Q9NSA0 (S22AB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 22 member 11

Alternative name(s):
Organic anion transporter 4

Gene names

Name:	SLC22A11
Synonyms:	OAT4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	550 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds. Ref.1 Ref.7 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.7 Ref.9.
Tissue specificity	Detected in placenta and kidney. Ref.1
Post-translational modification	N-glycosylated. Contains several complex-type N-glycans. Ref.9
Sequence similarities	Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]
Sequence caution	The sequence BAC11483.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	urate metabolic process Inferred from mutant phenotype PubMed 19503597. Source: BHF-UCL
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 15037815. Source: UniProtKB external side of plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB integral to plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	inorganic anion exchanger activity Inferred from direct assay PubMed 15037815. Source: UniProtKB sodium-independent organic anion transmembrane transporter activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NSA0-1)

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.

Isoform 2 (identifier: Q9NSA0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     353-461: NFSLLISYYG...KAELFPTPVR → K

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 550	550	Solute carrier family 22 member 11		PRO_0000234435
Regions
	Topological domain	1 – 10	10	Cytoplasmic Potential
	Transmembrane	11 – 31	21	Helical; Potential
	Topological domain	32 – 142	111	Extracellular Potential
	Transmembrane	143 – 163	21	Helical; Potential
	Topological domain	164 – 174	11	Cytoplasmic Potential
	Transmembrane	175 – 195	21	Helical; Potential
	Topological domain	196 – 200	5	Extracellular Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Topological domain	222 – 231	10	Cytoplasmic Potential
	Transmembrane	232 – 252	21	Helical; Potential
	Topological domain	253 – 256	4	Extracellular Potential
	Transmembrane	257 – 277	21	Helical; Potential
	Topological domain	278 – 346	69	Cytoplasmic Potential
	Transmembrane	347 – 367	21	Helical; Potential
	Topological domain	368 – 378	11	Extracellular Potential
	Transmembrane	379 – 399	21	Helical; Potential
	Topological domain	400 – 402	3	Cytoplasmic Potential
	Transmembrane	403 – 423	21	Helical; Potential
	Topological domain	424 – 430	7	Extracellular Potential
	Transmembrane	431 – 451	21	Helical; Potential
	Topological domain	452 – 463	12	Cytoplasmic Potential
	Transmembrane	464 – 484	21	Helical; Potential
	Topological domain	485 – 490	6	Extracellular Potential
	Transmembrane	491 – 511	21	Helical; Potential
	Topological domain	512 – 550	39	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	39	1	N-linked (GlcNAc...) Potential
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	353 – 461	109	NFSLL…PTPVR → K in isoform 2.		VSP_018319
	Natural variant	155	1	V → G. Corresponds to variant rs12785832 [ dbSNP | Ensembl ].		VAR_053962
Experimental info
	Mutagenesis	39	1	N → Q: No visible effect on N-glycosylation. Loss of N-glycosylation and of cell surface location; when associated with Q-56; Q-63 and Q-99. Ref.9
