annexin a6


Summary: Protein of the annexin family with a probable role in exocytotic and endocytotic membrane events.

Top Publications

  1. Grewal T, Enrich C. Molecular mechanisms involved in Ras inactivation: the annexin A6-p120GAP complex. Bioessays. 2006;28:1211-20 pubmed
    ..Recent studies indicate that one member of the annexin family, annexin A6 acts as a targeting protein for p120GAP...
  2. Orito A, Kumanogoh H, Yasaka K, Sokawa J, Hidaka H, Sokawa Y, et al. Calcium-dependent association of annexin VI, protein kinase C alpha, and neurocalcin alpha on the raft fraction derived from the synaptic plasma membrane of rat brain. J Neurosci Res. 2001;64:235-41 pubmed
    ..Further immunoblotting experiments showed the Ca(2+)-dependent association of conventional, but not non-conventional, subtypes of PKC to the raft. ..
  3. Ueng K, Lin C, Yeh H, Wu Y, Liu R, Tsai C, et al. Downregulated cardiac annexin VI mRNA and protein levels in chronically fibrillating human atria. Cardiology. 2008;109:208-16 pubmed
    ..Atrial annexin VI, spatially colocalized with both Na(+)/Ca(2+) exchangers and L-type Ca(2+) channels in the myocyte membrane, is downregulated during chronic AF. ..
  4. Enrich C, Rentero C, de Muga S, Reverter M, Mulay V, Wood P, et al. Annexin A6-Linking Ca(2+) signaling with cholesterol transport. Biochim Biophys Acta. 2011;1813:935-47 pubmed publisher
    b>Annexin A6 (AnxA6) belongs to a conserved family of Ca(2+)-dependent membrane-binding proteins...
  5. Song G, Harding S, Duchen M, Tunwell R, O Gara P, Hawkins T, et al. Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice. FASEB J. 2002;16:622-4 pubmed
    ..In light of published findings showing annexin 6 to be down-regulated in end-stage heart failure, these results are consistent with a role for annexin 6 as a negative inotropic factor in the regulation of cardiomyocyte mechanics. ..
  6. Francia G, Mitchell S, Moss S, Hanby A, Marshall J, Hart I. Identification by differential display of annexin-VI, a gene differentially expressed during melanoma progression. Cancer Res. 1996;56:3855-8 pubmed
    ..Our results provide further evidence for a potential role of Annexin VI in tumor suppression. ..
  7. Barwise J, Walker J. Annexins II, IV, V and VI relocate in response to rises in intracellular calcium in human foreskin fibroblasts. J Cell Sci. 1996;109 ( Pt 1):247-55 pubmed
    ..These results are consistent with an important role for annexins in mediating the calcium signal at the plasma membrane and within the nuclei of fibroblasts. ..
  8. Reverter M, Rentero C, de Muga S, Alvarez Guaita A, Mulay V, Cairns R, et al. Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function. Mol Biol Cell. 2011;22:4108-23 pubmed publisher
    ..We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM...
  9. Schmitz Peiffer C, Browne C, Walker J, Biden T. Activated protein kinase C alpha associates with annexin VI from skeletal muscle. Biochem J. 1998;330 ( Pt 2):675-81 pubmed
    ..Annexin VI is a major skeletal muscle protein and our data are consistent with a role for this isoform in the control of calcium-dependent PKC. ..

More Information


  1. Song G, Campos B, Wagoner L, Dedman J, Walsh R. Altered cardiac annexin mRNA and protein levels in the left ventricle of patients with end-stage heart failure. J Mol Cell Cardiol. 1998;30:443-51 pubmed
    ..Coordinate changes were observed in steady-state mRNA levels. These results suggest that these annexin isoforms may contribute to the regulation of intracellular Ca2+ homeostasis in the cardiomyopathic heart. ..
