SLCO1B3

From Wikipedia, the free encyclopedia

Solute carrier organic anion transporter family, member 1B3

Identifiers

SLCO1B3; HBLRR; LST-2; LST-3TM13; LST3; OATP-8; OATP1B3; OATP8; SLC21A8

External IDs

OMIM: 605495 MGI: 1351899 HomoloGene: 75119 ChEMBL: 1743121 GeneCards: SLCO1B3 Gene

Gene Ontology
Molecular function	• organic anion transmembrane transporter activity
Cellular component	• cytoplasm • plasma membrane • integral to plasma membrane • basolateral plasma membrane
Biological process	• bile acid metabolic process • organic anion transport • bile acid and bile salt transport • sodium-independent organic anion transport • small molecule metabolic process • transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
20.96 – 21.24 Mb

Chr 6:
141.63 – 141.69 Mb

PubMed search

Solute carrier organic anion transporter family member 1B3 (SLCO1B3) also known as organic anion-transporting polypeptide 1B3 (OATP1B3) is a protein that in humans is encoded by the SLCO1B3 gene.^[1]

OATP1B3 is a 12-transmembrane domain influx transporter. Normally expressed in the liver, the transporter functions to uptake large, non-polar drugs and hormones from the portal vein.

Clinical significance

OATP1B3 has also been identified as a transporter aberrantly expressed in prostate cancer and implicated in prostate cancer progression.^[2] Increasing mRNA expression of OATP1B3 was also correlated to prostate cancer Gleason score.^[3]

In addition, lower expression of OATP1B3 mRNA was also detected in testicular cancer.^[3]

Substrates

Small molecules that are transported by SLCO1B3 include:^[4]

Amanitin
Atrasentan
Bilirubin
Bosentan
BQ-123
Bromsulphthalein (BSP)
CDCA-NBD
Cholate (CA)
Cholecystokinin octapeptide (CCK-8)
Dehydroepiandroserone-3-sulfate (DHEAS)
Deltorphin II
Demethylphalloin
Digoxin
Docetaxel
[D-penicillamine2,5]enkephalin (DPDPE)
Enalapril
Estradiol-17β-glucuronide 5–25
Estrone-3-sulfate
Fexofenadine
Fluvastatin
Fluo-3
Glutathione (GSH)
Glycocholate (GCA)
Glycoursodeoxycholate (GUDCA)
Irinotecan
Leukotriene C4 (LTC4)
Methotrexate
Microcystin
Monoglyucuronosyl
Olmesartan
Ouabain
Paclitaxel
Phalloidin
Pitavastatin
Rifampicin
Ro 48-5033 (Bosentan metabolite)
Rosuvastatin
SN-38
Taurocholate (TCA)
Taurochenodeoxycholate (TCDCA)
Taurodeoxycholate (TDCA)
Tauroursodeoxycholate (TUDCA)
Telmisartan
Thyroxine (T4)
TR-14035
Triiodothyronine (T3)
Valsartan

References

↑ "Entrez Gene: SLCO1B3 solute carrier organic anion transporter family, member 1B3".
↑ Hamada A, Sissung T, Price DK, Danesi R, Chau CH, Sharifi N, Venzon D, Maeda K, Nagao K, Sparreboom A, Mitsuya H, Dahut WL, Figg WD (June 2008). "Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-independent prostatic cancer". Clin. Cancer Res. 14 (11): 3312–8. doi:10.1158/1078-0432.CCR-07-4118. PMC 2701141. PMID 18519758.
↑ 3.0 3.1 Heather Pressler, Tristan M. Sissung, David Venzon, Douglas K. Price, William D. Figg (May 2011). "Expression of OATP Family Members in Hormone-Related Cancers: Potential Markers of Progression". Clin. Cancer Res. 6 (5): e20372. doi:10.1371/journal.pone.0020372. PMC 3098289. PMID 21625523.
↑ Hagenbuch B, Gui C (July 2008). "Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family". Xenobiotica 38 (7–8): 778–801. doi:10.1080/00498250801986951. PMID 18668430.

