Summary: Organic Anion Transporter Polypeptide (OATP) family
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This is the Wikipedia entry entitled "Organic anion-transporting polypeptide". More...
Organic anion-transporting polypeptide Edit Wikipedia article
| Organic Anion Transporter Polypeptide (OATP) family | |||||||||
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| Identifiers | |||||||||
| Symbol | OATP | ||||||||
| Pfam | PF03137 | ||||||||
| InterPro | IPR004156 | ||||||||
| TCDB | 2.A.60 | ||||||||
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An organic anion-transporting polypeptide (OATP) is a membrane transport protein or 'transporter' that mediates the transport of mainly organic anions across the cell membrane. Therefore OATPs are present in the lipid bilayer of the cell membrane, acting as the cell's gatekeepers. OATPs belong to the Solute Carrier Family (SLC), more specifically the Solute Carrier Organic Anion (SLCO) gene subfamily [1]
Contents |
[edit] Function
Organic anion transporting polypeptides carry bile acids as well as bilirubin and numerous hormones such as thyroid and steroid hormones across the basolateral membrane (facing sinusoids) in hepatocytes, for excretion in bile.[2] As well as expression in the liver, OATPs are expressed in many other tissues on basolateral and apical membranes, transporting anions, as well as neutral and even cationic compounds. They also transport an extremely diverse range of drug compounds, ranging from anti-cancer, antibiotic, lipid lowering to anti-diabetic drugs, as well as toxins and poisons.
They also transport the dye bromsulphthalein, availing it as a liver-testing substance.[2]
[edit] Proteins
The table below shows the 11 known human OATPs. Note: Human OATPs are designated with capital letters, animal Oatps are designated with lower class letters. The 'SLCO' stands for their gene name; 'solute carrier organic anion.' Previous nomenclature using letters and numbers (e.g. OATP-A, OATP-8 is no longer correct. The most well characterised human OATPs are OATP1A2, OATP1B1, OATP1B3 and OATP2B1. Very little is known about the function and characteristics of OATP5A1 and OATP6A1.
| Abbreviation | Protein Name | Location |
|---|---|---|
| SLCO1A2 | Solute carrier organic anion transporter family member 1A2 | Ubiquitous |
| SLCO1B1 | Solute carrier organic anion transporter family member 1B1 | Liver |
| SLCO1B3 | Solute carrier organic anion transporter family member 1B3 | Liver |
| SLCO1C1 | Solute carrier organic anion transporter family member 1C1 | Brain, testis |
| SLCO2A1 | Solute carrier organic anion transporter family member 2A1 | Ubiquitous |
| SLCO2B1 | Solute carrier organic anion transporter family member 2B1 | Ubiquitous |
| SLCO3A1 | Solute carrier organic anion transporter family member 3A1 | Testis, brain, heart, lung, spleen |
| SLCO4A1 | Solute carrier organic anion transporter family member 4A1 | Heart, placenta, lung, liver |
| SLCO4C1 | Solute carrier organic anion transporter family member 4C1 | Kidney |
| SLCO5A1 | Solute carrier organic anion transporter family member 5A1 | Breast, fetal brain, prostate |
| SLCO6A1 | Solute carrier organic anion transporter family member 6A1 | Testes, spleen, brain, placenta |
[edit] Pharmacology
The OATPs play a fundamental role in the transport of drugs across the cell membrane, particularly in the liver and kidney. In the liver, OATPs are expressed on the basolateral membrane of hepatocytes, transporting compounds into the hepatocyte for biotransformation. A number of drug-drug interactions have been associated with the OATPs, affecting the pharmacokinetics and pharmacodynamics of drugs. This is most commonly where one drug inhibits the transport of another drug into the hepatocyte, so that it is retained in the body. The OATPs most associated with these interactions are OATP1B1, OATP1B3 and OATP2B1, which are all present on the hepatocyte basolateral membrane. The most clinically relevant interactions have been associated with the lipid lowering drugs statins, which led to the removal of cerivastatin from the market in 2002. Single nucleotide polymorphisms (SNPs) are also associated with the OATPs; particularly OATP1B1, causing
Probenecid inhibits organic anion transporting polypeptides.[3]
It is likely that along with the Organic Anion Transporters, Organic Cation transporters and the ATP-binding cassette transporters, the OATPs play a central role in the absorption, distribution, metabolism and exretion (ADME) of drug compounds.