  2. Koese M, Rentero C, Kota B, Hoque M, Cairns R, Wood P, et al. Annexin A6 is a scaffold for PKC? to promote EGFR inactivation. Oncogene. 2013;32:2858-72 pubmed publisher
    ..Here, we show that ectopic expression of annexin A6 (AnxA6), a member of the Ca(2+) and phospholipid-binding annexins, strongly reduces pY-EGFR levels while ..
  3. Campbell K, Minashima T, Zhang Y, Hadley S, Lee Y, Giovinazzo J, et al. Annexin A6 interacts with p65 and stimulates NF-?B activity and catabolic events in articular chondrocytes. Arthritis Rheum. 2013;65:3120-9 pubmed publisher
    ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic (OA) articular chondrocytes but not in healthy articular chondrocytes. This study was undertaken to determine whether annexin A6 affects catabolic events in these cells...
  4. Chow A, Davis A, Gawler D. Identification of a novel protein complex containing annexin VI, Fyn, Pyk2, and the p120(GAP) C2 domain. FEBS Lett. 2000;469:88-92 pubmed
    ..Finally, co-immunoprecipitation studies in Rat-1 fibroblasts confirm that Fyn, Pyk2, annexin VI and RasGAP can form a protein complex in mammalian cells. ..
  5. Domon M, Matar G, Strzelecka Kiliszek A, Bandorowicz Pikula J, Pikula S, Besson F. Interaction of annexin A6 with cholesterol rich membranes is pH-dependent and mediated by the sterol OH. J Colloid Interface Sci. 2010;346:436-41 pubmed publisher
    b>Annexin A6 (AnxA6), a calcium- and membrane-binding protein, is well-known to play a role in calcium homeostasis, membrane traffic and membrane organization...
  6. Grewal T, Koese M, Rentero C, Enrich C. Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis. Int J Biochem Cell Biol. 2010;42:580-4 pubmed publisher
    b>Annexin A6 (AnxA6) belongs to the highly conserved annexin protein family...
  7. Bode G, Lüken A, Kerkhoff C, Roth J, Ludwig S, Nacken W. Interaction between S100A8/A9 and annexin A6 is involved in the calcium-induced cell surface exposition of S100A8/A9. J Biol Chem. 2008;283:31776-84 pubmed publisher
    ..We identified the phospholipid-binding protein annexin A6 as a potential S100A8/A9 binding protein by affinity chromatography...
  8. Seko Y, Matsumoto A, Fukuda T, Imai Y, Fujimura T, Taka H, et al. A case of neonatal lupus erythematosus presenting delayed dilated cardiomyopathy with circulating autoantibody to annexin A6. Int Heart J. 2007;48:407-15 pubmed
    ..were some autoantibodies against cell surface antigens of cardiac myocytes in the serum from the patient, and annexin A6 was identified as one of the autoantigens...
  9. Buzhynskyy N, Golczak M, Lai Kee Him J, Lambert O, Tessier B, Gounou C, et al. Annexin-A6 presents two modes of association with phospholipid membranes. A combined QCM-D, AFM and cryo-TEM study. J Struct Biol. 2009;168:107-16 pubmed publisher
    ..Possible biological implications of these novel membrane-binding properties of AnxA6 are discussed. ..
  10. Podszywalow Bartnicka P, Kosiorek M, Piwocka K, Sikora E, Zablocki K, Pikula S. Role of annexin A6 isoforms in catecholamine secretion by PC12 cells: distinct influence on calcium response. J Cell Biochem. 2010;111:168-78 pubmed publisher
    ..In this report the effect of annexin A6 (AnxA6) isoforms 1 and 2 on catecholamine secretion has been described...
  11. Monastyrskaya K, Babiychuk E, Hostettler A, Wood P, Grewal T, Draeger A. Plasma membrane-associated annexin A6 reduces Ca2+ entry by stabilizing the cortical actin cytoskeleton. J Biol Chem. 2009;284:17227-42 pubmed publisher
    ..Stable PM localization of membrane-anchored annexin A6 significantly decreased the store-operated Ca(2+) entry (SOCE), but did not influence the rates of Ca(2+) ..