König J, Cui Y, Nies AT, Keppler D (2000). "Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide". J. Biol. Chem. 275 (30): 23161–8. doi:10.1074/jbc.M001448200. PMID 10779507.
Abe T, Unno M, Onogawa T, et al. (2001). "LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers". Gastroenterology 120 (7): 1689–99. doi:10.1053/gast.2001.24804. PMID 11375950.
Ismair MG, Stieger B, Cattori V, et al. (2001). "Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver". Gastroenterology 121 (5): 1185–90. doi:10.1053/gast.2001.28704. PMID 11677211.
Jung D, Podvinec M, Meyer UA, et al. (2002). "Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor". Gastroenterology 122 (7): 1954–66. doi:10.1053/gast.2002.33583. PMID 12055601.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Cui Y, König J, Nies AT, et al. (2003). "Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma". Lab. Invest. 83 (4): 527–38. PMID 12695556.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Vavricka SR, Jung D, Fried M, et al. (2004). "The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma". J. Hepatol. 40 (2): 212–8. doi:10.1016/j.jhep.2003.10.008. PMID 14739090.
Hirano M, Maeda K, Shitara Y, Sugiyama Y (2004). "Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans". J. Pharmacol. Exp. Ther. 311 (1): 139–46. doi:10.1124/jpet.104.068056. PMID 15159445.
Letschert K, Keppler D, König J (2005). "Mutations in the SLCO1B3 gene affecting the substrate specificity of the hepatocellular uptake transporter OATP1B3 (OATP8)". Pharmacogenetics 14 (7): 441–52. doi:10.1097/01.fpc.0000114744.08559.92. PMID 15226676.
Yamaguchi H, Okada M, Akitaya S, et al. (2006). "Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3". J. Lipid Res. 47 (6): 1196–202. doi:10.1194/jlr.M500532-JLR200. PMID 16534140.
Ohtsuka H, Abe T, Onogawa T, et al. (2006). "Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene". J. Gastroenterol. 41 (4): 369–77. doi:10.1007/s00535-006-1784-3. PMID 16741617.
Briz O, Romero MR, Martinez-Becerra P, et al. (2006). "OATP8/1B3-mediated cotransport of bile acids and glutathione: an export pathway for organic anions from hepatocytes?". J. Biol. Chem. 281 (41): 30326–35. doi:10.1074/jbc.M602048200. PMID 16877380.
Mahagita C, Grassl SM, Piyachaturawat P, Ballatori N (2007). "Human organic anion transporter 1B1 and 1B3 function as bidirectional carriers and do not mediate GSH-bile acid cotransport". Am. J. Physiol. Gastrointest. Liver Physiol. 293 (1): G271–8. doi:10.1152/ajpgi.00075.2007. PMID 17412826.
Treiber A, Schneiter R, Häusler S, Stieger B (2007). "Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil". Drug Metab. Dispos. 35 (8): 1400–7. doi:10.1124/dmd.106.013615. PMID 17496208.
Muto M, Onogawa T, Suzuki T, et al. (2007). "Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma". Cancer Sci. 98 (10): 1570–6. doi:10.1111/j.1349-7006.2007.00570.x. PMID 17760952.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1) high affinity glutamate and neutral amino-acid transporter (SLC1A1, 2, 3, 4, 5, 6, 7)

(2) facilitative GLUT transporter (SLC2A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)

(3) heavy subunits of heterodimeric amino-acid transporters (SLC3A1, 2)

(4) bicarbonate transporter (SLC4A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

(5) sodium glucose cotransporter (SLC5A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

(6) sodium- and chloride- dependent sodium:neurotransmitter symporters (SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC6A10, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A20)

(7) cationic amino-acid transporter/glycoprotein-associated (SLC7A1, SLC7A2, SLC7A3, SLC7A4) glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC7A14)

(8) Na+/Ca2+ exchanger (SLC8A1, SLC8A2, SLC8A3)

(9) Na+/H+ exchanger (SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11)

(10) sodium bile salt cotransport (SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC10A6, SLC10A7); 10A1 · 10A2 · 10A3 · 10A7

