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Protein

Solute carrier family 22 member 6

Gene

SLC22A6

Organism
Homo sapiens (Human)
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) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), 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), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). 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, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.By similarity6 Publications

Kineticsi

  1. KM=9.3 µM for PAH (isoform 1)4 Publications
  2. KM=4 µM for PAH (isoform 2)4 Publications
  3. KM=11 µM for edaravone4 Publications
  4. KM=46 µM for cidofovir4 Publications
  5. KM=30 µM for adefovir4 Publications
  6. KM=5.77 µM for 2,4-D4 Publications
  7. KM=23.5 µM for HA4 Publications
  8. KM=14 µM for IA4 Publications
  9. KM=20.5 µM for IS4 Publications
  10. KM=141 µM for CMPF4 Publications
  1. Vmax=534 pmol/min/mg enzyme for 2,4-D uptake4 Publications
  2. Vmax=430 pmol/min/mg enzyme for HA uptake4 Publications
  3. Vmax=110 pmol/min/mg enzyme for IA uptake4 Publications
  4. Vmax=216 pmol/min/mg enzyme for IS uptake4 Publications
  5. Vmax=801 pmol/min/mg enzyme for CMPF uptake4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei230Important for interaction with cidofovir1
Sitei438Important for interaction with cidofovir and PAH1

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-HSA-561048. Organic anion transport.

Protein family/group databases

TCDBi2.A.1.19.31. 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:
hOAT1
PAH transporter
Short name:
hPAHT
Renal organic anion transporter 1
Short name:
hROAT1
Gene namesi
Name:SLC22A6
Synonyms:OAT1, PAHT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000197901.11.
HGNCiHGNC:10970. 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 – 190ExtracellularSequence analysis3
Transmembranei191 – 213HelicalSequence analysisAdd BLAST23
Topological domaini214 – 224CytoplasmicSequence analysisAdd BLAST11
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 – 455CytoplasmicSequence analysis9
Transmembranei456 – 475HelicalSequence analysisAdd BLAST20
Topological domaini476 – 484ExtracellularSequence analysis9
Transmembranei485 – 505HelicalSequence analysisAdd BLAST21
Topological domaini506 – 563CytoplasmicSequence analysisAdd BLAST58

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi30L → A: Complete loss of PAH transport activity. 1 Publication1
Mutagenesisi36T → A: Complete loss of PAH transport activity. 1 Publication1
Mutagenesisi39N → Q: Complete loss of PAH transport activity. 1 Publication1
Mutagenesisi230Y → A: Loss of membrane protein expression and little uptake of cidofovir. 1 Publication1
Mutagenesisi431K → A: Decrease in the level of membrane protein expression and 70 % loss of PAH uptake. 1 Publication1
Mutagenesisi438F → A: Decrease in the level of membrane protein expression, 70 % loss of PAH uptake, increased affinity for cidofovir, lower Vmax for PAH, and lower Km and Vmax for cidofovir. 1 Publication1

Organism-specific databases

DisGeNETi9356.
OpenTargetsiENSG00000197901.
PharmGKBiPA388.

