OrthoDBiEOG7C8GH9.
PhylomeDBiQ8VC69.
TreeFamiTF315847.

Family and domain databases

InterProiIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[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

MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPAHHCR    50
PPANANLSKD GGLEAWLPLD KQGRPESCLR FPFPHNGTEA NGTGVTEPCL 100
DGWVYDNSTF PSTIVTEWNL VCSHRAFRQL AQSLFMVGVL LGAMMFGYLA 150
DRLGRRKVLI LNYLQTAVSG TCAAYAPNYT VYCIFRLLSG MSLASIAINC 200
MTLNMEWMPI HTRAYVGTLI GYVYSLGQFL LAGIAYAVPH WRHLQLAVSV 250
PFFVAFIYSW FFIESARWYS SSGRLDLTLR ALQRVARING KQEEGAKLSI 300
EVLQTSLQKE LTLNKGQASA MELLRCPTLR RLFLCLSMLW FATSFAYYGL 350
VMDLQGFGVS MYLIQVIFGA VDLPAKFVCF LVINSMGRRP AQLASLLLAG 400
ICILVNGIIP RGHTIIRTSL AVLGKGCLAS SFNCIFLYTG ELYPTMIRQT 450
GLGMGSTMAR VGSIVSPLIS MTAEFYPSIP LFIFGAVPVA ASAVTALLPE 500
TLGQPLPDTV QDLKSRSRGK QKQQQLEQQK QMIPLQVSTQ EKNGL 545
Length:545
Mass (Da):60,013
Last modified:March 1, 2002 - v1
Checksum:i827782E115705C77
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661W → R in AAC53112. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U52842 mRNA. Translation: AAC53112.1 .
AK035971 mRNA. Translation: BAC29261.1 .
BC021647 mRNA. Translation: AAH21647.1 .
CCDSi CCDS29538.1.
RefSeqi NP_032792.2. NM_008766.3.
UniGenei Mm.30090.

3D structure databases

ProteinModelPortali Q8VC69.
SMRi Q8VC69. Positions 133-503.
ModBasei Search...

Chemistry

BindingDBi Q8VC69.
ChEMBLi CHEMBL5653.

Proteomic databases

MaxQBi Q8VC69.
PaxDbi Q8VC69.
PRIDEi Q8VC69.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000010250 ; ENSMUSP00000010250 ; ENSMUSG00000024650 .
GeneIDi 18399.
KEGGi mmu:18399.
UCSCi uc008gme.2. mouse.

Organism-specific databases

CTDi 9356.
MGIi MGI:892001. Slc22a6.

Phylogenomic databases

eggNOGi COG0477.
GeneTreei ENSGT00750000117345.
HOGENOMi HOG000234569.
HOVERGENi HBG108433.
InParanoidi Q8VC69.
KOi K08203.
OMAi MIRQTGM.
OrthoDBi EOG7C8GH9.
PhylomeDBi Q8VC69.
TreeFami TF315847.

Enzyme and pathway databases

Reactomei REACT_198604. Organic anion transport.

Miscellaneous databases

ChiTaRSi SLC22A6. mouse.
NextBioi 294008.
PROi Q8VC69.
SOURCEi Search...

Gene expression databases

Bgeei Q8VC69.
Genevestigatori Q8VC69.

Family and domain databases

InterProi IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[Graphical view ]
Pfami PF00083. Sugar_tr. 1 hit.
[Graphical view ]
SUPFAMi SSF103473. SSF103473. 1 hit.
TIGRFAMsi TIGR00898. 2A0119. 1 hit.
PROSITEi PS50850. MFS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

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: September 3, 2014
This is version 105 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

External Data

Dasty 3

Similar proteinsi