SLC11–20

(11) proton coupled metal ion transporter (SLC11A1, SLC11A2) 11A3

(12) electroneutral cation-Cl cotransporter (SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9)

(13) human Na+-sulfate/carboxylate cotransporter (SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5)

(14) urea transporter (SLC14A1, SLC14A2)

(15) proton oligopeptide cotransporter (SLC15A1, SLC15A2, SLC15A3, SLC15A4)

(16) monocarboxylate transporter (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14)

(17) vesicular glutamate transporter (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9)

(18) vesicular amine transporter (SLC18A1, SLC18A2, SLC18A3)

(19) folate/thiamine transporter (SLC19A1, SLC19A2, SLC19A3)

(20) type III Na+-phosphate cotransporter (SLC20A1, SLC20A2)

SLC21–30

(21) organic anion transporting (SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B4, SLCO1C1) (SLCO2A1, SLCO2B1) (SLCO3A1) (SLCO4A1, SLCO4C1) (SLCO5A1) (SLCO6A1)

(22) organic cation/anion/zwitterion transporter (SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A10, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A19, SLC22A20)

(23) Na+-dependent ascorbic acid transporter (SLC23A1, SLC23A2, SLC23A3, SLC23A4)

(24) Na+/(Ca2+-K+) exchanger (SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6)

(25) mitochondrial carrier (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, SLC25A9, SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46)

(26) multifunctional anion exchanger (SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11)

(27) fatty acid transport proteins (SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, SLC27A6)

(28) Na+-coupled nucleoside transport (SLC28A1, SLC28A2, SLC28A3

(29) facilitative nucleoside transporter (SLC29A1, SLC29A2, SLC29A3, SLC29A4)

(30) zinc efflux (SLC30A1, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A8, SLC30A9, SLC30A10)

SLC31–40

(31) copper transporter (SLC31A1)

(32) vesicular inhibitory amino-acid transporter (SLC32A1)

(33) Acetyl-CoA transporter (SLC33A1)

(34) type II Na+-phosphate cotransporter (SLC34A1, SLC34A2, SLC34A3)

(35) nucleoside-sugar transporter (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5) (SLC35B1, SLC35B2, SLC35B3, SLC35B4) (SLC35C1, SLC35C2) (SLC35D1, SLC35D2, SLC35D3) (SLC35E1, SLC35E2, SLC35E3, SLC35E4)

(36) proton-coupled amino-acid transporter (SLC36A1, SLC36A2, SLC36A3, SLC36A4)36A2 ·

(37) sugar-phosphate/phosphate exchanger (SLC37A1, SLC37A2, SLC37A3, SLC37A4)

(38) System A & N, sodium-coupled neutral amino-acid transporter (SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6, SLC38A10)

(39) metal ion transporter (SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14)

(40) basolateral iron transporter (SLC40A1)

SLC41–48

(41) MgtE-like magnesium transporter (SLC41A1, SLC41A2, SLC41A3)

(42) Ammonia transporter (RhAG, RhBG, RhCG)

(43) Na+-independent, system-L like amino-acid transporter (SLC43A1, SLC43A2, SLC43A3)

(44) Choline-like transporter (SLC44A1, SLC44A2, SLC44A3, SLC44A4, SLC44A5)

(45) Putative sugar transporter (SLC45A1, SLC45A2, SLC54A3, SLC45A4)

(46) Folate transporter (SLC46A1, SLC46A2)

(47) multidrug and toxin extrusion (SLC47A1, SLC47A2)

(48) Heme transporter

SLCO1–4

O1A2 · O1B1 · O1B3 · O2B1 · O431 · O4A1

Ion pumps

Symporter, Cotransporter	Na+/K+/2Cl- - Na/Pi3 - Na+/Cl- - Na/glucose - Na+/I- - Cl-/K+ (4, 5)

Antiporter (exchanger)	Na+/H+ - Na+/Ca2+ (Na+/(Ca2+-K+)) - Cl-/HCO3- (Band 3) - Cl-formate exchanger - Cl-oxalate exchanger

see also solute carrier disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), other

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SLCO1B3

Clinical significance

Substrates

See also

References

Further reading