Structure of the human annexin VI gene.

Abstract

We report the structure of the human annexin VI gene and compare the intron-exon organization with the known structures of the human annexin I and II genes. The gene is -60 kbp long and contains 26 exons. Consistent with the published annexin VI cDNA sequence, the genomic sequence at the 3' end does not contain a canonical polyadenylylation signal. The genomic sequence upstream of the transcription start site contains TATAA and CAAT motifs. The spatial organization of the exons does not reveal any obvious similarities between the two halves of the annexin VI gene. Comparison of the intron-exon boundary positions of the annexin VI gene with those of annexins I and U reveals that within the repeated domains the break points are perfectly conserved except for exon 8, which is one codon smaller in annexin H. The corresponding point in the second half of annexin VI is represented by two exons, exons 20 and 21. The latter exon is alternatively spliced, giving rise to two annexin VI isoforms that differ with respect to a 6-amino acid insertion at the start of repeat 7.

Novel Human and Mouse Annexin A10 Are Linked to the Genome Duplications during Early Chordate Evolution

“…The representation of vertebrate annexins in fish and their apparent absence from invertebrates indicate that duplication among these structurally related genes may have coincided with the proposed chromosomal duplications (Lundin, 1993;Holland et al, 1994) during early chordate radiation more than 500 -600 Mya (Kumar and Hedges, 1998). The phylogenetic confirmation of direct ancestry between ANXA5 and 5Ј-ANXA6 (Rodriguez-Garcia et al, 1999) with congruent gene structures (Fernandez et al, 1994;Smith et al, 1994) and between ANXA10 and 3Ј-ANXA6 (Fig. 4) with a rare codon deletion at the same location provides crucial evidence for these paralogous relationships.…”

“…4) indicate that these were comparatively recent gene duplication events, in contrast to the more distant common ancestor of the 5Ј and 3Ј tetrads comprising annexin A6. If annexin A6 was the ancient product of tandem duplication and fusion of a solitary tetrad, as originally proposed (Smith et al, 1994), then at some later date(s) the 5Ј and 3Ј components of this octad annexin must have given rise to two unique tetrad annexins, A5 and A10, at separate locations on present-day human chromosome 4. Although feasible, the structural disparity between such an octad progenitor and tetrad descendents, the genetic segregation of the latter, and the apparent absence of concerted evolution between the two halves of annexin A6 are difficult to reconcile.…”

“…ity was first realized when the 5Ј tetrad of the annexin A6 octad on human chromosome 5 was found to be more closely related to annexin A5 on chromosome 4 than it was to its tandemly fused 3Ј homologue (Rodriguez-Garcia et al, 1999). If annexin A6 was not formed by tandem duplication and fusion of a unique tetrad annexin as originally proposed (Smith et al, 1994), then a tetrad progenitor corresponding to the 3Ј half should also exist, assuming it was not silenced or physically integrated as the 3Ј component. We present molecular, genetic, and phylogenetic evidence for such a novel tetrad annexin and examine its possible involvement in vertebrate chromosomal evolution that may have led to the creation of annexin A6.…”

Transcriptional map of the Treacher Collins candidate gene region.

“…Individual exon clones were confirmed to be contained within the relevant cosmids by Southern blot hybridization. After BLASTN and BLASTX computer searches, five clones were found to correspond to previously characterized genes, three of which (all from cosmid 2F) were identified as exons 14, 15, and 16 of ANX6 (Smith et al 1994). Cosmid 2F is the distal most cosmid of contig III and was known previously to contain the 3'-untranslated region of ANX6 (Crompton et al 1988).…”

Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption

“…Evolutionarily, annexin A6 has been speculated to have arisen from a gene-duplication event combining annexins A5 and A10. 25,26 The four amino-terminal annexin domains are highly homologous to annexins A1 and A2. 20 Annexin A6 may be involved in muscle membrane repair in zebrafish and mouse skeletal muscle.…”