Solute carrier family 22 member 6 - Mus musculus (Mouse)

Preferred order of sections

Names and origin

Protein names

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 names

Name:	Slc22a6
Synonyms:	Nkt, Oat1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	545 AA.
Sequence status	Complete.
Protein existence	Evidence 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: K_M=37.3 µM for PAH Ref.4 V_max=210 pmol/min/mg enzyme for PAH uptake

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	alpha-ketoglutarate transport Inferred from sequence or structural similarity. Source: UniProtKB renal tubular secretion Inferred from mutant phenotype PubMed 22169006. Source: UniProtKB response to methotrexate Inferred from electronic annotation. Source: Compara sodium-independent organic anion transport Inferred from electronic annotation. Source: Compara
Cellular_component	basolateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB caveola Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	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: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 545

545

Solute carrier family 22 member 6

PRO_0000324168

Regions

Topological domain

1 – 9

9

Cytoplasmic Potential

Transmembrane

10 – 30

21

Helical; Potential

Topological domain

31 – 129

99

Extracellular Potential

Transmembrane

130 – 150

21

Helical; Potential

Topological domain

151 – 157

7

Cytoplasmic Potential

Transmembrane

158 – 177

20

Helical; Potential

Topological domain

178 – 180

3

Extracellular Potential

Transmembrane

181 – 201

21

Helical; Potential

Topological domain

202 – 218

17

Cytoplasmic Potential

Transmembrane

219 – 239

21

Helical; Potential

Topological domain

240 – 242

3

Extracellular Potential

Transmembrane

243 – 263

21

Helical; Potential

Topological domain

264 – 331

68

Cytoplasmic Potential

Transmembrane

332 – 352

21

Helical; Potential

Topological domain

353 – 362

10

Extracellular Potential

Transmembrane

363 – 383

21

Helical; Potential

Topological domain

384 – 389

6

Cytoplasmic Potential

Transmembrane

390 – 410

21

Helical; Potential

Topological domain

411 – 419

9

Extracellular Potential

Transmembrane

420 – 440

21

Helical; Potential

Topological domain

441 – 450

10

Cytoplasmic Potential

Transmembrane

451 – 471

21

Helical; Potential

Topological domain

472 – 478

7

Extracellular Potential

Transmembrane

479 – 499

21

Helical; Potential

Topological domain

500 – 545

46

Cytoplasmic Potential

Amino acid modifications

Glycosylation

39

1

N-linked (GlcNAc...) Potential

Glycosylation

56

1

N-linked (GlcNAc...) Ref.7

Glycosylation

86

1

N-linked (GlcNAc...) Ref.7

Glycosylation

91

1

N-linked (GlcNAc...) Ref.7

Glycosylation

107

1

N-linked (GlcNAc...) Ref.7

Glycosylation

178

1

N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis

39

1

N → Q: Complete loss of PAH transport activity. Ref.7

Mutagenesis

49

1

C → 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

Mutagenesis

122

1

C → 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

Mutagenesis

183

1

C → 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

Mutagenesis

434

1

C → 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 conflict

66

1

W → R in AAC53112. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q8VC69 [UniParc].

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

FASTA

545

60,013

        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' referencesShow '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. 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.
IPI	IPI00310736.
RefSeq	NP_032792.2. NM_008766.3.
UniGene	Mm.30090.
3D structure databases
ProteinModelPortal	Q8VC69.
ModBase	Search...
Proteomic databases
PaxDb	Q8VC69.
PRIDE	Q8VC69.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000010250; ENSMUSP00000010250; ENSMUSG00000024650.
GeneID	18399.
KEGG	mmu:18399.
UCSC	uc008gme.2. mouse.
Organism-specific databases
CTD	9356.
MGI	MGI:892001. Slc22a6.
Phylogenomic databases
eggNOG	COG0477.
GeneTree	ENSGT00550000074177.
HOGENOM	HOG000234569.
HOVERGEN	HBG108433.
InParanoid	Q8VC69.
KO	K08203.
OMA	APFFAFF.
OrthoDB	EOG418BPG.
Gene expression databases
Bgee	Q8VC69.
Genevestigator	Q8VC69.
Family and domain databases
InterPro	IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004749. Orgcat_transp. IPR005828. Sub_transporter. [Graphical view]
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00898. 2A0119. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8VC69.
ChEMBL	CHEMBL5653.
ChiTaRS	SLC22A6. mouse.
NextBio	294008.
SOURCE	Search...

Entry information

Entry name

S22A6_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents