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Gene Review

ANXA2  -  annexin A2

Gallus gallus

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High impact information on ANXA2

  • Here we have characterized the p11 binding site on p36 by fluorescence spectroscopy using porcine p36 labelled at cysteine 8 with the fluorophore Prodan (6-proprionyl-2-dimethylamino-naphthalene) [1].
  • p36, the major cytoplasmic substrate of src tyrosine protein kinase, binds to its p11 regulatory subunit via a short amino-terminal amphiphatic helix [1].
  • The major cytoplasmic target of various tyrosine-specific protein kinases is a 36-kd protein (p36) [2].
  • By comparison B-lymphocytes lacking annexin 2 (Anx2) showed no such resistance, providing evidence that this effect is specific to loss of Anx5 [3].
  • Types II and X collagen only bound to liposomes in the presence of annexin V but not in the presence of annexin II or VI [4].

Biological context of ANXA2

  • We have used peptides of differing length from the amino-terminal domain of p36 to restrict the major binding site to the first 12 residues [1].
  • This apposition is in line with biochemical experiments indicating an influence of core ligands on tyrosine phosphorylation and an enhanced Ca2+ requirement of the modified p36 in phospholipid binding [5].
  • Phosphorylation of p36 (the calpactin I heavy chain) was drastically reduced in cells expressing SRX5 src, suggesting that the phenotype of SRX5 results from an alteration in substrate recognition by the src kinase [6].
  • There was no cross-reaction with antibodies to the C- or N-terminus of annexin II [7].
  • Sequence homologies between p36, the substrate of pp60src tyrosine kinase and a 67 kDa protein isolated from bovine aorta [8].

Anatomical context of ANXA2


Associations of ANXA2 with chemical compounds

  • Interestingly the N-terminal acetyl group of p36 forms a functional part of the p11 binding site [1].
  • The annexin Ca(2+) channel blocker, K-201, not only inhibited Ca(2+) influx into fura-2-loaded PS-enriched liposomes mediated by annexin II, V, or VI, but also inhibited Ca(2+) uptake by authentic MV [4].
  • Glycerol gradient analysis suggested the presence of more than one type of complex: one containing p115, p68c-rel, p59v-rel, and p36, and another containing p124, p115, p59v-rel, and possibly p68c-rel [12].
  • The kinase activity of pp60v-src-L was indistinguishable from that of the wild type in chicken cells but was significantly reduced in rat cells as assayed by an in vitro immune complex assay; in vivo phosphorylation of one specific substrate, p36 (calpactin I heavy chain); and total phosphotyrosine-containing proteins [13].
  • The existence of a single tryptophan residue in the protein p36, a member of a recently characterized family of Ca2+ binding proteins called annexins, is exploited to provide unique spectroscopic information on the annexin repeat motif and its role in Ca2+ binding [14].

Other interactions of ANXA2

  • However, antibodies against calpactin I (lipocortin II), calpactin II (lipocortin I), 35-kDa calcimedin, and 67-kDa calcimedin did not cross-react with 32-kDa calcimedin [15].
  • Computer aided homology analysis revealed that calgizzarin exhibits a 43.2% homology to S-100 alpha, 38.6% to S-100 beta and 40.0% to annexin II light chain, p10 [16].

Analytical, diagnostic and therapeutic context of ANXA2

  • We have established the relationship between p36 and p40 by molecular cloning of cDNAs that encode both proteins and have determined that they are the products of a single gene [9].
  • Sequence analysis shows that 67 kDa bovine aorta protein shares common domains with p36 and possesses the consensus aminoacid sequences of mammalian Ca2+-dependent membrane-binding protein and p36/gelsolin [8].


  1. p36, the major cytoplasmic substrate of src tyrosine protein kinase, binds to its p11 regulatory subunit via a short amino-terminal amphiphatic helix. Johnsson, N., Marriott, G., Weber, K. EMBO J. (1988) [Pubmed]
  2. The regulatory chain in the p36-kd substrate complex of viral tyrosine-specific protein kinases is related in sequence to the S-100 protein of glial cells. Gerke, V., Weber, K. EMBO J. (1985) [Pubmed]
  3. DT40 cells lacking the Ca2+-binding protein annexin 5 are resistant to Ca2+-dependent apoptosis. Hawkins, T.E., Das, D., Young, B., Moss, S.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. The roles of annexins and types II and X collagen in matrix vesicle-mediated mineralization of growth plate cartilage. Kirsch, T., Harrison, G., Golub, E.E., Nah, H.D. J. Biol. Chem. (2000) [Pubmed]
  5. A discontinuous epitope on p36, the major substrate of src tyrosine-protein-kinase, brings the phosphorylation site into the neighbourhood of a consensus sequence for Ca2+/lipid-binding proteins. Johnsson, N., Johnsson, K., Weber, K. FEBS Lett. (1988) [Pubmed]
  6. Host range mutants of v-src: alterations in kinase activity and substrate interactions. Liebl, E.C., England, L.J., DeClue, J.E., Martin, G.S. J. Virol. (1992) [Pubmed]
  7. Evidence for distinct membrane receptors for 1 alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) in osteoblasts. Boyan, B.D., Bonewald, L.F., Sylvia, V.L., Nemere, I., Larsson, D., Norman, A.W., Rosser, J., Dean, D.D., Schwartz, Z. Steroids (2002) [Pubmed]
  8. Sequence homologies between p36, the substrate of pp60src tyrosine kinase and a 67 kDa protein isolated from bovine aorta. Martin, F., Derancourt, J., Capony, J.P., Colote, S., Cavadore, J.C. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  9. Purification and characterization of an alpha-actinin-binding PDZ-LIM protein that is up-regulated during muscle differentiation. Pomiès, P., Macalma, T., Beckerle, M.C. J. Biol. Chem. (1999) [Pubmed]
  10. Establishment of the primary structure of the major lipid-dependent Ca2+ binding proteins of chicken growth plate cartilage matrix vesicles: identity with anchorin CII (annexin V) and annexin II. Genge, B.R., Cao, X., Wu, L.N., Buzzi, W.R., Showman, R.W., Arsenault, A.L., Ishikawa, Y., Wuthier, R.E. J. Bone Miner. Res. (1992) [Pubmed]
  11. pp60src-dependent protein phosphorylation in membranes from Rous sarcoma virus-transformed chicken embryo fibroblasts. Dehazya, P., Martin, G.S. Virology (1985) [Pubmed]
  12. p59v-rel, the transforming protein of reticuloendotheliosis virus, is complexed with at least four other proteins in transformed chicken lymphoid cells. Simek, S., Rice, N.R. J. Virol. (1988) [Pubmed]
  13. A mutation in v-src that removes a single conserved residue in the SH-2 domain of pp60v-src restricts transformation in a host-dependent manner. Verderame, M.F., Kaplan, J.M., Varmus, H.E. J. Virol. (1989) [Pubmed]
  14. Absorption and fluorescence spectroscopic studies of the Ca2(+)-dependent lipid binding protein p36: the annexin repeat as the Ca2+ binding site. Marriott, G., Kirk, W.R., Johnsson, N., Weber, K. Biochemistry (1990) [Pubmed]
  15. Purification, characterization, and partial sequence analysis of 32-kDa calcimedin from chicken gizzard. Kobayashi, R., Hidaka, H., Tashima, Y. Arch. Biochem. Biophys. (1990) [Pubmed]
  16. Molecular cloning and sequencing of a cDNA clone encoding a new calcium binding protein, named calgizzarin, from rabbit lung. Watanabe, M., Ando, Y., Todoroki, H., Minami, H., Hidaka, H. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
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