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Gene Review

Anxa6  -  annexin A6

Mus musculus

Synonyms: 67 kDa calelectrin, AW107198, Annexin A6, Annexin VI, Annexin-6, ...
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Disease relevance of Anxa6


High impact information on Anxa6

  • Because of interest in the role of annexin VI in cardiovascular function, we examined heart rate and blood pressure in knockout and wild-type mice and found these to be identical in the two groups [6].
  • However, P70 and hsp70 are unique proteins on the basis of peptide map analysis and are regulated differently in germ cells [7].
  • Labeling studies showed that P70 was synthesized primarily in pachytene spermatocytes and that little synthesis occurred in round spermatids or in preleptotene and leptotene-zygotene stages of spermatogenesis [8].
  • Unstressed preleptotene and leptotene-zygotene spermatocytes contained little P70, whereas relatively large amounts of P70 were present in pachytene spermatocytes and round spermatids [8].
  • When hsp70 from spermatogenic cells is heat induced, it migrates to the same location as does P70 on two-dimensional polyacrylamide gels, indicating that it has an apparently identical mass and isoelectric point [7].

Biological context of Anxa6

  • Cell surface annexin VI is involved in (125)I-TGF-beta(1) and (125)I-alpha(2)M(*) binding to the acidic pH binding sites and (125)I-alpha(2)M(*) binding to LRP-1 at neutral pH as demonstrated by the sensitivity of cells to pretreatment with anti-annexin VI IgG [9].
  • Anti-annexin VI antibodies inhibited the adhesion of RAW117 cells to fixed or unfixed murine hepatic sinusoidal endothelial cells by approximately 40%, indicating a role for annexin VI in mediating a portion of the Ca(2+)-dependent RAW117 cell adhesion to target liver microvessel endothelial cells [1].
  • The localization of Anx-6 and Glr-1 extends the known synteny homology between human chromosome 5q21-q31 and mouse Chr 11 and reveals the probable chromosomal location of the human counterpart to spd [10].
  • The presence of normal Anx-6 and Glr-1 mRNA transcripts was confirmed by Northern blot analysis, in situ hybridization, and DNA sequence analysis [10].
  • These results indicate that P70 is expressed in a stage-specific manner during cell differentiation, whereas hsp70 is synthesized in response to stress in all populations of isolated spermatogenic cells examined [8].

Anatomical context of Anxa6

  • This is evidenced by: 1) structural and Western blot analyses of the protein purified from bovine liver plasma membranes by alpha(2)M(*) affinity column chromatography at acidic pH, and 2) dot blot analysis of the interaction of annexin VI and (125)I-alpha(2)M(*) [9].
  • Immunoreactivity for the endonexins (annexins IV and V) was found in the palatal epithelium and mesenchyme, whereas immunoreactivity for the 67-kDa calelectrin (annexin VI) was found only in the mesenchyme [11].
  • In the present study we identified the 70-kDa cell surface component that binds to hepatic sinusoidal endothelial cells in a Ca(2+)-dependent manner as annexin VI [1].
  • Annexin A6 is the most abundant annexin in the heart, and has been localized in various cell types including myocytes [12].
  • Ab-MLV strains expressing P70/S2 failed to transform NIH 3T3 cells and demonstrated a greatly reduced capacity to mediate signaling events associated with the Ras-dependent mitogen-activated protein (MAP) kinase pathway [13].

Associations of Anxa6 with chemical compounds

  • Cytofluorographic analysis indicated that annexin VI was expressed on the cell surface in slightly higher amounts on highly metastatic RAW117 cells, and it was not removable by EDTA treatment [1].
  • We have previously detected a number of protein kinase C (PKC) alpha-binding proteins in skeletal muscle cytosol by blot overlay assay, and now identify the major, 69 kDa binding protein as annexin VI by immunoblotting and overlay assay of hydroxyapatite chromatography fractions [14].
  • The C3 antibody reacted with P70 isoforms in rat, human, mouse, guinea pig, boar, and rooster testicular homogenates [3].
  • Because this protein had the ability to bind phospholipids such as phosphatidylserine, phosphatidylinositol, and cardiolipin in the presence of Ca2+, this protein was designated as calphobindin II (CPB-II) [15].