Chemistry databases

ChEMBLiCHEMBL1641347.
DrugBankiDB00316. Acetaminophen.
DB00819. Acetazolamide.
DB06151. Acetylcysteine.
DB00945. Acetylsalicylic acid.
DB00787. Aciclovir.
DB00718. Adefovir Dipivoxil.
DB00345. Aminohippuric acid.
DB01424. Aminophenazone.
DB01060. Amoxicillin.
DB01435. Antipyrine.
DB00168. Aspartame.
DB01053. Benzylpenicillin.
DB01237. Bromodiphenhydramine.
DB00887. Bumetanide.
DB04519. Caprylic acid.
DB01197. Captopril.
DB00578. Carbenicillin.
DB00821. Carprofen.
DB00520. Caspofungin.
DB01414. Cefacetrile.
DB01140. Cefadroxil.
DB00456. Cefalotin.
DB01326. Cefamandole.
DB01327. Cefazolin.
DB01329. Cefoperazone.
DB00493. Cefotaxime.
DB00229. Cefotiam.
DB01333. Cefradine.
DB00438. Ceftazidime.
DB01212. Ceftriaxone.
DB00567. Cephalexin.
DB00446. Chloramphenicol.
DB00880. Chlorothiazide.
DB00672. Chlorpropamide.
DB00369. Cidofovir.
DB01597. Cilastatin.
DB00501. Cimetidine.
DB00827. Cinoxacin.
DB01147. Cloxacillin.
DB00286. Conjugated Equine Estrogens.
DB02527. Cyclic Adenosine Monophosphate.
DB02315. Cyclic Guanosine Monophosphate.
DB00091. Cyclosporine.
DB00606. Cyclothiazide.
DB08912. Dabrafenib.
DB04133. Degraded Cephaloridine.
DB00586. Diclofenac.
DB00900. Didanosine.
DB00861. Diflunisal.
DB01160. Dinoprost Tromethamine.
DB00917. Dinoprostone.
DB00254. Doxycycline.
DB08846. Ellagic Acid.
DB00584. Enalapril.
DB00903. Etacrynic acid.
DB00311. Ethoxzolamide.
DB00749. Etodolac.
DB02266. Flufenamic Acid.
DB00693. Fluorescein.
DB00712. Flurbiprofen.
DB00158. Folic Acid.
DB00529. Foscarnet.
DB00695. Furosemide.
DB01004. Ganciclovir.
DB00798. Gentamicin.
DB03553. Glutaric Acid.
DB01016. Glyburide.
DB00365. Grepafloxacin.
DB00999. Hydrochlorothiazide.
DB01050. Ibuprofen.
DB00328. Indomethacin.
DB01009. Ketoprofen.
DB00709. Lamivudine.
DB01137. Levofloxacin.
DB00678. Losartan.
DB00939. Meclofenamic acid.
DB00703. Methazolamide.
DB00563. Methotrexate.
DB01017. Minocycline.
DB00607. Nafcillin.
DB00779. Nalidixic Acid.
DB00788. Naproxen.
DB00731. Nateglinide.
DB01059. Norfloxacin.
DB01051. Novobiocin.
DB01165. Ofloxacin.
DB03585. Oxyphenbutazone.
DB00595. Oxytetracycline.
DB03783. Phenacetin.
DB00812. Phenylbutazone.
DB00319. Piperacillin.
DB00554. Piroxicam.
DB00175. Pravastatin.
DB01032. Probenecid.
DB00140. Riboflavin.
DB00936. Salicylic acid.
DB00649. Stavudine.
DB01082. Streptomycin.
DB00605. Sulindac.
DB04348. Taurocholic Acid.
DB00300. Tenofovir.
DB00759. Tetracycline.
DB01124. Tolbutamide.
DB00500. Tolmetin.
DB00432. Trifluridine.
DB08844. Uric Acid.
DB00577. Valaciclovir.
DB00313. Valproic Acid.
DB00512. Vancomycin.
DB00943. Zalcitabine.
DB00495. Zidovudine.
GuidetoPHARMACOLOGYi1025.

Polymorphism and mutation databases

BioMutaiSLC22A6.
DMDMi74762955.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003241661 – 563Solute carrier family 22 member 6Add BLAST563

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi56N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi92N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi97N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi113N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

Glycosylated. Glycosylation at Asn-113 may occur at a secondary level. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ4U2R8.
PaxDbiQ4U2R8.
PeptideAtlasiQ4U2R8.
PRIDEiQ4U2R8.

PTM databases

iPTMnetiQ4U2R8.
PhosphoSitePlusiQ4U2R8.

Expressioni

Tissue specificityi

Strongly expressed in kidney and to a lower extent in liver, skeletal muscle, brain and placenta. Found at the basolateral membrane of the proximal tubule.5 Publications

Gene expression databases

BgeeiENSG00000197901.
ExpressionAtlasiQ4U2R8. baseline and differential.
GenevisibleiQ4U2R8. HS.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926243EBI-749741,EBI-743771

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114759. 22 interactors.
IntActiQ4U2R8. 2 interactors.
MINTiMINT-1474237.
STRINGi9606.ENSP00000367102.

Chemistry databases

BindingDBiQ4U2R8.

Structurei

3D structure databases

ProteinModelPortaliQ4U2R8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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.
HOVERGENiHBG108433.
InParanoidiQ4U2R8.
KOiK08203.
OMAiGVVPQDQ.
OrthoDBiEOG091G07CO.
PhylomeDBiQ4U2R8.
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.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q4U2R8-1) [UniParc]FASTAAdd to basket
Also known as: OAT1-1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAFNDLLQQV GGVGRFQQIQ VTLVVLPLLL MASHNTLQNF TAAIPTHHCR
60 70 80 90 100
PPADANLSKN GGLEVWLPRD RQGQPESCLR FTSPQWGLPF LNGTEANGTG
110 120 130 140 150
ATEPCTDGWI YDNSTFPSTI VTEWDLVCSH RALRQLAQSL YMVGVLLGAM
160 170 180 190 200
VFGYLADRLG RRKVLILNYL QTAVSGTCAA FAPNFPIYCA FRLLSGMALA
210 220 230 240 250
GISLNCMTLN VEWMPIHTRA CVGTLIGYVY SLGQFLLAGV AYAVPHWRHL
260 270 280 290 300
QLLVSAPFFA FFIYSWFFIE SARWHSSSGR LDLTLRALQR VARINGKREE
310 320 330 340 350
GAKLSMEVLR ASLQKELTMG KGQASAMELL RCPTLRHLFL CLSMLWFATS
360 370 380 390 400
FAYYGLVMDL QGFGVSIYLI QVIFGAVDLP AKLVGFLVIN SLGRRPAQMA
410 420 430 440 450
ALLLAGICIL LNGVIPQDQS IVRTSLAVLG KGCLAASFNC IFLYTGELYP
460 470 480 490 500
TMIRQTGMGM GSTMARVGSI VSPLVSMTAE LYPSMPLFIY GAVPVAASAV
510 520 530 540 550
TVLLPETLGQ PLPDTVQDLE SRWAPTQKEA GIYPRKGKQT RQQQEHQKYM
560
VPLQASAQEK NGL
Length:563
Mass (Da):61,816
Last modified:July 19, 2005 - v1
Checksum:i74AD3EA2678032E4
GO
Isoform 2 (identifier: Q4U2R8-2) [UniParc]FASTAAdd to basket
Also known as: OAT1-2

