annexin a4


Summary: Protein of the annexin family originally isolated from the electric organ of the electric ray Torpedo marmorata. It has been found in a wide range of mammalian tissue where it is localized to the apical membrane of polarized EPITHELIAL CELLS.

Top Publications

  1. Han E, Tahir S, Cherian S, Collins N, Ng S. Modulation of paclitaxel resistance by annexin IV in human cancer cell lines. Br J Cancer. 2000;83:83-8 pubmed
    ..Thus our results indicate that annexin IV plays a role in paclitaxel resistance in this cell line and it is among one of the earliest proteins that is induced in cells in response to cytotoxic stress such as antimitotic drug treatment. ..
  2. Li B, Dedman J, Kaetzel M. Intron disruption of the annexin IV gene reveals novel transcripts. J Biol Chem. 2003;278:43276-83 pubmed
    ..The AIVa-/- mouse may become a valuable model to further study transcription and the physiological role of annexin IV. ..
  3. Toyama A, Suzuki A, Shimada T, Aoki C, Aoki Y, Umino Y, et al. Proteomic characterization of ovarian cancers identifying annexin-A4, phosphoserine aminotransferase, cellular retinoic acid-binding protein 2, and serpin B5 as histology-specific biomarkers. Cancer Sci. 2012;103:747-55 pubmed publisher
  4. Yamashita T, Nagano K, Kanasaki S, Maeda Y, Furuya T, Inoue M, et al. Annexin A4 is a possible biomarker for cisplatin susceptibility of malignant mesothelioma cells. Biochem Biophys Res Commun. 2012;421:140-4 pubmed publisher
    ..distinguish between mesothelioma cells of different CDDP susceptibilities, and this revealed that expression of annexin A4 (ANXA4) protein was higher in CDDP-resistant cells than in CDDP-susceptible cells...
  5. Lin L, Huang H, Juan H. Revealing the molecular mechanism of gastric cancer marker annexin A4 in cancer cell proliferation using exon arrays. PLoS ONE. 2012;7:e44615 pubmed publisher
    ..A potential biomarker for gastric cancer is the protein annexin A4 (ANXA4), an intracellular Ca(2+) sensor...
  6. Mayran N, Traverso V, Maroux S, Massey Harroche D. Cellular and subcellular localizations of annexins I, IV, and VI in lung epithelia. Am J Physiol. 1996;270:L863-71 pubmed
    ..Annexin VI was expressed only by alveolar endothelial cells, where it was probably cytoplasmic. None of these three annexins seem to be expressed in the nondifferentiated tracheal basal epithelial cells...
  7. Hill W, Kaetzel M, Kishore B, Dedman J, Zeidel M. Annexin A4 reduces water and proton permeability of model membranes but does not alter aquaporin 2-mediated water transport in isolated endosomes. J Gen Physiol. 2003;121:413-25 pubmed
    b>Annexin A4 (Anx4) belongs to a ubiquitous family of Ca2+-dependent membrane-binding proteins thought to be involved in membrane trafficking and membrane organization within cells...
  8. Zimmermann U, Balabanov S, Giebel J, Teller S, Junker H, Schmoll D, et al. Increased expression and altered location of annexin IV in renal clear cell carcinoma: a possible role in tumour dissemination. Cancer Lett. 2004;209:111-8 pubmed
    ..From these results above it seems possible that annexin IV plays an important role in the morphological diversification and dissemination of the clear cell renal cell carcinoma. ..
  9. Ohkawa H, Sohma H, Sakai R, Kuroki Y, Hashimoto E, Murakami S, et al. Ethanol-induced augmentation of annexin IV in cultured cells and the enhancement of cytotoxicity by overexpression of annexin IV by ethanol. Biochim Biophys Acta. 2002;1588:217-25 pubmed
    ..Thus, it might be indicated that the amount of annexin IV is selectively augmented and this augmentation facilitates the development of cell lesion by ethanol. ..

