Q9NPD5 (SO1B3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier organic anion transporter family member 1B3

Alternative name(s):
Liver-specific organic anion transporter 2
Short name=LST-2
Organic anion transporter 8
Organic anion-transporting polypeptide 8
Short name=OATP-8
Solute carrier family 21 member 8

Gene names

Name:	SLCO1B3
Synonyms:	LST2, OATP1B3, OATP8,SLC21A8

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	702 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the Na+-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver. Ref.3
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein.
Tissue specificity	Highly expressed in liver, in particular at the basolateral membrane of hepatocytes near the central vein. Not detected in other tissues. Highly expressed in some cancer cell lines derived from colon, pancreas, liver and gall bladder.
Post-translational modification	N-glycosylated. Ref.1
Involvement in disease	Hyperbilirubinemia, Rotor type (HBLRR) [MIM:237450]: An autosomal recessive form of primary conjugated hyperbilirubinemia. Affected individuals develop mild jaundice not associated with hemolysis shortly after birth or in childhood. They have delayed plasma clearance of the unconjugated anionic dye bromsulphthalein and prominent urinary excretion of coproporphyrin I. Hepatic pigmentation is normal. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3
Sequence similarities	Belongs to the organo anion transporter (TC 2.A.60) family. [View classification] Contains 1 Kazal-like domain.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid and bile salt transport Traceable author statement. Source: Reactome bile acid metabolic process Traceable author statement. Source: Reactome sodium-independent organic anion transport Traceable author statement. Source: Reactome
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: HPA integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	organic anion transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 702	702	Solute carrier organic anion transporter family member 1B3		PRO_0000191053
Regions
	Topological domain	1 – 28	28	Cytoplasmic Potential
	Transmembrane	29 – 48	20	Helical; Name=1; Potential
	Topological domain	49 – 67	19	Extracellular Potential
	Transmembrane	68 – 88	21	Helical; Name=2; Potential
	Topological domain	89 – 94	6	Cytoplasmic Potential
	Transmembrane	95 – 119	25	Helical; Name=3; Potential
	Topological domain	120 – 168	49	Extracellular Potential
	Transmembrane	169 – 197	29	Helical; Name=4; Potential
	Topological domain	198 – 216	19	Cytoplasmic Potential
	Transmembrane	217 – 237	21	Helical; Name=5; Potential
	Topological domain	238 – 255	18	Extracellular Potential
	Transmembrane	256 – 280	25	Helical; Name=6; Potential
	Topological domain	281 – 331	51	Cytoplasmic Potential
	Transmembrane	332 – 353	22	Helical; Name=7; Potential
	Topological domain	354 – 373	20	Extracellular Potential
	Transmembrane	374 – 397	24	Helical; Name=8; Potential
	Topological domain	398 – 401	4	Cytoplasmic Potential
	Transmembrane	402 – 425	24	Helical; Name=9; Potential
	Topological domain	426 – 537	112	Extracellular Potential
	Transmembrane	538 – 560	23	Helical; Name=10; Potential
	Topological domain	561 – 569	9	Cytoplasmic Potential
	Transmembrane	570 – 595	26	Helical; Name=11; Potential
	Topological domain	596 – 629	34	Extracellular Potential
	Transmembrane	630 – 647	18	Helical; Name=12; Potential
	Topological domain	648 – 695	48	Cytoplasmic Potential
	Domain	453 – 508	56	Kazal-like
Amino acid modifications
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Glycosylation	145	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Glycosylation	445	1	N-linked (GlcNAc...) Potential
	Glycosylation	503	1	N-linked (GlcNAc...) Potential
	Glycosylation	516	1	N-linked (GlcNAc...) Potential
	Disulfide bond	459 ↔ 485		By similarity
	Disulfide bond	463 ↔ 474		By similarity
	Disulfide bond	465 ↔ 489		By similarity
Natural variations
	Natural variant	112	1	S → A. Corresponds to variant rs4149117 [ dbSNP | Ensembl ].		VAR_024645
	Natural variant	233	1	M → I. Corresponds to variant rs7311358 [ dbSNP | Ensembl ].		VAR_053672
	Natural variant	256	1	G → A. Corresponds to variant rs60140950 [ dbSNP | Ensembl ].		VAR_062150
	Natural variant	292	1	I → M in a colorectal cancer sample; somatic mutation. Ref.4		VAR_036410
	Natural variant	560	1	V → A. Corresponds to variant rs12299012 [ dbSNP | Ensembl ].		VAR_053673
	Natural variant	647	1	M → L in a colorectal cancer sample; somatic mutation. Ref.4		VAR_036411

