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Physiol. Rev. 82: 331-371, 2002;
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Physiological Reviews, Vol. 82, No. 2, April 2002, pp. 331-371; 10.1152/physrev.00030.2001.
Copyright ©2002 by the American Physiological Society

Annexins: From Structure to Function

Volker Gerke and Stephen E. Moss

Institute for Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, Münster, Germany; and Department of Cell Biology, Institute of Ophthalmology, University College London, London, United Kingdom

Gerke, Volker and Stephen E. Moss. Annexins: From Structure to Function. Physiol. Rev. 82: 331-371, 2002.Annexins are Ca2+ and phospholipid binding proteins forming an evolutionary conserved multigene family with members of the family being expressed throughout animal and plant kingdoms. Structurally, annexins are characterized by a highly alpha -helical and tightly packed protein core domain considered to represent a Ca2+-regulated membrane binding module. Many of the annexin cores have been crystallized, and their molecular structures reveal interesting features that include the architecture of the annexin-type Ca2+ binding sites and a central hydrophilic pore proposed to function as a Ca2+ channel. In addition to the conserved core, all annexins contain a second principal domain. This domain, which NH2-terminally precedes the core, is unique for a given member of the family and most likely specifies individual annexin properties in vivo. Cellular and animal knock-out models as well as dominant-negative mutants have recently been established for a number of annexins, and the effects of such manipulations are strikingly different for different members of the family. At least for some annexins, it appears that they participate in the regulation of membrane organization and membrane traffic and the regulation of ion (Ca2+) currents across membranes or Ca2+ concentrations within cells. Although annexins lack signal sequences for secretion, some members of the family have also been identified extracellularly where they can act as receptors for serum proteases on the endothelium as well as inhibitors of neutrophil migration and blood coagulation. Finally, deregulations in annexin expression and activity have been correlated with human diseases, e.g., in acute promyelocytic leukemia and the antiphospholipid antibody syndrome, and the term annexinopathies has been coined.




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Y. E. Kim, J. M. Isas, H. T. Haigler, and R. Langen
A Helical Hairpin Region of Soluble Annexin B12 Refolds and Forms a Continuous Transmembrane Helix at Mildly Acidic pH
J. Biol. Chem., September 16, 2005; 280(37): 32398 - 32404.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S.-i. Kubo, V. M. Nemani, R. J. Chalkley, M. D. Anthony, N. Hattori, Y. Mizuno, R. H. Edwards, and D. L. Fortin
A Combinatorial Code for the Interaction of {alpha}-Synuclein with Membranes
J. Biol. Chem., September 9, 2005; 280(36): 31664 - 31672.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
J. Karlsson, H. Fu, F. Boulay, C. Dahlgren, K. Hellstrand, and C. Movitz
Neutrophil NADPH-oxidase activation by an annexin AI peptide is transduced by the formyl peptide receptor (FPR), whereas an inhibitory signal is generated independently of the FPR family receptors
J. Leukoc. Biol., September 1, 2005; 78(3): 762 - 771.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
J. Wu, M. Kobayashi, E. A. Sousa, W. Liu, J. Cai, S. J. Goldman, A. J. Dorner, S. J. Projan, M. S. Kavuru, Y. Qiu, et al.
Differential Proteomic Analysis of Bronchoalveolar Lavage Fluid in Asthmatics following Segmental Antigen Challenge
Mol. Cell. Proteomics, September 1, 2005; 4(9): 1251 - 1264.
[Abstract] [Full Text] [PDF]

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 Exp PhysiolHome page
T. De Celle, F. Vanrobaeys, P. Lijnen, W. M. Blankesteijn, S. Heeneman, J. Van Beeumen, B. Devreese, J. F. M Smits, and B. J. A Janssen
Alterations in mouse cardiac proteome after in vivo myocardial infarction: permanent ischaemia versus ischaemia-reperfusion
Exp Physiol, July 1, 2005; 90(4): 593 - 606.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Kwon, C.-S. Yoon, W. Jeong, S. G. Rhee, and D. M. Waisman
Annexin A2-S100A10 Heterotetramer, a Novel Substrate of Thioredoxin
J. Biol. Chem., June 24, 2005; 280(25): 23584 - 23592.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
A. Cabezas, K. G. Bache, A. Brech, and H. Stenmark
Alix regulates cortical actin and the spatial distribution of endosomes
J. Cell Sci., June 15, 2005; 118(12): 2625 - 2635.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
B. A. Babbin and A. T. Gewirtz
A Most Important Annexation
Am. J. Pathol., June 1, 2005; 166(6): 1581 - 1583.
[Full Text] [PDF]