[edit] Evolution
Oatps are present in many animals, including zebrafish, dog, cow, rat, mouse, monkey and horse. Oatps are not present in bacteria, indicating their evolution from the animal kingdom. However homologs do not correlate well with the human OATPs and therefore it is likely that isoforms arose by gene duplication. An Oatp has however been found in the little skate (Raja erinacea), suggesting that their evolution was early in the formation of the animal kingdom.
[edit] References
- ^ Hagenbuch B, Meier PJ (February 2004). "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties". Pflugers Arch. 447 (5): 653â65. doi:10.1007/s00424-003-1168-y. PMID 14579113.
- ^ a b Pages 980-990 in:Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3.
- ^ Price KL, Sautin YY, Long DA, Zhang L, Miyazaki H, Mu W, Endou H, Johnson RJ (July 2006). "Human vascular smooth muscle cells express a urate transporter". J. Am. Soc. Nephrol. 17 (7): 1791â5. doi:10.1681/ASN.2006030264. PMID 16775029.
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Organic Anion Transporter Polypeptide (OATP) family Provide feedback
This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules). Thus, Tamai et al. [1] initiated the current scheme of using digits for rat OATPs and letters for human ones. Prostaglandin transporter (PGT) proteins (e.g. Q92959) are also considered to be OATP family members. In addition, the methotrexate transporter OATK (P70502) is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. Note: Members of this family are described (in the Swiss-Prot database) as belonging to the SLC21 family of transporters.
Literature references
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Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A; , Biochem Biophys Res Commun 2000;273:251-260.: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. PUBMED:10873595 EPMC:10873595
External database links
| PANDIT: | PF03137 |
| Pseudofam: | PF03137 |
| SYSTERS: | OATP |
| Transporter classification: | 2.A.60 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR004156
This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules) so a scheme of using digits for rat OATPs and letters for human ones was introduced [PUBMED:10873595]. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. Note: Members of this family are described (in the UniProtKB/Swiss-Prot database) as belonging to the SLC21 family of transporters.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Cellular component | membrane (GO:0016020) |
| Molecular function | transporter activity (GO:0005215) |
| Biological process | transport (GO:0006810) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan MFS (CL0015), which contains the following 25 members:
Acatn ATG22 BT1 CLN3 DUF1228 DUF791 Folate_carrier FPN1 FTR1 LacY_symp MFS_1 MFS_1_like MFS_2 MFS_3 MFS_Mycoplasma Nodulin-like Nuc_H_symport Nucleoside_tran OATP PTR2 PUCC Sugar_tr TLC TRI12 UNC-93Alignments
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| Seed (16) |
Full (1462) |
Representative proteomes | NCBI (1674) |
Meta (81) |
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| RP15 (328) |
RP35 (378) |
RP55 (620) |
RP75 (852) |
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| PP/heatmap | 1 | |||||||
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| Seed (16) |
Full (1462) |
Representative proteomes | NCBI (1674) |
Meta (81) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (328) |
RP35 (378) |
RP55 (620) |
RP75 (852) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_626 (release 6.5) |
| Previous IDs: | OATP_C; |
| Type: | Family |
| Author: | Mifsud W, Bateman A |
| Number in seed: | 16 |
| Number in full: | 1462 |
| Average length of the domain: | 439.80 aa |
| Average identity of full alignment: | 25 % |
| Average coverage of the sequence by the domain: | 82.67 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 539 | ||||||||||||
| Family (HMM) version: | 15 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the OATP domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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Archea
Eukaryota
Bacteria
Other sequences
Viruses
Unclassified
Viroids
Unclassified sequence