SLC22A9 Membrane Protein Introduction

Introduction of SLC22A9

Solute carrier family 22 member 9 (SLC22A9), or organic anion transporter 7 (OAT7), is a protein that in humans is encoded by the SLC22A9 gene. SLC22A9 is a 553 amino acid protein and is restricted to the liver where it is located at the sinusoidal membrane. The expression of SLC22A9 is trans-activated by HNF-1α. The human SLC22A9 gene has been mapped to chromosomal region 11q13.1. Twenty-four variants of SLC22A9 have been genotyped, including three rare missense variants (rs377211288, rs61742518, rs146027075).

Basic Information of SLC22A9
Protein Name	Solute carrier family 22 member 9
Gene Name	SLC22A9
Aliases	Organic anion transporter 7, hOAT4, OAT7, UST3
Organism	Homo sapiens (Human)
UniProt ID	Q8IVM8
Transmembrane Times	12
Length (aa)	553
Sequence	MAFQDLLGHAGDLWRFQILQTVFLSIFAVATYLHFMLENFTAFIPGHRCWVHILDNDTVSDNDTGALSQDALLRISIPLDSNMRPEKCRRFVHPQWQLLHLNGTFPNTSDADMEPCVDGWVYDRISFSSTIVTEWDLVCDSQSLTSVAKFVFMAGMMVGGILGGHLSDRFGRRFVLRWCYLQVAIVGTCAALAPTFLIYCSLRFLSGIAAMSLITNTIMLIAEWATHRFQAMGITLGMCPSGIAFMTLAGLAFAIRDWHILQLVVSVPYFVIFLTSSWLLESARWLIINNKPEEGLKELRKAAHRSGMKNARDTLTLEILKSTMKKELEAAQKKKPSLCEMLHMPNICKRISLLSFTRFANFMAYFGLNLHVQHLGNNVFLLQTLFGAVILLANCVAPWALKYMNRRASQMLLMFLLAICLLAIIFVPQEMQTLREVLATLGLGASALANTLAFAHGNEVIPTIIRARAMGINATFANIAGALAPLMMILSVYSPPLPWIIYGVFPFISGFAFLLLPETRNKPLFDTIQDEKNERKDPREPKQEDPRVEVTQF

Function of SLC22A9 Membrane Protein

The solute carrier family 22 (SLC22) of human transporters consists of 23 members that cluster together based on sequence homology and substrate specificities into ‘organic cation transporters’ (OCTs), ‘organic cation/zwitterion cotransporters’ (OCTNs) and ‘organic anion transporters’ (OATs). Human organic anion transporter 7 (OAT7, SLC22A9) is a hepatic transport protein poorly characterized so far. Since its initial discovery in 2007 as a novel liver-specific transporter localized to the sinusoidal hepatocyte membrane, further functional characterization and studies on the inter-individual variability of its hepatic expression have not been undertaken. To date, no clinically relevant SLC22A9 substrates have been identified. Moreover, several well-established substrates and inhibitors for other OATs (for example, probenecid, Para-aminohippurate (PAH), nonsteroidal anti-inflammatory drugs, diuretics) failed to inhibit SLC22A9. It has been reported that activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodeling of the temporomandibular joint.

Fig.1 Selected transporters for endogenous compounds and xenobiotics, expressed on the sinusoidal and canalicular membranes of human hepatocytes. (Niemi, 2011)

Application of SLC22A9 Membrane Protein in Literature

Vildhede A., et al. Quantification of Hepatic Organic Anion Transport Proteins OAT2 and OAT7 in Human Liver Tissue and Primary Hepatocytes. Mol Pharm. 2018, 15(8):3227-3235. PubMed ID: 29906129

This article found that OAT7 showed less interindividual variability (4-fold) in the livers, but high variability for the hepatocyte lots (27-fold).
Emami Riedmaier A., et al. Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors. Pharmacogenomics J. 2016, 16(4): 341-351. PubMed ID: 26239079

This article revealed that hepatic nuclear factor 4-alpha (HNF4α) emerged as a major transcriptional regulator of SLC22A9.
Jouan E., et al. Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells. Pharmaceutics. 2016, 9(1): E3. PubMed ID: 28036031

The authors in this article characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays and they demonstrated that OAT7, MRP4 and MRP5 were up-regulated in HuH-7 cell.
Klein K., et al. The human organic anion transporter genes OAT5 and OAT7 are transactivated by hepatocyte nuclear factor-1α (HNF-1α). Mol Pharmacol. 2010, 78(6): 1079-1087. PubMed ID: 20829431

This article revealed that the short interfering RNAs targeting HNF-1α could reduce endogenous expression of OAT5 and OAT7, but not OAT2.
Shin H.J., et al. Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate. Hepatology. 2007, 45(4): 1046-1055. PubMed ID: 17393504

This article showed that OAT7 was the first liver-specific transporter among members of the organic anion transporters of SLC22 family.

SLC22A9 Preparation Options

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Reference

Niemi M, et al. (2011). Organic Anion Transporting Polypeptide 1B1: a Genetically Polymorphic Transporter of Major Importance for Hepatic Drug Uptake. Pharmacological Reviews. 63(1): 157-181.

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