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 Am. J. Pathol.Home page
A. S. Damazo, S. Yona, F. D'Acquisto, R. J. Flower, S. M. Oliani, and M. Perretti
Critical Protective Role for Annexin 1 Gene Expression in the Endotoxemic Murine Microcirculation
Am. J. Pathol., June 1, 2005; 166(6): 1607 - 1617.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Semov, M. J. Moreno, A. Onichtchenko, A. Abulrob, M. Ball, I. Ekiel, G. Pietrzynski, D. Stanimirovic, and V. Alakhov
Metastasis-associated Protein S100A4 Induces Angiogenesis through Interaction with Annexin II and Accelerated Plasmin Formation
J. Biol. Chem., May 27, 2005; 280(21): 20833 - 20841.
[Abstract] [Full Text] [PDF]

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 BloodHome page
H.-H. Chen, C. P. Vicente, L. He, D. M. Tollefsen, and T.-C. Wun
Fusion proteins comprising annexin V and Kunitz protease inhibitors are highly potent thrombogenic site-directed anticoagulants
Blood, May 15, 2005; 105(10): 3902 - 3909.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
G. Jeschke, A. Bender, T. Schweikardt, G. Panek, H. Decker, and H. Paulsen
Localization of the N-terminal Domain in Light-harvesting Chlorophyll a/b Protein by EPR Measurements
J. Biol. Chem., May 13, 2005; 280(19): 18623 - 18630.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
E. Camors, V. Monceau, and D. Charlemagne
Annexins and Ca2+ handling in the heart
Cardiovasc Res, March 1, 2005; 65(4): 793 - 802.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
S. Chasserot-Golaz, N. Vitale, E. Umbrecht-Jenck, D. Knight, V. Gerke, and M.-F. Bader
Annexin 2 Promotes the Formation of Lipid Microdomains Required for Calcium-regulated Exocytosis of Dense-Core Vesicles
Mol. Biol. Cell, March 1, 2005; 16(3): 1108 - 1119.
[Abstract] [Full Text] [PDF]

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 BloodHome page
J. Zhang and K. R. McCrae
Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-{beta}2 glycoprotein I antibodies
Blood, March 1, 2005; 105(5): 1964 - 1969.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Yamada, K. Irie, T. Hirota, T. Ooshio, A. Fukuhara, and Y. Takai
Involvement of the Annexin II-S100A10 Complex in the Formation of E-cadherin-based Adherens Junctions in Madin-Darby Canine Kidney Cells
J. Biol. Chem., February 18, 2005; 280(7): 6016 - 6027.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Lu, K. I. Izvolsky, J. Qian, and W. V. Cardoso
Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis
J. Biol. Chem., February 11, 2005; 280(6): 4834 - 4841.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
J. G. J. Hoenderop, B. Nilius, and R. J. M. Bindels
Calcium Absorption Across Epithelia
Physiol Rev, January 1, 2005; 85(1): 373 - 422.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
A. Cederholm, E. Svenungsson, K. Jensen-Urstad, C. Trollmo, A.-K. Ulfgren, J. Swedenborg, G.-Z. Fei, and J. Frostegard
Decreased Binding of Annexin V to Endothelial Cells: A Potential Mechanism in Atherothrombosis of Patients With Systemic Lupus Erythematosus
Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 198 - 203.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
H. Kenis, H. van Genderen, A. Bennaghmouch, H. A. Rinia, P. Frederik, J. Narula, L. Hofstra, and C. P. M. Reutelingsperger
Cell Surface-expressed Phosphatidylserine and Annexin A5 Open a Novel Portal of Cell Entry
J. Biol. Chem., December 10, 2004; 279(50): 52623 - 52629.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. V. Dorovkov and A. G. Ryazanov
Phosphorylation of Annexin I by TRPM7 Channel-Kinase
J. Biol. Chem., December 3, 2004; 279(49): 50643 - 50646.
[Abstract] [Full Text] [PDF]

