Identification of 18 Mouse ABC Genes and Characterization of the ABC Superfamily in Mus musculus
ABSTRACT ATP-binding cassette (ABC) genes encode a family of transport proteins known to be involved in a number of human genetic diseases. In this study, we characterized the ABC superfamily in Mus musculus through in silico gene identification and mapping and phylogenetic analysis of mouse and human ABC genes. By querying dbEST with amino acid sequences from the conserved ATP-binding domains, we identified and partially sequenced 18 new mouse ABC genes, bringing the total number of mouse ABC genes to 34. Twelve of the new ABC genes were mapped in the mouse genome to the X chromosome and to 10 of the 19 autosomes. Phylogenetic relationships of mouse and human ABC genes were examined with maximum parsimony and neighbor-joining analyses that demonstrated that mouse and human ABC orthologs are more closely related than are mouse paralogs. The mouse ABC genes could be grouped into the seven previously described human ABC subfamilies. Three mouse ABC genes mapped to regions implicated in cholesterol gallstone susceptibility.
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- "An initial comparison of the lengths of the extracellular loops revealed similarities between MSD1 of CFTR and MSD2 of P-gp and vice versa (Figure S2), and these domains were thus switched during the modeling procedure. Given the low sequence homology between P-gp and CFTR in the MSDs, it is not possible to determine whether this domain switching has evolutionary significance, although the assertion that full-transporters such as CFTR and P-gp may have been independently assembled from ancestral half-transporter genes ,  does not preclude this possibility. "
ABSTRACT: Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), the most common life-shortening genetic disease among Caucasians. Although general features of the structure of CFTR have been predicted from homology models, the conformational changes that result in channel opening and closing have yet to be resolved. We created new closed- and open-state homology models of CFTR, and performed targeted molecular dynamics simulations of the conformational transitions in a channel opening event. The simulations predict a conformational wave that starts at the nucleotide binding domains and ends with the formation of an open conduction pathway. Changes in side-chain interactions are observed in all major domains of the protein, and experimental confirmation was obtained for a novel intra-protein salt bridge that breaks near the end of the transition. The models and simulation add to our understanding of the mechanism of ATP-dependent gating in this disease-relevant ion channel.PLoS ONE 09/2013; 8(9):e74574. DOI:10.1371/journal.pone.0074574 · 3.23 Impact Factor
- JNCI Journal of the National Cancer Institute 11/2000; 92(20):1628-9. DOI:10.1093/jnci/92.20.1628 · 15.16 Impact Factor
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ABSTRACT: throughout the coding region. Abcg3 is most closely related to ABCG2 with 54% amino acid identity overall, 64% in the NBF and 50% in the TM region. The alignment was used to generate a phylogenetic tree of the genes, and this analysis confirms that Abcg3 and ABCG2 are closely related (data not shown). Surprisingly, Abcg3 contains several unusual residues in the Walker A and signature (C) domains. The Walker A consensus is GAGKST, and the Abcg3 sequence is DGSRSL; the C region consensus is LSGG, and the Abcg3 sequence in this region is RSKE. Many of these residues are absolutely conserved in all ABC genes, and mutations in these regions typically lead to non-functional proteins. This suggests that Abcg3 may not bind and/or hydrolyze ATP.Mammalian Genome 12/2000; 12(1):86-88. DOI:10.1007/s003350010237 · 2.88 Impact Factor