  12. Sztolsztener M, Strzelecka Kiliszek A, Pikula S, Tylki Szymanska A, Bandorowicz Pikula J. Cholesterol as a factor regulating intracellular localization of annexin A6 in Niemann-Pick type C human skin fibroblasts. Arch Biochem Biophys. 2010;493:221-33 pubmed publisher
    ..b>Annexin A6 (AnxA6) is mainly present in cytosol but upon elevation of [Ca(2+)](in) binds to membranes...
  13. Cao X, Genge B, Wu L, Buzzi W, Showman R, Wuthier R. Characterization, cloning and expression of the 67-kDA annexin from chicken growth plate cartilage matrix vesicles. Biochem Biophys Res Commun. 1993;197:556-61 pubmed
    ..coli DH5 alpha in high yield; the physicochemical properties and the amino terminal sequence of the expressed protein exactly matched those of the native protein. ..
  14. Sakwe A, Koumangoye R, Guillory B, Ochieng J. Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions. Exp Cell Res. 2011;317:823-37 pubmed publisher
    The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization ..
  15. Potez S, Luginbühl M, Monastyrskaya K, Hostettler A, Draeger A, Babiychuk E. Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities. J Biol Chem. 2011;286:17982-91 pubmed publisher
    ..Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin ..
  16. Musiol A, Gran S, Ehrhardt C, Ludwig S, Grewal T, Gerke V, et al. Annexin A6-balanced late endosomal cholesterol controls influenza A replication and propagation. MBio. 2013;4:e00608-13 pubmed publisher
    ..We show that shifting of cellular cholesterol pools via the Ca(2+)-regulated membrane-binding protein annexin A6 (AnxA6) affects the infectivity of progeny virus particles...
  17. Golczak M, Kirilenko A, Bandorowicz Pikula J, Desbat B, Pikula S. Structure of human annexin a6 at the air-water interface and in a membrane-bound state. Biophys J. 2004;87:1215-26 pubmed
    We postulate the existence of a pH-sensitive domain in annexin A6 (AnxA6), on the basis of our observation of pH-dependent conformational and orientation changes of this protein and its N- (AnxA6a) and C-terminal (AnxA6b) halves in the ..
  18. de Diego I, Schwartz F, Siegfried H, Dauterstedt P, Heeren J, Beisiegel U, et al. Cholesterol modulates the membrane binding and intracellular distribution of annexin 6. J Biol Chem. 2002;277:32187-94 pubmed
  19. Avila Sakar A, Creutz C, Kretsinger R. Crystal structure of bovine annexin VI in a calcium-bound state. Biochim Biophys Acta. 1998;1387:103-16 pubmed
    ..There are only small differences between the calci- and the apo-annexin VI in the rest of the molecule. Calcium by itself does not promote a major conformational change. ..
  20. Hawkins T, Roes J, Rees D, Monkhouse J, Moss S. Immunological development and cardiovascular function are normal in annexin VI null mutant mice. Mol Cell Biol. 1999;19:8028-32 pubmed
    ..This is the first study of annexin knockout mice, and the lack of a clear phenotype has broad implications for current views of annexin function. ..
  21. Ayala Sanmartin J. Cholesterol enhances phospholipid binding and aggregation of annexins by their core domain. Biochem Biophys Res Commun. 2001;283:72-9 pubmed
    ..These data indicate that the core domain is responsible for the cholesterol-mediated effects. A model for the cholesterol effect in membrane organisation, annexin binding and aggregation is discussed. ..
  22. Minashima T, Small W, Moss S, Kirsch T. Intracellular modulation of signaling pathways by annexin A6 regulates terminal differentiation of chondrocytes. J Biol Chem. 2012;287:14803-15 pubmed publisher
    b>Annexin A6 (AnxA6) is highly expressed in hypertrophic and terminally differentiated growth plate chondrocytes...
