Disease relevance of SLC14A1

• In this study we demonstrate that the gene encoding the small leucine-rich proteoglycan biglycan is expressed in human myometrial tissue and in the human leiomyosarcoma cell line SK-UT-1 [1].
• Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. III. A single VKII gene and one of several JK genes are joined by an invariant arginine to form the most common L chain V region [2].
• Dehydration induced by water deprivation for 2 days caused a tissue-specific decrease in UT-B1 abundance in the urinary bladder and the ureter [3].
• CONCLUSION: UTE pulse sequences provide anatomical detail not apparent with conventional sequences, demonstrate differences in T2* and show patterns of both increased and decreased enhancement in tendinopathy [4].
• In addition, the JK minigene was used in C108G VK, JK2, is apparently over-represented in anti-HIV-1 mAbs/Fabs; this minigene was used in 61% of the anti-gp120 human Fabs recently described and in three other anti-CD4-binding site human mAbs derived by EBV transformation [5].

High impact information on SLC14A1

• To elucidate the physiological role of the latter urea transporter, we have isolated the rat homologue (UT3) of HUT11 and studied its distribution of expression and functional characteristics [6].
• Rat UT2 has 88% amino acid sequence identity to rabbit UT2 and 64% identity to the recently cloned human erythrocyte urea transporter, HUT11 (Olives, B., P. Neav, P. Bailly, M.A. Hediger, G. Rousselet, J.P. Cartron, and P. Ripoch J. Biol. Chem. 1994. 269:31649-31652) [7].
• Clonal rearrangement of the immunoglobulin JH and JK genes was present, confirming the presence of a clonal B-cell proliferation [8].
• Southern blot and exon mapping analyses revealed an internal deletion within the Kidd (JK) locus encompassing exons 4 and 5 [9].
• Partial deletion in the JK locus causing a Jk(null) phenotype [9].

Biological context of SLC14A1

• HUT11 carries 2 putative glycosylation sites and 10 cysteines, of which only 7 are conserved at an equivalent position in UT2 [10].
• This also assigns the Kidd blood group locus (JK) to chromosome 18 [11].
• STUDY DESIGN AND METHODS: Blood samples from individuals of Swedish, Polynesian, and Finnish origin were collected and characterized by routine JK blood group serology and JK genotyping [12].
• Genomic DNA covering the exons and intervening introns of the JK gene coding region was amplified by polymerase chain reaction, and fragments were directly sequenced [12].
• Potential use of the presented method can be predicted in clinical transfusion medicine including prenatal determination of the JK genotype in a fetus at risk for HDN caused by JK antibodies [13].

Anatomical context of SLC14A1

• Antigenic and functional properties of the human red blood cell urea transporter hUT-B1 [14].
• Moreover, immunoadsorption studies, using inside-out and right-side-out red cell membrane vesicles as competing antigen, demonstrated that the C- and N-terminal ends of hUT-B1 are oriented intracellularly [14].
• No unidirectional movements of charged molecules, glycerol, or water were associated with HUT11 expression in oocytes [10].
• We now report the cloning and characterization of a complementary DNA (HUT11) encoding an urea transporter isolated from a human bone marrow library [10].
• The Kidd (JK) blood group locus encodes a urea transporter that is expressed on human red cells and on endothelial cells of the vasa recta in the kidney [15].

Associations of SLC14A1 with chemical compounds

• Altogether, these antigenic, topologic, and functional properties might have implications into the physiology of hUT-B1 and other members of the urea transporter family [14].
• Expression studies in Xenopus oocytes demonstrated that HUT11 mediates a facilitated urea transport that was inhibited, as described in mammalian erythrocytes, by very low concentrations of phloretin, p-chloromercuribenzene sulfonate, and urea analogues [10].
• A rabbit antibody raised against the predicted NH2-terminal amino-acids of the HUT11 protein reacted on immunoblots with a 46-60-kDa component present in all human erythrocytes except those from Jk(a-b-) individuals [16].
• Here, we report the identification in human erythroblasts of a novel cDNA, designated HUT11A, which encodes a protein identical to the previously reported erythroid HUT11 urea transporter, except for a Lys(44) --> Glu substitution and a Val-Gly dipeptide deletion after proline 227, which leads to a polypeptide of 389 residues versus 391 in HUT11 [15].
• The transepithelial flux of (14)C urea was examined in Caco-2 cells growing on porous membrane support and was significantly inhibited by phloretin, 1,3-dimethylurea, and thiourea, suggesting that the transfer of urea across the Caco-2 monolayer could be mediated, at least in part, by the UT-B urea transporter [17].
• When we co-injected UT-A1 with snapin cRNA in Xenopus oocytes, urea influx was significantly increased [18].

Physical interactions of SLC14A1

• Jk(a-b-) cells have neither Kidd protein nor HUT11 urea transporter and they are characterized by a selective defect of urea transport whereas water transport and aquaporin-1 associated Colton antigens are normally expressed [19].

Other interactions of SLC14A1

• A cDNA clone (HUT2) sharing 61.1% and 89.9% sequence identity with the human erythroid (HUT11) and the rabbit (UT2) urea transporters, respectively, was isolated by homology cloning from a human kidney library [20].
• In addition, immunochemical analysis of red blood cells demonstrated that hUT-B1 also exhibits ABO determinants attached to the single N-linked sugar chain at Asn-211 [14].

Analytical, diagnostic and therapeutic context of SLC14A1

• Expression of a UT-B 2-kb mRNA transcript and of approximately 50- and approximately 98-kDa UT-B proteins is detected in human colonic mucosa by Northern and Western blot analysis [17].
• By in situ hybridization, the gene encoding HUT2 has been assigned to chromosome 18q12.1-q21-1, as found previously for the Kidd/urea transporter HUT11, suggesting that both genes evolved from duplication of a common ancestor [20].
• After confirmation of the JK gene polymorphism we developed a rapid and robust technique for JK genotyping with allele-specific primers in a single-tube PCR [13].
• Immunocytochemistry confirmed that the location of UT-B1 is restricted to descending vasa recta [21].
• Immunoblotting with a polyclonal antibody against the C-ter sequence of rat UT-B1 revealed UT-B1 as both nonglycosylated (29 kDa) and N-glycosylated (47.5 and 33 kDa) proteins in RBC membranes, kidney medulla, brain, and bladder in rat [21].

References