The sequence of this isoform differs from the canonical sequence as follows:
     523-535: Missing.

Show »
Length:550
Mass (Da):60,318
Checksum:iBC5D6DBDD0072D92
GO
Isoform 3 (identifier: Q4U2R8-3) [UniParc]FASTAAdd to basket
Also known as: OAT1-3

The sequence of this isoform differs from the canonical sequence as follows:
     455-498: Missing.
     523-535: Missing.

Note: No experimental confirmation available.
Show »
Length:506
Mass (Da):55,858
Checksum:iD8EBAE8A113E6C5E
GO
Isoform 4 (identifier: Q4U2R8-4) [UniParc]FASTAAdd to basket
Also known as: OAT1-4

The sequence of this isoform differs from the canonical sequence as follows:
     455-498: Missing.

Note: No experimental confirmation available.
Show »
Length:519
Mass (Da):57,357
Checksum:iE1748C6F9E2002F2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14G → S in AAD10052 (PubMed:9950961).Curated1
Sequence conflicti563L → F in AAC70004 (PubMed:9762842).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0396827L → P1 Publication1
Natural variantiVAR_03968350R → H Lower Vmax; increase in substrate affinity and increase in the affinity for the nucleoside phosphonate analogs cidofovir, adefovir and tenofovir. 2 PublicationsCorresponds to variant dbSNP:rs11568626Ensembl.1
Natural variantiVAR_047878104P → L1 PublicationCorresponds to variant dbSNP:rs11568627Ensembl.1
Natural variantiVAR_039684293R → W Increase in substrate affinity. Corresponds to variant dbSNP:rs45607933Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032168455 – 498Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_032169523 – 535Missing in isoform 2 and isoform 3. 7 PublicationsAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF057039 mRNA. Translation: AAC70004.1.
AB009697 mRNA. Translation: BAA75072.1.
AB009698 mRNA. Translation: BAA75073.1.
AF104038 mRNA. Translation: AAD10052.1.
AF097490 mRNA. Translation: AAD19356.1.
AF124373 mRNA. Translation: AAD55356.1.
AJ249369 Genomic DNA. Translation: CAB77184.1.
AJ251529 mRNA. Translation: CAB94830.1.
AJ271205 mRNA. Translation: CAB97249.1.
EU567146 Genomic DNA. Translation: ACB21049.1.
AP001858 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74129.1.
CH471076 Genomic DNA. Translation: EAW74130.1.
CH471076 Genomic DNA. Translation: EAW74131.1.
CH471076 Genomic DNA. Translation: EAW74132.1.
BC033682 mRNA. Translation: AAH33682.1.
CCDSiCCDS31591.1. [Q4U2R8-1]
CCDS44631.1. [Q4U2R8-4]
CCDS44632.1. [Q4U2R8-3]
CCDS8041.1. [Q4U2R8-2]
RefSeqiNP_004781.2. NM_004790.4. [Q4U2R8-1]
NP_695008.1. NM_153276.2. [Q4U2R8-2]
NP_695009.1. NM_153277.2. [Q4U2R8-3]
NP_695010.1. NM_153278.2. [Q4U2R8-4]
UniGeneiHs.369252.

Genome annotation databases

EnsembliENST00000360421; ENSP00000353597; ENSG00000197901. [Q4U2R8-2]
ENST00000377871; ENSP00000367102; ENSG00000197901. [Q4U2R8-1]
ENST00000421062; ENSP00000404441; ENSG00000197901. [Q4U2R8-4]
ENST00000458333; ENSP00000396401; ENSG00000197901. [Q4U2R8-3]
GeneIDi9356.
KEGGihsa:9356.
UCSCiuc001nwj.4. human. [Q4U2R8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiS22A6_HUMAN
AccessioniPrimary (citable) accession number: Q4U2R8
Secondary accession number(s): A8MY93
, B2D0R6, O95187, O95742, Q7LDA0, Q8N192, Q9NQA6, Q9NQC2, Q9UBG6, Q9UEQ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: July 19, 2005
Last modified: October 25, 2017
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families