	Mutagenesis	47	1	H → A: Reduced cell surface expression and estrone sulfate transport. Reduced cell surface expression and estrone sulfate transport; when associated with A-52; A-83; A-305 and A-469. Ref.7
	Mutagenesis	52	1	H → A: Slightly reduced estrone sulfate transport. Reduced cell surface expression and estrone sulfate transport; when associated with A-47; A-83; A-305 and A-469. Ref.7
	Mutagenesis	56	1	N → Q: No visible effect on N-glycosylation. Loss of N-glycosylation and of cell surface expression; when associated with Q-39; Q-63 and Q-99. Ref.9
	Mutagenesis	63	1	N → Q: No visible effect on N-glycosylation. Loss of N-glycosylation and of cell surface expression; when associated with Q-39; Q-56 and Q-99. Ref.9
	Mutagenesis	83	1	H → A: Reduced cell surface expression and estrone sulfate transport; when associated with A-47; A-52; A-305 and A-469. Ref.7
	Mutagenesis	99	1	N → Q: No visible effect on N-glycosylation. Loss of N-glycosylation and of cell surface expression; when associated with Q-39; Q-56 and Q-63. Ref.9
	Mutagenesis	241	1	G → L, S or V: Strongly reduced cell surface expression and estrone sulfate transport. Ref.8
	Mutagenesis	305	1	H → A: Reduced cell surface expression and estrone sulfate transport; when associated with A-47; A-52; A-83 and A-469. Ref.7
	Mutagenesis	400	1	G → L, S or V: Strongly reduced cell surface expression and estrone sulfate transport. Ref.8
	Mutagenesis	469	1	H → A: Slightly reduced estrone sulfate transport. Reduced cell surface expression and estrone sulfate transport; when associated with A-47; A-52; A-83 and A-305. Ref.7
	Sequence conflict	180	1	L → S in BAD96589. Ref.3
	Sequence conflict	376	1	L → R in BAC85252. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 233BE6C4A520E58A	FASTA	550	59,972
	10 20 30 40 50 60 MAFSKLLEQA GGVGLFQTLQ VLTFILPCLM IPSQMLLENF SAAIPGHRCW THMLDNGSAV 70 80 90 100 110 120 STNMTPKALL TISIPPGPNQ GPHQCRRFRQ PQWQLLDPNA TATSWSEADT EPCVDGWVYD 130 140 150 160 170 180 RSVFTSTIVA KWDLVCSSQG LKPLSQSIFM SGILVGSFIW GLLSYRFGRK PMLSWCCLQL 190 200 210 220 230 240 AVAGTSTIFA PTFVIYCGLR FVAAFGMAGI FLSSLTLMVE WTTTSRRAVT MTVVGCAFSA 250 260 270 280 290 300 GQAALGGLAF ALRDWRTLQL AASVPFFAIS LISWWLPESA RWLIIKGKPD QALQELRKVA 310 320 330 340 350 360 RINGHKEAKN LTIEVLMSSV KEEVASAKEP RSVLDLFCVP VLRWRSCAML VVNFSLLISY 370 380 390 400 410 420 YGLVFDLQSL GRDIFLLQAL FGAVDFLGRA TTALLLSFLG RRTIQAGSQA MAGLAILANM 430 440 450 460 470 480 LVPQDLQTLR VVFAVLGKGC FGISLTCLTI YKAELFPTPV RMTADGILHT VGRLGAMMGP 490 500 510 520 530 540 LILMSRQALP LLPPLLYGVI SIASSLVVLF FLPETQGLPL PDTIQDLESQ KSTAAQGNRQ 550 EAVTVESTSL
	Isoform 2 [UniParc]. Checksum: F9D42F38249733FB	FASTA	442	48,301
	10 20 30 40 50 60 MAFSKLLEQA GGVGLFQTLQ VLTFILPCLM IPSQMLLENF SAAIPGHRCW THMLDNGSAV 70 80 90 100 110 120 STNMTPKALL TISIPPGPNQ GPHQCRRFRQ PQWQLLDPNA TATSWSEADT EPCVDGWVYD 130 140 150 160 170 180 RSVFTSTIVA KWDLVCSSQG LKPLSQSIFM SGILVGSFIW GLLSYRFGRK PMLSWCCLQL 190 200 210 220 230 240 AVAGTSTIFA PTFVIYCGLR FVAAFGMAGI FLSSLTLMVE WTTTSRRAVT MTVVGCAFSA 250 260 270 280 290 300 GQAALGGLAF ALRDWRTLQL AASVPFFAIS LISWWLPESA RWLIIKGKPD QALQELRKVA 310 320 330 340 350 360 RINGHKEAKN LTIEVLMSSV KEEVASAKEP RSVLDLFCVP VLRWRSCAML VVKMTADGIL 370 380 390 400 410 420 HTVGRLGAMM GPLILMSRQA LPLLPPLLYG VISIASSLVV LFFLPETQGL PLPDTIQDLE 430 440 SQKSTAAQGN RQEAVTVEST SL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta." Cha S.H., Sekine T., Kusuhara H., Yu E., Kim J.Y., Kim D.K., Sugiyama Y., Kanai Y., Endou H. J. Biol. Chem. 275:4507-4512(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Kidney.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney and Placenta.
