Disease relevance of SLC22A2

• It has previously been demonstrated that in cultured and in situ tumour cells of classical Hodgkin lymphoma (cHL), the immunoglobulin (Ig) promoter is inactive and its transcription factors Oct2 and/or BOB.1/OBF.1 are down-regulated [1].
• Lower Prevalence of the OCT2 Ser270 Allele in Patients with Essential Hypertension* [2].
• A hypothetical three-dimensional structure of OCT2 based on a homology model that used the Escherichia coli glycerol 3-phosphate transporter as a template has been described (Zhang, X., Shirahatti, N. V., Mahadevan, D., and Wright, S. H. (2005) J. Biol. Chem. 280, 34813-34822) [3].

High impact information on SLC22A2

• Reintroduction of PU.1 and Oct2 in cultured HRS cells restored the activity of cotransduced immunoglobulin enhancer constructs [4].
• We recently demonstrated that defective immunoglobulin promoter transcription correlates with the down-regulation of the B-cell transcription factors Oct2 and BOB.1/OBF [4].
• These data demonstrate that cysteine 474 of OCT2 is exposed to the aqueous milieu of the cleft and contributes to forming a pathway for organic cation transport [3].
• The transport of TEA by hOCT2-A-transfected cells was saturable with the apparent Km value of 63 microM. hOCT2-A stimulated the uptake of TEA, 1-methyl-4-phenylpyridinium, and cimetidine as well as did hOCT2 [5].
• The uptake of TEA mediated by hOCT2-A but not by hOCT2 was inhibited significantly by organic cations such as procainamide, N-acetylprocainamide, and levofloxacin, indicating that hOCT2-A differs from hOCT2 in its affinity for several compounds [5].

Biological context of SLC22A2

• The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26 [6].
• Since EMT and OCT2 may play important roles in catecholamine homeostasis and, as such, are candidate genes in human disease, the present results provide a basis for the analysis of genetic variation and the regulation of transcription [7].
• In contrast, the OCT2 promoter is not associated with a CpG island, contains a putative TATA box, and potential binding sites for specific transcription factors, such as HFH-8 and IK2 [7].
• From direct DNA sequencing, 7 of 13 coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs), including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs [8].
• The functional changes of hOCT2 variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were compared among different ethnic populations [8].

Anatomical context of SLC22A2

• After expression in Xenopus laevis oocytes, hOCT1 and hOCT2 mediate tracer influx of N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), and 1-methyl-4-phenylpyridinium (MPP) [9].
• We calculate from the available literature and compare consensus transport efficiency (clearance) data for human and rat EMT, OCT1 and OCT2, expressed in transfected cell lines [10].
• In rat brain, OCT2 and OCT3 mRNAs are expressed predominantly in regions located at the brain-cerebrospinal fluid border, with OCT3 mRNA expression extending to regions that belong to monoaminergic pathways such as raphe nuclei, striatum and thalamus [11].
• RT-PCR revealed expression of OCT3 mRNA, but not OCT1 or OCT2 mRNA, in the medial hypothalamus [12].
• PURPOSE: To assess whether baseline retinal nerve fiber layer (RNFL) measurements obtained with optical coherence tomography (OCT2; Carl Zeiss Meditec, Dublin, California, USA) are predictive of the development of glaucomatous change [13].

Associations of SLC22A2 with chemical compounds

• However, oxaliplatin showed almost no influence on the TEA uptakes in the HEK293 cells expressing hOCT1, hOCT2, and hOCT3 [14].
• The contribution of each hOCT was evaluated based on measurements of the intracellular concentrations of haloperidol metabolites in Madin Darby canine kidney (MDCK) cells transfected with hOCT1, hOCT2, or hOCT3 [15].
• Renal Transport of Adefovir, Cidofovir, and Tenofovir by SLC22A Family Members (hOAT1, hOAT3, and hOCT2) [16].
• The TEs of OCT1 and OCT2 for dopamine, noradrenaline, adrenaline and 5-HT in general are rather low, in the range relative to MPP+ of 5%-15% [10].
• This selection may be due to a necessary role of OCT2 in the renal elimination of endogenous amines or xenobiotics, including environmental toxins, neurotoxic amines and therapeutic drugs [17].

Physical interactions of SLC22A2

• The half-maximal inhibitory concentrations of famotidine for [3H]estrone sulfate transport by hOAT3 and [14C]tetraethylammonium transport by hOCT2 (300 microM and 1.8 mM, respectively) were higher than those of cimetidine (53 and 67 microM, respectively) [18].

Other interactions of SLC22A2

• The EMT gene is 77 kb, and the OCT2 gene is 45 kb in size [7].
• SLC22A1 and SLC22A2 localized to the same locus, demonstrating the conservation of the close physical linkage of these three organic cation transporter genes in mouse and human [19].
• The Ki values of several compounds in interacting with hOCT1 differed substantially from the corresponding values for the rat organic cation transporter, rOCT1, and the human kidney-specific organic cation transporter, hOCT2, determined in previous studies [20].

Analytical, diagnostic and therapeutic context of SLC22A2

• This study investigated the association of the OCT2 Ala270Ser polymorphism with essential hypertension and its impact on blood pressure status in 607 Caucasian patients who underwent left heart catheterization [2].
• Inhibition of Ca2+/CaM complex resulted in a significant decrease of Vmax (160-99 photons/s) that can be explained in part by a reduction of the membrane-associated hOCT2 (-22 +/- 6%, n = 9) as determined using FACScan flow cytometry [21].

References