{PDOC00195} {PS00223; ANNEXIN_1} {PS51897; ANNEXIN_2} {BEGIN} **************************************** * Annexin repeat signature and profile * **************************************** Annexins [1 to 8] are a group of calcium-binding proteins that associate reversibly with membranes. They bind to phospholipid bilayers in the presence of micromolar free calcium concentration. The binding is specific for calcium and for acidic phospholipids. Annexins have been claimed to be involved in cytoskeletal interactions, phospholipase inhibition, intracellular signaling, anticoagulation, and membrane fusion. Annexins are widely distributed among eukaryotes but largely absent in prokaryotes and yeast. They are classified according to the evolutionary divisions of the eukaryotes into five families: A (ANXA, vertebrates, including humans), B (ANXB, invertebrates), C (ANXC, fungi), D (ANXD, true plants), E (ANXE, protists). Each of these proteins consist of a unique N-terminal domain followed by four or eight copies (in annexin A6) of a conserved segment of approximately 70 residues. The tertiary structure of annexins is evolutionary conserved; a single molecule resembles a slightly curved disk with the calcium and phospholipid-binding sites located on the more convex surface and the more concave surface facing the cytoplasm. Each single annexin repeat (sometimes known as an 'endonexin fold') is comprised of five alpha-helices(A-E) (see ). Four of them (A, B, D and E) are arranged parallel and form a tightly packed helix-loop-helix bundle. In contrast, helix C is almost perpendicular and covers the remaining four on the surface. Each of the repeats has the potential to have a type II Ca(2+)-binding bipartite motif, located on two different alpha-helices (GxGT-(38-40 residues)-D/E), but typically some of them are non-functional. The core of the helix bundle is composed largely of hydrophobic residues, while hydrophilic residues are exposed on the surface of the protein and between the repeats. The N-terminal domain of variable length, amino acid composition, and determinants of hydrophobicity plays an important role in mediating the interaction of annexins with other intracellular protein partners, such as those of the S100 family cytoplasmic proteins [7,8,9]. The proteins known to belong to the annexin family are listed below: - Annexin I (Lipocortin 1) (Calpactin 2) (p35) (Chromobindin 9). - Annexin II (Lipocortin 2) (Calpactin 1) (Protein I) (p36) (Chromobindin 8). - Annexin III (Lipocortin 3) (PAP-III). - Annexin IV (Lipocortin 4) (Endonexin I) (Protein II) (Chromobindin 4). - Annexin V (Lipocortin 5) (Endonexin 2) (VAC-alpha) (Anchorin CII) (PAP-I). - Annexin VI (Lipocortin 6) (Protein III) (Chromobindin 20) (p68) (p70). This is the only known annexin that contains 8 (instead of 4) repeats. - Annexin VII (Synexin). - Annexin VIII (Vascular anticoagulant-beta) (VAC-beta). - Annexin IX from Drosophila. - Annexin X from Drosophila. - Annexin XI (Calcyclin-associated annexin) (CAP-50). - Annexin XII from Hydra vulgaris. - Annexin XIII (Intestine-specific annexin) (ISA). - Alpha-Giardins from Giardia intestinalis, primitive homologues of annexins [10,11,12]. The signature pattern for this domain spans positions 9 to 61 of the repeat and includes the only perfectly conserved residue (an arginine in position 22). We also developed a profile which covers the entire annexin repeat. -Consensus pattern: [TG]-[STV]-x(8)-[LIVMF]-x(2)-R-x(3)-[DEQNH]-x(2)-{S}-x(4)- [IFY]-x(7)-[LIVMF]-x(3)-[LIVMF]-x(5)-{I}-x(5)-[LIVMFA]- x(2)-[LIVMF] -Sequences known to belong to this class detected by the pattern: ALL. But the pattern will miss some of the repeats of annexin IX, X, XI, and XII. -Other sequence(s) detected in Swiss-Prot: 8. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: June 2019 / Text revised; profile added. [ 1] Raynal P., Pollard H.B. "Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins." Biochim. Biophys. Acta 1197:63-93(1994). PubMed=8155692 [ 2] Barton G.J., Newman R.H., Freemont P.S., Crumpton M.J. "Amino acid sequence analysis of the annexin super-gene family of proteins." Eur. J. Biochem. 198:749-760(1991). PubMed=1646719 [ 3] Burgoyne R.D., Geisow M.J. "The annexin family of calcium-binding proteins. Review article." Cell Calcium 10:1-10(1989). PubMed=2659190 [ 4] Haigler H.T., Fitch J.M., Jones J.M., Schlaepfer D.D. "Two lipocortin-like proteins, endonexin II and anchorin CII, may be alternate splices of the same gene." Trends Biochem. Sci. 14:48-50(1989). PubMed=2539661 [ 5] Klee C.B. "Ca2+-dependent phospholipid- (and membrane-) binding proteins." Biochemistry 27:6645-6653(1988). PubMed=2973805 [ 6] Smith P.D., Moss S.E. "Structural evolution of the annexin supergene family." Trends Genet. 10:241-246(1994). PubMed=8091504 [ 7] Mirsaeidi M., Gidfar S., Vu A., Schraufnagel D. "Annexins family: insights into their functions and potential role in pathogenesis of sarcoidosis." J. Transl. Med. 14:89-89(2016). PubMed=27071553; DOI=10.1186/s12967-016-0843-7 [ 8] Konopka-Postupolska D., Clark G. "Annexins as Overlooked Regulators of Membrane Trafficking in Plant Cells." Int. J. Mol. Sci. 18:0-0(2017). PubMed=28422051; DOI=10.3390/ijms18040863 [ 9] Huber R., Roemisch J., Paques E.-P. "The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes." EMBO J. 9:3867-3874(1990). PubMed=2147412 [10] Fiedler K., Simons K. "Annexin homologues in Giardia lamblia." Trends Biochem. Sci. 20:177-178(1995). PubMed=7610478 [11] Morgan R.O., Fernandez M.-P. "Molecular phylogeny of annexins and identification of a primitive homologue in Giardia lamblia." Mol. Biol. Evol. 12:967-979(1995). PubMed=8524049; DOI=10.1093/oxfordjournals.molbev.a040290 [12] Weeratunga S.K., Osman A., Hu N.-J., Wang C.K., Mason L., Svaerd S., Hope G., Jones M.K., Hofmann A. "Alpha-1 giardin is an annexin with highly unusual calcium-regulated mechanisms." J. Mol. Biol. 423:169-181(2012). PubMed=22796298; DOI=10.1016/j.jmb.2012.06.041 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}