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Colon.
[7]	"Mutational analysis of histidine residues in human organic anion transporter 4 (hOAT4)." Zhou F., Pan Z., Ma J., You G. Biochem. J. 384:87-92(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-47; HIS-52; HIS-83; HIS-305 AND HIS-469, FUNCTION, SUBCELLULAR LOCATION.
[8]	"The role of glycine residues in the function of human organic anion transporter 4." Zhou F., Tanaka K., Pan Z., Ma J., You G. Mol. Pharmacol. 65:1141-1147(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-241 AND GLY-400.
[9]	"The role of N-linked glycosylation in protein folding, membrane targeting, and substrate binding of human organic anion transporter hOAT4." Zhou F., Xu W., Hong M., Pan Z., Sinko P.J., Ma J., You G. Mol. Pharmacol. 67:868-876(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-39; ASN-56; ASN-63 AND ASN-99, SUBCELLULAR LOCATION, GLYCOSYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB026116 mRNA. Translation: BAA95316.1. AK075224 mRNA. Translation: BAC11483.1. Different initiation. AK129930 mRNA. Translation: BAC85252.1. AK222869 mRNA. Translation: BAD96589.1. AK290791 mRNA. Translation: BAF83480.1. AC044790 Genomic DNA. Translation: AAK68155.1. CH471076 Genomic DNA. Translation: EAW74269.1. BC034384 mRNA. Translation: AAH34384.1.
IPI	IPI00020542. IPI00418660.
RefSeq	NP_060954.1. NM_018484.2.
UniGene	Hs.220844.
3D structure databases
ProteinModelPortal	Q9NSA0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000301891.
Protein family/group databases
TCDB	2.A.1.19.10. major facilitator superfamily (MFS).
Polymorphism databases
DMDM	74734337.
Proteomic databases
PaxDb	Q9NSA0.
PRIDE	Q9NSA0.
Protocols and materials databases
DNASU	55867.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000301891; ENSP00000301891; ENSG00000168065. ENST00000377585; ENSP00000366809; ENSG00000168065.
GeneID	55867.
KEGG	hsa:55867.
UCSC	uc001oai.3. human. uc009ypq.3. human.
Organism-specific databases
CTD	55867.
GeneCards	GC11P064324.
HGNC	HGNC:18120. SLC22A11.
HPA	HPA026076.
MIM	607097. gene.
neXtProt	NX_Q9NSA0.
PharmGKB	PA38295.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOGENOM	HOG000234569.
HOVERGEN	HBG108433.
InParanoid	Q9NSA0.
KO	K08207.
OMA	NPRHPME.
OrthoDB	EOG418BPG.
PhylomeDB	Q9NSA0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9NSA0.
Bgee	Q9NSA0.
CleanEx	HS_SLC22A11.
Genevestigator	Q9NSA0.
GermOnline	ENSG00000168065. Homo sapiens.
Family and domain databases
InterPro	IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR005828. Sub_transporter. [Graphical view]
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC22A11. human.
DrugBank	DB01032. Probenecid.
GenomeRNAi	55867.
NextBio	61178.
SOURCE	Search...

Entry information

Entry name

S22AB_HUMAN

Accession

Primary (citable) accession number: Q9NSA0
Secondary accession number(s): A8K426 , Q53GR2, Q6ZP72, Q8NBU4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	October 1, 2000
Last modified:	April 3, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.