  23. Ma H, Kien F, Manière M, Zhang Y, Lagarde N, Tse K, et al. Human annexin A6 interacts with influenza a virus protein M2 and negatively modulates infection. J Virol. 2012;86:1789-801 pubmed publisher
    ..Using yeast two-hybrid screening with M2 CT as bait, a novel interaction with the human annexin A6 (AnxA6) protein was identified, and their physical interaction was confirmed by coimmunoprecipitation assay and ..
  24. Wu C, Taneyhill L. Annexin a6 modulates chick cranial neural crest cell emigration. PLoS ONE. 2012;7:e44903 pubmed publisher
    ..To this end, we have identified Annexin A6 as an important regulator of chick midbrain neural crest cell emigration...
  25. Domon M, Besson F, Bandorowicz Pikula J, Pikula S. Annexin A6 is recruited into lipid rafts of Niemann-Pick type C disease fibroblasts in a Ca2+-dependent manner. Biochem Biophys Res Commun. 2011;405:192-6 pubmed publisher
    ..Some members of the annexin family of proteins such as annexin A2 (AnxA2) and annexin A6 (AnxA6) follow the same route as cholesterol during the endocytic pathway and are found, as AnxA6, attached to ..
  26. Avila Sakar A, Kretsinger R, Creutz C. Membrane-bound 3D structures reveal the intrinsic flexibility of annexin VI. J Struct Biol. 2000;130:54-62 pubmed
    ..It is hypothesized that annexin VI may also adopt several conformations in vivo, underlying different functional roles. ..
  27. Babiychuk E, Draeger A. Annexins in cell membrane dynamics. Ca(2+)-regulated association of lipid microdomains. J Cell Biol. 2000;150:1113-24 pubmed
    ..These interactions bring about a new configuration of membrane-bound constituents, with potentially important consequences for signaling events and Ca(2+) flux. ..
  28. Vilà de Muga S, Timpson P, Cubells L, Evans R, Hayes T, Rentero C, et al. Annexin A6 inhibits Ras signalling in breast cancer cells. Oncogene. 2009;28:363-77 pubmed publisher
    ..Recently, we showed that in EGFR-overexpressing A431 cells, which lack endogenous Annexin A6 (AnxA6), ectopic expression of AnxA6 stimulates membrane recruitment of p120GAP to modulate Ras signalling...
  29. Grewal T, Evans R, Rentero C, Tebar F, Cubells L, de Diego I, et al. Annexin A6 stimulates the membrane recruitment of p120GAP to modulate Ras and Raf-1 activity. Oncogene. 2005;24:5809-20 pubmed
    b>Annexin A6 is a calcium-dependent membrane-binding protein that interacts with signalling proteins, including the GTPase-activating protein p120GAP, one of the most important inactivators of Ras...
  30. Cubells L, Vilà de Muga S, Tebar F, Bonventre J, Balsinde J, Pol A, et al. Annexin A6-induced inhibition of cytoplasmic phospholipase A2 is linked to caveolin-1 export from the Golgi. J Biol Chem. 2008;283:10174-83 pubmed publisher
    ..We recently demonstrated that high expression levels of annexin A6 (AnxA6) perturb the intracellular distribution of cellular cholesterol, thereby inhibiting caveolin export from ..
  31. Smith D, Evans C, Pierce A, Gaskell S, Whetton A. Changes in the proteome associated with the action of Bcr-Abl tyrosine kinase are not related to transcriptional regulation. Mol Cell Proteomics. 2002;1:876-84 pubmed
    ..Leukotriene B4 levels (product of leukotriene A4 hydrolase) were, however, reduced in cells exposed long term to Bcr-Abl activity. This study demonstrates the potential of proteomic analysis to define novel effects of oncogenes. ..
  32. Pons M, Grewal T, Rius E, Schnitgerhans T, Jäckle S, Enrich C. Evidence for the Involvement of annexin 6 in the trafficking between the endocytic compartment and lysosomes. Exp Cell Res. 2001;269:13-22 pubmed
    ..Therefore, we conclude that annexin 6 is involved in the trafficking events leading to LDL degradation. ..