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 JNMHome page
T. Takei, Y. Kuge, S. Zhao, M. Sato, H. W. Strauss, F. G. Blankenberg, J. F. Tait, and N. Tamaki
Time Course of Apoptotic Tumor Response After a Single Dose of Chemotherapy: Comparison with 99mTc-Annexin V Uptake and Histologic Findings in an Experimental Model
J. Nucl. Med., December 1, 2004; 45(12): 2083 - 2087.
[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
A. P. Ponnampalam, G. C. Weston, A. C. Trajstman, B. Susil, and P. A.W. Rogers
Molecular classification of human endometrial cycle stages by transcriptional profiling
Mol. Hum. Reprod., December 1, 2004; 10(12): 879 - 893.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
V. Monceau, Y. Belikova, G. Kratassiouk, D. Charue, E. Camors, C. Communal, P. Trouve, F. Russo-Marie, and D. Charlemagne
Externalization of endogenous annexin A5 participates in apoptosis of rat cardiomyocytes
Cardiovasc Res, December 1, 2004; 64(3): 496 - 506.
[Abstract] [Full Text] [PDF]

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 JEMHome page
G. Ma, T. Greenwell-Wild, K. Lei, W. Jin, J. Swisher, N. Hardegen, C. T. Wild, and S. M. Wahl
Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection
J. Exp. Med., November 15, 2004; 200(10): 1337 - 1346.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. M. Hinsby, J. V. Olsen, and M. Mann
Tyrosine Phosphoproteomics of Fibroblast Growth Factor Signaling: A ROLE FOR INSULIN RECEPTOR SUBSTRATE-4
J. Biol. Chem., November 5, 2004; 279(45): 46438 - 46447.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
W. Xiang, O. Windl, G. Wunsch, M. Dugas, A. Kohlmann, N. Dierkes, I. M. Westner, and H. A. Kretzschmar
Identification of Differentially Expressed Genes in Scrapie-Infected Mouse Brains by Using Global Gene Expression Technology
J. Virol., October 15, 2004; 78(20): 11051 - 11060.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. B. Deora, G. Kreitzer, A. T. Jacovina, and K. A. Hajjar
An Annexin 2 Phosphorylation Switch Mediates p11-dependent Translocation of Annexin 2 to the Cell Surface
J. Biol. Chem., October 15, 2004; 279(42): 43411 - 43418.
[Abstract] [Full Text] [PDF]

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 Plant Cell PhysiolHome page
T. Okamoto, K. Higuchi, T. Shinkawa, T. Isobe, H. Lorz, T. Koshiba, and E. Kranz
Identification of Major Proteins in Maize Egg Cells
Plant Cell Physiol., October 15, 2004; 45(10): 1406 - 1412.
[Abstract] [Full Text] [PDF]

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 Mol Biol EvolHome page
T. Nagata, S. Iizumi, K. Satoh, H. Ooka, J. Kawai, P. Carninci, Y. Hayashizaki, Y. Otomo, K. Murakami, K. Matsubara, et al.
Comparative Analysis of Plant and Animal Calcium Signal Transduction Element Using Plant Full-Length cDNA Data
Mol. Biol. Evol., October 1, 2004; 21(10): 1855 - 1870.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Jin, C. Smith, H.-Y. Hsieh, D. F. Gibson, and J. F. Tait
Essential Role of B-helix Calcium Binding Sites in Annexin V-Membrane Binding
J. Biol. Chem., September 24, 2004; 279(39): 40351 - 40357.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T.-Y. Ling, C.-L. Chen, Y.-H. Huang, I-H. Liu, S. S. Huang, and J. S. Huang
Identification and Characterization of the Acidic pH Binding Sites for Growth Regulatory Ligands of Low Density Lipoprotein Receptor-related Protein-1
J. Biol. Chem., September 10, 2004; 279(37): 38736 - 38748.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
D. B. N. Lee, N. Jamgotchian, S. G. Allen, F. W. K. Kan, and I. L. Hale
Annexin A2 heterotetramer: role in tight junction assembly
Am J Physiol Renal Physiol, September 1, 2004; 287(3): F481 - F491.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
P. Turowski, P. Adamson, J. Sathia, J. J. Zhang, S. E. Moss, G. W. Aylward, M. J. Hayes, N. Kanuga, and J. Greenwood
Basement Membrane-Dependent Modification of Phenotype and Gene Expression in Human Retinal Pigment Epithelial ARPE-19 Cells
Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2786 - 2794.
[Abstract] [Full Text] [PDF]


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