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{"project":"2_test","denotations":[{"id":"14723793-9775386-10642188","span":{"begin":1207,"end":1208},"obj":"9775386"},{"id":"14723793-9020585-10642189","span":{"begin":3884,"end":3885},"obj":"9020585"}],"text":"Sequence homology and molecular characteristics\nThe mouse Acdp genes showed very strong homologies of both nucleotide and AA sequences to the human ACDP genes (Table 1). The highest homologies were observed between the human ACDP2 and the mouse Acdp2 gene (91% of nucleotide identity, 97% of AA identity and 99.4% of AA homology). In addition, the 5' UTR nucleotide sequences (20 bp of nucleotides before start codon) also showed high homologies to the human homologs, for example, the Acdp2 5' UTR sequence showed 95% identities to its human homolog. However, the homologies in the 3' UTR sequences (20 bp of nucleotides after stop codon) were much lower (40–55%) for all Acdp genes except Acdp4 (90% identity to its human homolog). The ancient conserved domain (ACD) has 55.3% of AA identity and 83.3% of homology between all mouse and human ACDP proteins (Fig. 2). The ACD domain is evolutionarily conserved in divergent species ranging from bacteria, yeast, C. elegans, D. melanogaster, mouse to human (Fig. 3). Particularly, as shown in Fig. 3, Acdp proteins showed very strong AA homology to bacteria CorC protein (35% AA identity with 55% homology), which is involved in magnesium and cobalt efflux [7]. High AA homology was also observed between the Acdp proteins and the yeast Amip3 protein (35% AA identity with 56% homology). The Amip3 is likely to be a homologous to the bacteria CorC protein. The Amip3 mutants confer resistance to copper toxicity (Personal communication with Dr. V.C. Culotte, John Hopkins Bloomberg, School of Public Health). The evolutionary relationships among those proteins are illustrated by a phylogenetic tree constructed based on the AA homology of proteins (Fig. 4).\nTable 1 Nucleotide and amino acid homologies (%) between human ACDP and mouse Acdp members.\nAcdp Acdp1 Acdp2 Acdp3 Acdp4\nDNA in coding region 89 91 86 87\nAA identity 94 97 86 89\nAA homology 98.8 99.4 94 96\n5' UTR 85 95 80 80\n3' UTR 40 55 50 90\nFigure 2 Amino acid sequence homology alignment for all of the ACDP and Acdp genes within the ACD domain. The sequence data for the Acdp genes have been deposited in GenBank under accession number AF202994 (Acdp1), AF216961 (Acdp2), AF216964 (Acdp3) and AF216963 (Acdp4). Identical amino acids or amino acids with very strong homologies among all proteins were shaded black. Identical amino acids or amino acids with very strong homologies in most of the proteins were shaded grey. Dot lines represent gaps for the alignment.\nFigure 3 Amino acid sequence alignment showing the conservation of ACD domain in various species. Amip3 is a protein from Saccharomyces cerevisiae (NP_014581). CanG is a protein from Candida glabrata (AAF33142). NeuC (EAA31204) is a hypothetical protein from Neurospora crassa. DroM is a gene product from D. melanogaster. The accession number for this gene is CG40084 in BDGP (Berkeley Drosophila Genome Project). AnoG represents a protein from the anopheles gambiae str. (EAA01004). CaeE (AAK77203) is a hypothetical protein from the Caenohabditis elegans. CorC represents bacteria magnesium and cobalt efflux protein from the Shewanella oneidensis. XyFD is a hypothetical protein from the Xylella fastidiosa Dixon (ZP_00038107).\nFigure 4 Phylogenetic tree showing relationships among proteins containing the ACD domain from figure 2 and 3. The phylogenetic tree was constructed according to the calculation of the best match for the selected sequences. Abbreviations for each protein are the same as presented in figure 3. We found that all mouse Acdp members contain four distinct transmembrane domains (Fig. 5), two CBS domains and a DUF21 domain that are found in bacteria CorC and yeast Amip3 proteins. CBS domains are small intracellular modules that are mostly found in 2 or four copies within a protein. Pairs of CBS domains dimerise to form a stable globular domain [8]. DUF21 (CD: pfam01959.9) is a newly defined domain with unknown function. This domain is a transmembrane region and found to be located in the N-terminus of the proteins adjacent to two intracellular CBS domains . A cNMP-binding domain (cyclic nucleotide-monophosphate-binding domain) was found in all Acdp members.\nFigure 5 Four transmembrane domains within Acdp4 protein. Transmembrane domains were predicted by the TMHMM program . The plot shows the posterior probabilities of inside /outside/TM helix. At the top of the plot (between 1 and 1.2) the N-best prediction is shown. The plot is obtained by calculating the total probability that a residue sits in helix, inside, or outside summed over all possible paths through the model. In addition, Acdp1 contains an Alanine-rich region (2–10: AAAAAAAAA), a Leucine-rich region (204–257: LLRVRPRLYGPGGDLLPPAWLRALGALLLLALSALF SGLRLSLLSLDPVELRVL), a Proline-rich region (78–130: PGPPVPAAPVPAPSLA PGENGTGDWAPRLVFIEEPPGAGGAAPSAVPTRPPGP), and two amidation sites (917–920: MGKK; 926–929: SGRK). Acdp2 has a glycine-rich region (201–222: GAGGSGSASGTVGGKGGAGVAG). Acdp3 possesses a large alanine-rich region (2–261) and a large leucine-rich region (201–299). Acdp4 contains a leucine zipper pattern (185–206: LVMVLLVLSGIFSGLNLGLMAL) and an amidation site (7–10: GGRR)."}

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PMC:340383 / 5869-11070 JSONTXT

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PMC:340383 / 5869-11070 JSON TXT