ABCA8

Abstract: Introduction The ATP-binding cassette (ABC) gene superfamily encodes a series of transporter proteins that move a wide variety of substances across extra- and intracellular membranes. Forty-eight known human ABC genes can be divided into seven phylogenetically distinct subfamilies. The ABCA gene subfamily is found exclusively in multicellular eukaryotes. Results We report here on a unique tandem array of five ABCA genes on chromosome 17q24 defining a phylogenetically distinct group. This is the largest cluster of mammalian ABC genes described to date. They are arranged head-to-tail and have similar intron/exon organization in both mouse and human. Northern analysis reveals a heterogeneous pattern of expression in human tissues, with ABCA5 and ABCA10 expressed in skeletal muscle, ABCA6 in the liver, ABCA9 in the heart, and ABCA8 in ovaries. This suggests that these proteins have distinct functions.

Abstract: The ATP-binding cassette (ABC) transporter A subfamily 8 (ABCA8) belongs to the ABCA6-like transporters subgroup, which is distinct from the ABCA1-like subgroup in the ABCA family. The expression and function of the short-size human ABCA8 lacking one of the two ATP-binding domains for ATP hydrolysis, which are regularly present in the other ABCA transporters, have been reported. However, the functional differences between the short-size human ABCA8 and full-size human ABCA8, which has the two ATP-binding domains, remain unknown. The purpose of the present study was to clarify the tissue expression profiles of ABCA6-like and ABCA1-like subgroup transporters and the functional characteristics of ABCA8 in mouse and human. The tissue distribution of mouse ABCA (mABCA) transporter protein and the changes in mABCA8 protein expression levels in a mouse model of obstructive cholestasis were elucidated by means of quantitative targeted absolute proteomics (QTAP). The transport characteristics were clarified in a H...

Abstract: The invention discloses a group of genes for molecular subtyping of renal cell carcinoma and an application of the genes. The group of genes include 44 genes as follows: RHCG gene, RNF128 gene, TMEM255A gene, PCP4 gene, DHRS2 gene, CLDN8 gene, AQP6 gene, SLC18A2 gene, KRT7 gene, SERPINA5 gene, SFTPB gene, DEFB1 gene, MAL gene, ANGPTL4 gene, LCN2 gene, PLIN2 gene, ZNF395 gene, TACSTD2 gene, NDUFA4L2 gene, NNMT gene, HILPDA gene, UMOD gene, SLC12A1 gene, CALB1 gene, C7 gene, S100A2 gene, ASS1 gene, MT1G gene, ABCA8 gene, FOSB gene, MAOB gene, STAP1 gene, TFPI2 gene, AKR1C2 gene, IGFBP6 gene, VCAN gene, FLRT3 gene, MMP7 gene, GSTA1 gene, CRYAB gene, PAH gene, IGFBP1 gene, ATP6V0A4 gene and ALDOB gene. Based upon verification, it is proved that the genes can be used for accurately distinguishing oncocytic adenom, clear cell carcinoma, papillary cell carcinoma chromophobe renal carcinoma; the genes are broad in application scope, high in accuracy rate and short in experimental cycle; and the genes can achieve an important clinical significance for the precise treatment of a patient.

Abstract: ATP binding cassette (ABC) transporters are membrane proteins that are widely distributed in prokaryotes and eukaryotes, and most of them transport substrates across membranes (10, 12, 35). In general, they transport drugs, toxins, peptides, lipid derivatives, and so on, coupled with ATP hydrolysis at their nucleotide binding domains (NBDs) (12). NBDs are characterized by three motifs, Walker A, B, and C (signature) (35). In humans and rodents, ABC transporters are divided into seven subfamilies, A to G, and some of them are known to participate in physiological phenomena. In particular, subfamily A of ABC transporters is an interesting group that includes 13 members found in humans; some members of this group are known to transport lipids and their derivatives and to be related to genetic diseases (8). For example, ABCA1 has been reported to participate in cholesterol trafficking (18, 22), and a genetic defect of it causes Tangier disease, which is characterized clinically by the accumulation of cholesteryl ester in various tissues (9). ABCA1 is also involved in the engulfment of apoptotic cells by macrophages (17). ABCA4 (3, 13) is specifically expressed in the retina and transports N-retinylidene-phosphatidyl-ethanolamine (37), and a genetic defect of it causes Stargardt disease, which is clinically characterized by the progressive loss of central vision and progressive atrophy of the retinal pigment epithelium overlying the macula (1). These examples indicate that the physiological roles of subfamily A members are likely to differ from those of other ABC transporters, such as MDR1, for which knockout mice did not exhibit remarkable abnormalities without the administration of drugs and toxins (29). However, the functions and substrates have been determined for only two members of subfamily A. In order to determine the physiological roles of ABC proteins in the brain or their neuron-specific functions, we tried to identify a novel member of subfamily A in newborn mouse brain and neural cells derived from P19 cells by reverse transcription (RT)-PCR. As a result of full-length cDNA cloning, we found an orthologue of human ABCA5 (mABCA5). The human and rat ABCA5 cDNA have already been isolated, and their mRNAs have been reported to be expressed mainly in brain, lung, and testis (23). The human ABCA5 gene is located on chromosome 17q23.4 and forms a gene cluster with ABCA6, ABCA8, ABCA9, and ABCA10 (10). Similar gene clustering has been found on mouse chromosome 11 (2). However, further characterization of the ABCA5 protein has not been reported. In this study, we determined the subcellular localization of the ABCA5 protein and examined its functions after generating knockout mice.