Alternative titles; symbols
HGNC Approved Gene Symbol: ANXA6
Cytogenetic location: 5q33.1 Genomic coordinates (GRCh38): 5:151,100,706-151,157,779 (from NCBI)
ANXA6 is a member of a family of proteins that bind membrane or cytoskeleton in a Ca(2+)-dependent manner. These proteins are characterized by homologous amino acid sequences that are present in multiple copies in each protein. The family is variously known as calelectrins, annexins, calpactins, endonexins, and lipocortins.
Three members of the calelectrin family with apparent molecular masses of 67 kD, 35 kD, and 32.5 kD had been purified to homogeneity. Sudhof et al. (1988) reported the cDNA cloning and primary structure of human 67-kD calelectrin. The deduced sequence contains 8 similar repeats, each consisting of about 68 amino acids. Comparison of the 67-kD calelectrin sequence with the protein sequences of lipocortins I and II (151690, 151740) demonstrated a close relationship (42 to 45% identity).
Thomas et al. (2002) found that Anxa6 showed a punctate supranuclear and apical distribution in rat pancreatic acinary cells. Anxa6 colocalized with Crhsp28, a component of a protein complex associated with vesicular structures.
Davies et al. (1989) assigned the ANXA6 gene to 5q32-q34 by use of a cDNA clone to probe genomic DNA from rodent-human somatic cell hybrids and for in situ hybridization. The corresponding gene in the mouse was assigned to chromosome 11 by probing DNA from rodent-rodent somatic cell hybrids. Warrington and Bengtsson (1994) used 3 physical mapping methods (radiation hybrid mapping, pulsed field gel electrophoresis, and fluorescence in situ hybridization of interphase nuclei) to determine the order and relative distances between 12 loci in the 5q31-q33 region. ANXA6 was one of those loci.
Smith et al. (1994) demonstrated that the ANX6 gene is approximately 60 kb long and contains 26 exons. The genomic sequence at the 3-prime 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 revealed no obvious similarities between the 2 halves of the ANX6 gene. Comparison of the intron/exon boundary positions of ANX6 with those of ANX1 (151690) and ANX2 (151740) revealed that within the repeated domains the breakpoints are perfectly conserved except for exon 8, which is 1 codon smaller in ANX2. The corresponding point in the second half of ANX6 is represented by 2 exons, exons 20 and 21. The latter exon is alternatively spliced, giving rise to annexin VI isoforms that differ with respect to a 6-amino acid insertion at the start of repeat 7.
Thomas et al. (2002) found that stimulation of rat pancreatic acinary cells with the secretagogue cholecystokinin (118440) enhanced the colocalization of Anxa6 and Crhsp28 within regions of acini immediately below the apical plasma membrane. Thomas et al. (2002) concluded that Ca(2+)-dependent binding between CRHSP28 and ANXA6 is required for acinar cell membrane trafficking events and digestive enzyme secretion.
Davies, A. A., Moss, S. E., Crompton, M. R., Jones, T. A., Spurr, N. K., Sheer, D., Kozak, C., Crumpton, M. J. The gene coding for the p68 calcium-binding protein is localized to bands q32-q34 of human chromosome 5, and to mouse chromosome 11. Hum. Genet. 82: 234-238, 1989. [PubMed: 2731935] [Full Text: https://doi.org/10.1007/BF00291161]
Smith, P. D., Davies, A., Crumpton, M. J., Moss, S. E. Structure of the human annexin VI gene. Proc. Nat. Acad. Sci. 91: 2713-2717, 1994. [PubMed: 8146179] [Full Text: https://doi.org/10.1073/pnas.91.7.2713]
Sudhof, T. C., Slaughter, C. A., Leznicki, I., Barjon, P., Reynolds, G. A. Human 67-kDa calelectrin contains a duplication of four repeats found in 35-kDa lipocortins. Proc. Nat. Acad. Sci. 85: 664-668, 1988. [PubMed: 2963335] [Full Text: https://doi.org/10.1073/pnas.85.3.664]
Thomas, D. D. H., Kaspar, K. M., Taft, W. B., Weng, N., Rodenkirch, L. A., Groblewski, G. E. Identification of annexin VI as a Ca(2+)-sensitive CRHSP-28-binding protein in pancreatic acinar cells. J. Biol. Chem. 277: 35496-35502, 2002. [PubMed: 12105190] [Full Text: https://doi.org/10.1074/jbc.M110917200]
Warrington, J. A., Bengtsson, U. High-resolution physical mapping of human 5q31-q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis. Genomics 24: 395-398, 1994. [PubMed: 7698768] [Full Text: https://doi.org/10.1006/geno.1994.1636]