Sequences

	Sequence		Length	Mass (Da)
	Q9NPD5 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6D2AE371D782C7FB	FASTA	702	77,403
	10 20 30 40 50 60 MDQHQHLNKT AESASSEKKK TRRCNGFKMF LAALSFSYIA KALGGIIMKI SITQIERRFD 70 80 90 100 110 120 ISSSLAGLID GSFEIGNLLV IVFVSYFGSK LHRPKLIGIG CLLMGTGSIL TSLPHFFMGY 130 140 150 160 170 180 YRYSKETHIN PSENSTSSLS TCLINQTLSF NGTSPEIVEK DCVKESGSHM WIYVFMGNML 190 200 210 220 230 240 RGIGETPIVP LGISYIDDFA KEGHSSLYLG SLNAIGMIGP VIGFALGSLF AKMYVDIGYV 250 260 270 280 290 300 DLSTIRITPK DSRWVGAWWL GFLVSGLFSI ISSIPFFFLP KNPNKPQKER KISLSLHVLK 310 320 330 340 350 360 TNDDRNQTAN LTNQGKNVTK NVTGFFQSLK SILTNPLYVI FLLLTLLQVS SFIGSFTYVF 370 380 390 400 410 420 KYMEQQYGQS ASHANFLLGI ITIPTVATGM FLGGFIIKKF KLSLVGIAKF SFLTSMISFL 430 440 450 460 470 480 FQLLYFPLIC ESKSVAGLTL TYDGNNSVAS HVDVPLSYCN SECNCDESQW EPVCGNNGIT 490 500 510 520 530 540 YLSPCLAGCK SSSGIKKHTV FYNCSCVEVT GLQNRNYSAH LGECPRDNTC TRKFFIYVAI 550 560 570 580 590 600 QVINSLFSAT GGTTFILLTV KIVQPELKAL AMGFQSMVIR TLGGILAPIY FGALIDKTCM 610 620 630 640 650 660 KWSTNSCGAQ GACRIYNSVF FGRVYLGLSI ALRFPALVLY IVFIFAMKKK FQGKDTKASD 670 680 690 700 NERKVMDEAN LEFLNNGEHF VPSAGTDSKT CNLDMQDNAA AN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide." Koenig J., Cui Y., Nies A.T., Keppler D. J. Biol. Chem. 275:23161-23168(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], GLYCOSYLATION. Tissue: Liver.
[2]	"LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers." Abe T., Unno M., Onogawa T., Tokui T., Kondo T.N., Nakagomi R., Adachi H., Fujiwara K., Okabe M., Suzuki T., Nunoki K., Sato E., Kakyo M., Nishio T., Sugita J., Asano N., Tanemoto M., Seki M. , Date F., Ono K., Kondo Y., Shiiba K., Suzuki M., Ohtani H., Shimosegawa T., Iinuma K., Nagura H., Ito S., Matsuno S. Gastroenterology 120:1689-1699(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver." van de Steeg E., Stranecky V., Hartmannova H., Noskova L., Hrebicek M., Wagenaar E., van Esch A., de Waart D.R., Oude Elferink R.P., Kenworthy K.E., Sticova E., al-Edreesi M., Knisely A.S., Kmoch S., Jirsa M., Schinkel A.H. J. Clin. Invest. 122:519-528(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN HBLRR.
[4]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-292 AND LEU-647.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ400763 , AJ400764, AJ400765, AJ400766, AJ400767, AJ400768, AJ400769, AJ400770, AJ400771, AJ400772, AJ400773, AJ400774, AJ400775, AJ400776 Genomic DNA. Translation: CAB97008.1. AJ251506 mRNA. Translation: CAB96997.1. AF187815 mRNA. Translation: AAG43445.1.
IPI	IPI00022873.
RefSeq	NP_062818.1. NM_019844.3.
UniGene	Hs.504966.
3D structure databases
ProteinModelPortal	Q9NPD5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000261196.
Protein family/group databases
TCDB	2.A.60.1.12. organo anion transporter (OAT) family.
PTM databases
PhosphoSite	Q9NPD5.
Polymorphism databases
DMDM	27734563.
Proteomic databases
PaxDb	Q9NPD5.
PRIDE	Q9NPD5.
Protocols and materials databases
DNASU	28234.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261196; ENSP00000261196; ENSG00000111700. ENST00000381545; ENSP00000370956; ENSG00000111700.
GeneID	28234.
KEGG	hsa:28234.
UCSC	uc001rek.3. human.
Organism-specific databases
CTD	28234.
GeneCards	GC12P020963.
HGNC	HGNC:10961. SLCO1B3.
HPA	HPA004943. HPA050892.
MIM	237450. phenotype. 605495. gene.
neXtProt	NX_Q9NPD5.
Orphanet	3111. Rotor syndrome.
PharmGKB	PA35844.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322696.
HOGENOM	HOG000231269.
HOVERGEN	HBG063896.
InParanoid	Q9NPD5.
KO	K05043.
OMA	FLNNGEH.
OrthoDB	EOG4V6ZGC.
PhylomeDB	Q9NPD5.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9NPD5.
Bgee	Q9NPD5.
CleanEx	HS_SLCO1B3.
Genevestigator	Q9NPD5.
GermOnline	ENSG00000111700. Homo sapiens.
Family and domain databases
InterPro	IPR002350. Kazal_dom. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004156. OA_transporter. [Graphical view]
PANTHER	PTHR11388. PTHR11388. 1 hit.
Pfam	PF07648. Kazal_2. 1 hit. PF03137. OATP. 1 hit. [Graphical view]
SMART	SM00280. KAZAL. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00805. oat. 1 hit.
PROSITE	PS51465. KAZAL_2. 1 hit. PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NPD5.
ChEMBL	CHEMBL1743121.
GenomeRNAi	28234.
NextBio	50556.
SOURCE	Search...

Entry information

Entry name

SO1B3_HUMAN

Accession

Primary (citable) accession number: Q9NPD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2003
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 106 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.