The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ANXA1  -  annexin A1

Homo sapiens

Synonyms: ANX1, Annexin A1, Annexin I, Annexin-1, Calpactin II, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ANXA1


High impact information on ANXA1

  • Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci [4].
  • The p35 protein from baculoviruses effectively prevents apoptosis by its broad-spectrum caspase inhibition [5].
  • The repositioning of the amino terminus of p35 into the active site of the caspase eliminates solvent accessibility of the catalytic dyad [5].
  • This may be crucial for preventing hydrolysis of the thioester intermediate, which is supported by the abrogation of inhibitory activity through mutations at the N terminus of p35 [5].
  • Here we report the crystal structure of p35 in complex with human caspase-8 at 3.0 A resolution, and biochemical and mutagenesis studies based on the structural information [5].

Chemical compound and disease context of ANXA1

  • The product of the baculovirus p35 gene is a specific inhibitor of a class of cysteine proteases termed caspases, and naturally functions in infected insects [6].
  • Recent studies using the cytochrome P-450 prodrug cyclophosphamide exemplify how the antiapoptotic, caspase-inhibitory baculovirus protein p35 can be combined with P-450 gene-directed enzyme prodrug therapy to prolong localized, intratumoral production of cytotoxic drug metabolites without inducing tumor cell drug resistance [7].
  • L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine [8].
  • Using SDS polyacrylamide gel electrophoresis (SDS-PAGE), several coworkers isolated a unique membrane protein that they named p35 from hairy cells of white patients with hairy cell leukemia [9].
  • Based on evidence that corticosteroids exert their anti-inflammatory action via de novo synthesis of phospholipase A2 inhibitory proteins called lipocortins, we examined effects of high dose dexamethasone and recombinant human lipocortin-1 (annexin-I) on cold-injury brain edema in the rat [10].

Biological context of ANXA1


Anatomical context of ANXA1

  • These data strongly support the notion that ANXA1 critically interferes with a leukocyte endothelial step essential for U937 cell, and possibly monocyte, transmigration both in vitro and in vivo [1].
  • By using rapid subtraction hybridization we studied the effects of human recombinant ANXA1 and the N-terminal ANXA1 peptide on gene expression in a human larynx cell line [11].
  • It is now emerging that ANXA1 is endowed with other roles, since the protein is abundant in inflammatory exudates as it is produced and released by the extravasated neutrophil [13].
  • Annexin 1 (ANXA1) is the first characterized member of the annexin family of proteins able to bind (i.e. to annex) to cellular membranes in a calcium-dependent manner [14].
  • Additionally, we used brefeldin A to investigate the involvement of the classical endoplasmic reticulum (ER)-Golgi pathway of protein secretion in the release of ANXA1 [15].

Associations of ANXA1 with chemical compounds

  • Endogenous production by PBMC of cell surface-associated and intracellular ANXA1 in response to PHA, Der p and PPD in the presence and absence of dexamethasone was measured by specific ELISA [12].
  • Two ANXA1-derived peptides, Ac2-26 and AF-2 (5-500 microM), were assessed for possible inhibition of PHA-and antigen-induced T cell proliferation (measured by 3H-thymidine uptake), while Ac2-26 was assessed for inhibition of Der p-induced interleukin (IL)-5 release and PPD-induced interferon-gamma (IFN-gamma) release (measured by ELISA) [12].
  • Originally described as a phospholipase A2 (PLA2)-inhibitory protein, ANXA1 can affect many components of the inflammatory reaction besides the metabolism of arachidonic acid [14].
  • The GC receptor antagonist, RU486, neither reverted the Dex-dependent ANXA1 secretion nor inhibited the increase of the [Ca2+]i induced by Dex [15].
  • Furthermore, the Ca2+ ionophore, ionomycin, alone induced ANXA1 cleavage, but not its secretion [15].

Physical interactions of ANXA1


Regulatory relationships of ANXA1


Other interactions of ANXA1


Analytical, diagnostic and therapeutic context of ANXA1

  • METHODS: Complementary reverse transcription-polymerase chain reaction and Western blot assays were performed to study the effect of E2beta on the expression of mRNA and protein ANXA1, respectively [2].
  • MEASUREMENTS: The tissue was processed for analysis of ANXA1 mRNA and protein expression by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis and immunogold electron-microscopic histochemistry [3].
  • ANXA1 expression was also analyzed by immunohistochemistry in paraffin-embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions [21].
  • Well-differentiated tumors presented a positive ANXA1 signal in highly keratinized areas whereas moderately and poorly differentiated tumors exhibited very weak or negative staining [21].
  • To address this hypothesis, we examined ANXA1-dependent glucocorticoid actions in co-cultures of murine corticotroph (AtT20 clone D1) and folliculo-stellate (TtT/GF) cell lines [22].