Other interactions of Anxa6


Analytical, diagnostic and therapeutic context of Anxa6

  • Cell surface annexin VI is also capable of mediating internalization and degradation of cell surface-bound (125)I-TGF-beta(1) and (125)I-alpha(2)M(*) at pH 6 and of forming ternary complexes with (125)I-alpha(2)M(*) and LRP-1 at neutral pH as demonstrated by co-immunoprecipitation [9].
  • The steady-state isoform ratio of the annexin VI protein is consistent with the RT-PCR data [16].
  • Purified annexin VI migrates as a closely spaced doublet when separated by SDS-PAGE [16].
  • Immunohistochemistry of human melanoma specimens with this antiserum revealed a decrease or loss of Annexin VI expression as melanomas progressed from a benign to a more malignant phenotype [2].


  1. Extracellular annexin VI expression is associated with divalent cation-dependent endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. Tressler, R.J., Yeatman, T., Nicolson, G.L. Exp. Cell Res. (1994) [Pubmed]
  2. Identification by differential display of annexin-VI, a gene differentially expressed during melanoma progression. Francia, G., Mitchell, S.D., Moss, S.E., Hanby, A.M., Marshall, J.F., Hart, I.R. Cancer Res. (1996) [Pubmed]
  3. Characterization of the heat shock protein P70 in rat spermatogenic cells. Raab, L.S., Polakoski, K.L., Hancock, L.W., Hamilton, D.W. Mol. Reprod. Dev. (1995) [Pubmed]
  4. Detection of parvovirus B19-specific IgM by antibody capture radioimmunoassay. Cohen, B.J. J. Virol. Methods (1997) [Pubmed]
  5. Annexin VI modulates Ca2+ and K+ conductances of spinal cord and dorsal root ganglion neurons. Naciff, J.M., Behbehani, M.M., Kaetzel, M.A., Dedman, J.R. Am. J. Physiol. (1996) [Pubmed]
  6. Immunological development and cardiovascular function are normal in annexin VI null mutant mice. Hawkins, T.E., Roes, J., Rees, D., Monkhouse, J., Moss, S.E. Mol. Cell. Biol. (1999) [Pubmed]
  7. A novel hsp70-like protein (P70) is present in mouse spermatogenic cells. Allen, R.L., O'Brien, D.A., Eddy, E.M. Mol. Cell. Biol. (1988) [Pubmed]
  8. Expression of heat shock proteins by isolated mouse spermatogenic cells. Allen, R.L., O'Brien, D.A., Jones, C.C., Rockett, D.L., Eddy, E.M. Mol. Cell. Biol. (1988) [Pubmed]
  9. Identification and characterization of the acidic pH binding sites for growth regulatory ligands of low density lipoprotein receptor-related protein-1. Ling, T.Y., Chen, C.L., Huang, Y.H., Liu, I.H., Huang, S.S., Huang, J.S. J. Biol. Chem. (2004) [Pubmed]
  10. Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response. Buckwalter, M.S., Testa, C.M., Noebels, J.L., Camper, S.A. Genomics (1993) [Pubmed]
  11. Developmental regulation of various annexins in the embryonic palate of the mouse: dexamethasone affects expression of annexin-1. Chepenik, K.P., Shipman-Appasamy, P., Ahn, N., Goldowitz, D. J. Craniofac. Genet. Dev. Biol. (1995) [Pubmed]
  12. Annexins and Ca2+ handling in the heart. Camors, E., Monceau, V., Charlemagne, D. Cardiovasc. Res. (2005) [Pubmed]
  13. The carboxyl terminus of v-Abl protein can augment SH2 domain function. Warren, D., Heilpern, A.J., Berg, K., Rosenberg, N. J. Virol. (2000) [Pubmed]
  14. Activated protein kinase C alpha associates with annexin VI from skeletal muscle. Schmitz-Peiffer, C., Browne, C.L., Walker, J.H., Biden, T.J. Biochem. J. (1998) [Pubmed]
  15. Isolation and characterization of an anticoagulant protein from human placenta. Yoshizaki, H., Arai, K., Mizoguchi, T., Shiratsuchi, M., Hattori, Y., Nagoya, T., Shidara, Y., Maki, M. J. Biochem. (1989) [Pubmed]
  16. Annexin VI isoforms are differentially expressed in mammalian tissues. Kaetzel, M.A., Pula, G., Campos, B., Uhrin, P., Horseman, N., Dedman, J.R. Biochim. Biophys. Acta (1994) [Pubmed]
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