  33. Stogbauer F, Weigert J, Neumeier M, Wanninger J, Sporrer D, Weber M, et al. Annexin A6 is highly abundant in monocytes of obese and type 2 diabetic individuals and is downregulated by adiponectin in vitro. Exp Mol Med. 2009;41:501-7 pubmed publisher
    ..Monocytes express high levels of annexin A6 that could inhibit cholesterol efflux and it was investigated whether the atheroprotective effects of ..
  34. Rentero C, Evans R, Wood P, Tebar F, Vilà de Muga S, Cubells L, et al. Inhibition of H-Ras and MAPK is compensated by PKC-dependent pathways in annexin A6 expressing cells. Cell Signal. 2006;18:1006-16 pubmed
    ..We have recently identified that HDL-induced activation of Ras and Raf-1 is reduced in annexin A6 expressing CHO cells (CHOanx6)...
  35. Cornely R, Rentero C, Enrich C, Grewal T, Gaus K. Annexin A6 is an organizer of membrane microdomains to regulate receptor localization and signalling. IUBMB Life. 2011;63:1009-17 pubmed publisher
    b>Annexin A6 (AnxA6) belongs to the conserved annexin protein family--a group of Ca(2+) -dependent membrane binding proteins...
  36. Grewal T, Heeren J, Mewawala D, Schnitgerhans T, Wendt D, Salomon G, et al. Annexin VI stimulates endocytosis and is involved in the trafficking of low density lipoprotein to the prelysosomal compartment. J Biol Chem. 2000;275:33806-13 pubmed
    ..Thus, data presented in this study suggest that after stimulating endocytosis at the cell surface, annexin VI remains bound to endocytic vesicles to regulate entry of ligands into the prelysosomal compartment. ..
  37. Cubells L, Vilà de Muga S, Tebar F, Wood P, Evans R, Ingelmo Torres M, et al. Annexin A6-induced alterations in cholesterol transport and caveolin export from the Golgi complex. Traffic. 2007;8:1568-89 pubmed
    b>Annexin A6 (AnxA6) belongs to a family of Ca(2+)-dependent membrane-binding proteins and is involved in the regulation of endocytic and exocytic pathways...
  38. Mishra S, Chander V, Banerjee P, Oh J, Lifirsu E, Park W, et al. Interaction of annexin A6 with alpha actinin in cardiomyocytes. BMC Cell Biol. 2011;12:7 pubmed publisher
    ..In myocardial tissue, annexins A2, A5 and A6 are particularly abundant, of which the expression levels of annexin A6 has been found to be maximal...
  39. Locate S, Colyer J, Gawler D, Walker J. Annexin A6 at the cardiac myocyte sarcolemma--evidence for self-association and binding to actin. Cell Biol Int. 2008;32:1388-96 pubmed publisher
    ..b>Annexin A6 is a major cellular calcium and phospholipid binding protein...
  40. Massey Harroche D, Mayran N, Maroux S. Polarized localizations of annexins I, II, VI and XIII in epithelial cells of intestinal, hepatic and pancreatic tissues. J Cell Sci. 1998;111 ( Pt 20):3007-15 pubmed
    ..In conclusion, this study shows that the basolateral domain of polarized cells appears to be the main site where annexins are located, and they may therefore be involved in the important cellular events occurring at this level. ..
  41. Swaggart K, Demonbreun A, Vo A, Swanson K, Kim E, Fahrenbach J, et al. Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair. Proc Natl Acad Sci U S A. 2014;111:6004-9 pubmed publisher
    ..Whole genome and RNA sequencing identified Anxa6, encoding annexin A6, as a modifier gene...
  42. Strzelecka Kiliszek A, Buszewska M, Podszywalow Bartnicka P, Pikula S, Otulak K, Buchet R, et al. Calcium- and pH-dependent localization of annexin A6 isoforms in Balb/3T3 fibroblasts reflecting their potential participation in vesicular transport. J Cell Biochem. 2008;104:418-34 pubmed
    b>Annexin A6 (AnxA6), calcium- and membrane-binding protein, is involved in membrane dynamics. It exists in the cell in two isoforms, AnxA6-1 and AnxA6-2, varying only by the VAAEIL sequence. In most cells, AnxA6-1 predominates...