  1. Annexin 1 modulates monocyte-endothelial cell interaction in vitro and cell migration in vivo in the human SCID mouse transplantation model. Perretti, M., Ingegnoli, F., Wheller, S.K., Blades, M.C., Solito, E., Pitzalis, C. J. Immunol. (2002) [Pubmed]
  2. 17beta-estradiol promotes the synthesis and the secretion of annexin I in the CCRF-CEM human cell line. Castro-Caldas, M., Duarte, C.B., Carvalho, A.R., Lopes, M.C. Mediators of inflammation. (2001) [Pubmed]
  3. Expression, subcellular localization and phosphorylation status of annexins 1 and 5 in human pituitary adenomas and a growth hormone-secreting carcinoma. Mulla, A., Christian, H.C., Solito, E., Mendoza, N., Morris, J.F., Buckingham, J.C. Clin. Endocrinol. (Oxf) (2004) [Pubmed]
  4. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Perretti, M., Chiang, N., La, M., Fierro, I.M., Marullo, S., Getting, S.J., Solito, E., Serhan, C.N. Nat. Med. (2002) [Pubmed]
  5. Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex. Xu, G., Cirilli, M., Huang, Y., Rich, R.L., Myszka, D.G., Wu, H. Nature (2001) [Pubmed]
  6. Expression of the antiapoptotic baculovirus p35 gene in tomato blocks programmed cell death and provides broad-spectrum resistance to disease. Lincoln, J.E., Richael, C., Overduin, B., Smith, K., Bostock, R., Gilchrist, D.G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Harnessing apoptosis for improved anticancer gene therapy. Waxman, D.J., Schwartz, P.S. Cancer Res. (2003) [Pubmed]
  8. Monoclonal antibodies specific to a Ca2(+)-bound form of lipocortin I distinguish its Ca2(+)-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2. Hayashi, H., Owada, M.K., Sonobe, S., Domae, K., Yamanouchi, T., Kakunaga, T., Kitajima, Y., Yaoita, H. Biochem. J. (1990) [Pubmed]
  9. Demonstration of p35 in hairy cell leukemia of Japanese patients. Katayama, I., Shibuya, A., Niikawa, K., Nanba, K., Koga, T., Toyama, K. Cancer (1984) [Pubmed]
  10. Lipocortin-1 fails to ameliorate cold-injury brain edema in the rat. Mima, T., Shigeno, T. Acta Neurochir. Suppl. (2000) [Pubmed]
  11. In vitro and in vivo studies on CCR10 regulation by Annexin A1. Rodrigues-Lisoni, F.C., Mehet, D.K., Mehemet, D.K., Peitl, P., John, C.D., da Silva Júnior, W.A., Tajara, E., Buckingham, J.C., Solito, E. FEBS Lett. (2006) [Pubmed]
  12. An annexin 1 (ANXA1)-derived peptide inhibits prototype antigen-driven human T cell Th1 and Th2 responses in vitro. Kamal, A.M., Smith, S.F., De Silva Wijayasinghe, M., Solito, E., Corrigan, C.J. Clin. Exp. Allergy (2001) [Pubmed]
  13. Annexin 1 and neutrophil apoptosis. Perretti, M., Solito, E. Biochem. Soc. Trans. (2004) [Pubmed]
  14. Annexin 1: more than an anti-phospholipase protein. Parente, L., Solito, E. Inflamm. Res. (2004) [Pubmed]
  15. Dexamethasone induces the secretion of annexin I in immature lymphoblastic cells by a calcium-dependent mechanism. Castro-Caldas, M., Duarte, C.B., Carvalho, A.P., Lopes, M.C. Mol. Cell. Biochem. (2002) [Pubmed]
  16. Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation. Goulding, N.J., Euzger, H.S., Butt, S.K., Perretti, M. Inflamm. Res. (1998) [Pubmed]
  17. Mutation finding in patients with dysferlin deficiency and role of the dysferlin interacting proteins annexin A1 and A2 in muscular dystrophies. Cagliani, R., Magri, F., Toscano, A., Merlini, L., Fortunato, F., Lamperti, C., Rodolico, C., Prelle, A., Sironi, M., Aguennouz, M., Ciscato, P., Uncini, A., Moggio, M., Bresolin, N., Comi, G.P. Hum. Mutat. (2005) [Pubmed]
  18. Epidermal-growth-factor-stimulated phosphorylation of calpactin II in membrane vesicles shed from cultured A-431 cells. Blay, J., Valentine-Braun, K.A., Northup, J.K., Hollenberg, M.D. Biochem. J. (1989) [Pubmed]
  19. Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5. Guzmán-Aránguez, A., Olmo, N., Turnay, J., Lecona, E., Pérez-Ramos, P., López de Silanes, I., Lizarbe, M.A. J. Cell. Biochem. (2005) [Pubmed]
  20. Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. Hayhoe, R.P., Kamal, A.M., Solito, E., Flower, R.J., Cooper, D., Perretti, M. Blood (2006) [Pubmed]
  21. Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status. Garcia Pedrero, J.M., Fernandez, M.P., Morgan, R.O., Herrero Zapatero, A., Gonzalez, M.V., Suarez Nieto, C., Rodrigo, J.P. Am. J. Pathol. (2004) [Pubmed]
  22. Evidence from studies on co-cultures of TtT/GF and AtT20 cells that Annexin 1 acts as a paracrine or juxtacrine mediator of the early inhibitory effects of glucocorticoids on ACTH release. Tierney, T., Christian, H.C., Morris, J.F., Solito, E., Buckingham, J.C. J. Neuroendocrinol. (2003) [Pubmed]
WikiGenes - Universities