  43. Theobald J, Hanby A, Patel K, Moss S. Annexin VI has tumour-suppressor activity in human A431 squamous epithelial carcinoma cells. Br J Cancer. 1995;71:786-8 pubmed
    ..The tumours formed by the annexin VI+ A431 cells were morphologically and histologically similar to those formed by the wild-type cells. ..
  44. Jaruga E, Salvioli S, Dobrucki J, Chrul S, Bandorowicz Pikuła J, Sikora E, et al. Apoptosis-like, reversible changes in plasma membrane asymmetry and permeability, and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes. FEBS Lett. 1998;433:287-93 pubmed
  45. Brownawell A, Creutz C. Calcium-dependent binding of the plasma protein apolipoprotein A-I to two members of the annexin family. Biochemistry. 1996;35:6839-45 pubmed
    ..Other annexins, such as annexin IV and annexin VI, do not exhibit this binding. The results suggest that certain annexins may function as extracellular binding sites for plasma proteins. ..
  46. Chlystun M, Campanella M, Law A, Duchen M, Fatimathas L, Levine T, et al. Regulation of mitochondrial morphogenesis by annexin A6. PLoS ONE. 2013;8:e53774 pubmed publisher
    ..Our results suggest that anxA6 inhibits Drp1 activity, and that Ca(2+)-binding to anxA6 relieves this inhibition to permit Drp1-mediated mitochondrial fission. ..
  47. Riquelme G, Llanos P, Tischner E, Neil J, Campos B. Annexin 6 modulates the maxi-chloride channel of the apical membrane of syncytiotrophoblast isolated from human placenta. J Biol Chem. 2004;279:50601-8 pubmed
    ..Together these data suggest that annexin 6 could play an important role in ion transport of the placenta. ..
  48. Fitzpatrick S, Waisman D. The uptake of calcium by isolated chromaffin granules of the adrenal medulla. Mol Cell Biochem. 1996;155:121-30 pubmed
    ..These results suggest that Ca2+ uptake in adrenal chromaffin granules is regulated by Na+ and Ca2+ gradients and also possibly by annexins V and VI. ..
  49. Bandorowicz Pikuła J, Awasthi Y. Interaction of annexins IV and VI with ATP. An alternative mechanism by which a cellular function of these calcium- and membrane-binding proteins is regulated. FEBS Lett. 1997;409:300-6 pubmed
    ..Any significant 8-azido-ATP or TNP-ATP binding was not observed with AnxIV. ATP modulated the binding of AnxVI to erythrocyte membrane and increased the Ca2+ concentration required for half-maximal binding of AnxVI to F-actin. ..
  50. Belluoccio D, Grskovic I, Niehoff A, Schlötzer Schrehardt U, Rosenbaum S, Etich J, et al. Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization. J Bone Miner Res. 2010;25:141-53 pubmed publisher
    ..These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo. ..
  51. Bian Z, Tang Q, Wu H, Huang J, Shen D. Change of cardiac function in experimental autoimmune myocarditis is correlated with the expression of annexin VI. Acta Cardiol. 2009;64:71-7 pubmed
    ..Annexin VI is down-regulated in the acute phase of EAM, and overexpressed in the chronic phase of EAM. Annexin-VI may be responsible for the compensation and aggravation of cardiac function in different phases of EAM. ..
  52. Pfander D, Swoboda B, Kirsch T. Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes. Am J Pathol. 2001;159:1777-83 pubmed
    ..These results suggest that the expression of early (proliferating cell nuclear antigen, syndecan-3) and late differentiation markers (annexin VI, alkaline phosphatase) is activated in chondrocytes of osteoarthritic cartilage. ..
  53. Kirsch T, Harrison G, Golub E, Nah H. The roles of annexins and types II and X collagen in matrix vesicle-mediated mineralization of growth plate cartilage. J Biol Chem. 2000;275:35577-83 pubmed