More Information


  1. Masuda J, Takayama E, Satoh A, Ida M, Shinohara T, Kojima Aikawa K, et al. Levels of annexin IV and V in the plasma of pregnant and postpartum women. Thromb Haemost. 2004;91:1129-36 pubmed
  2. Miao Y, Cai B, Liu L, Yang Y, Wan X. Annexin IV is differentially expressed in clear cell carcinoma of the ovary. Int J Gynecol Cancer. 2009;19:1545-9 pubmed publisher
    ..The overexpression of Annexin IV may be an ovarian CCC-specific molecular marker. ..
  3. Seville R, Nijjar S, Barnett M, Masse K, Jones E. Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules. Development. 2002;129:1693-704 pubmed
    ..In this study, we demonstrate an in vivo role for annexin IV in the development of the pronephric tubules in Xenopus laevis. ..
  4. Choi C, Sung C, Kim H, Lee Y, Song S, Song T, et al. Overexpression of annexin A4 is associated with chemoresistance in papillary serous adenocarcinoma of the ovary. Hum Pathol. 2013;44:1017-23 pubmed publisher
    b>Annexin A4 study in ovarian cancer has been primarily focused on clear cell carcinoma, which exhibits strong resistance to chemotherapy...
  5. Gaudio E, Paduano F, Spizzo R, Ngankeu A, Zanesi N, Gaspari M, et al. Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel. PLoS ONE. 2013;8:e78610 pubmed publisher
    ..Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel...
  6. Piljic A, Schultz C. Annexin A4 self-association modulates general membrane protein mobility in living cells. Mol Biol Cell. 2006;17:3318-28 pubmed
    Annexins are Ca2+-regulated phospholipid-binding proteins whose function is only partially understood. Annexin A4 is a member of this family that is believed to be involved in exocytosis and regulation of epithelial Cl- secretion...
  7. Zschornig O, Opitz F, Muller M. Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium. Eur Biophys J. 2007;36:415-24 pubmed
    b>Annexin A4 belongs to a class of Ca(2+)-binding proteins for which different functions in the cell have proposed, e.g. involvement in exocytosis and in the coagulation process...
  8. Kim A, Enomoto T, Serada S, Ueda Y, Takahashi T, Ripley B, et al. Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin. Int J Cancer. 2009;125:2316-22 pubmed publisher
    ..Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass ..
  9. Zanotti G, Malpeli G, Gliubich F, Folli C, Stoppini M, Olivi L, et al. Structure of the trigonal crystal form of bovine annexin IV. Biochem J. 1998;329 ( Pt 1):101-6 pubmed
    ..The propensity of several annexins to generate similar trimeric arrays supports the hypothesis that trimeric complexes of such annexins, including annexin IV, may represent the functional units that interact with membranes. ..
  10. Crosby K, Postma M, Hink M, Zeelenberg C, Adjobo Hermans M, Gadella T. Quantitative analysis of self-association and mobility of annexin A4 at the plasma membrane. Biophys J. 2013;104:1875-85 pubmed publisher
    ..b>Annexin A4 (AnxA4) has been implicated in diverse cellular processes, including the regulation of exocytosis and ion-..
  11. Kaetzel M, Mo Y, Mealy T, Campos B, Bergsma Schutter W, Brisson A, et al. Phosphorylation mutants elucidate the mechanism of annexin IV-mediated membrane aggregation. Biochemistry. 2001;40:4192-9 pubmed
    ..The data suggest that reversible complex formation through phosphorylation and dephosphorylation could occur in vivo and play a role in the regulation of vesicle trafficking following changes in physiological states. ..
  12. Liu L, Wang S, Zhang Q, Ding Y. Identification of potential genes/proteins regulated by Tiam1 in colorectal cancer by microarray analysis and proteome analysis. Cell Biol Int. 2008;32:1215-22 pubmed publisher
    ..Analysis of these proteins, which may be directly or indirectly regulated by Tiam1, may provide insight into the role and mechanism of Tiam1 in colorectal cancer metastasis. ..
  13. Jeon Y, Kim D, Jung H, Chung S, Chi S, Cho S, et al. Annexin A4 interacts with the NF-kappaB p50 subunit and modulates NF-kappaB transcriptional activity in a Ca2+-dependent manner. Cell Mol Life Sci. 2010;67:2271-81 pubmed publisher
    Previously, we identified annexin A4 (ANXA4) as a candidate substrate of caspase-3. Proteomic studies were performed to identify interacting proteins with a view to determining the roles of ANXA4. ANXA4 was found to interact with the p105...
  14. Kim A, Serada S, Enomoto T, Naka T. Targeting annexin A4 to counteract chemoresistance in clear cell carcinoma of the ovary. Expert Opin Ther Targets. 2010;14:963-71 pubmed publisher
    ..of ovarian CCC; the role of annexin family proteins in tumor development and progression; the role of annexin A4 in enhancing cellular drug resistance; recent studies linking annexin A4 overexpression to chemoresistance in ..
  15. Dreier R, Schmid K, Gerke V, Riehemann K. Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study. Histochem Cell Biol. 1998;110:137-48 pubmed
    ..The characteristic expression in different tissues and the intracellular distribution indicates that the three annexins investigated are involved in aspects of differentiation and/or physiological functions specific to these tissues. ..
  16. Almeida P, Sohma H, Rasch K, Wieser C, Hinderliter A. Allosterism in membrane binding: a common motif of the annexins?. Biochemistry. 2005;44:10905-13 pubmed
  17. De la Cuesta F, Alvarez Llamas G, Maroto A, Donado A, Zubiri I, Posada M, et al. A proteomic focus on the alterations occurring at the human atherosclerotic coronary intima. Mol Cell Proteomics. 2011;10:M110.003517 pubmed publisher
    ..For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. ..
  18. Shi T, Dong F, Liou L, Duan Z, Novick A, DiDonato J. Differential protein profiling in renal-cell carcinoma. Mol Carcinog. 2004;40:47-61 pubmed
  19. Kojima K, Yamamoto K, Irimura T, Osawa T, Ogawa H, Matsumoto I. Characterization of carbohydrate-binding protein p33/41: relation with annexin IV, molecular basis of the doublet forms (p33 and p41), and modulation of the carbohydrate binding activity by phospholipids. J Biol Chem. 1996;271:7679-85 pubmed
    ..These results suggest that p33/41 binds two types of ligands via different sites and that phospholipids modulate the carbohydrate binding activity of p33/41. ..
  20. Sohma H, Creutz C, Gasa S, Ohkawa H, Akino T, Kuroki Y. Differential lipid specificities of the repeated domains of annexin IV. Biochim Biophys Acta. 2001;1546:205-15 pubmed
  21. Sohma H, Ohkawa H, Hashimoto E, Toki S, Ozawa H, Kuroki Y, et al. Alteration of annexin IV expression in alcoholics. Alcohol Clin Exp Res. 2001;25:55S-8S pubmed
    ..It was shown further that autoantibodies to annexin IV were increased significantly in alcoholic patients compared with controls. Thus, annexin IV may become a novel biological marker for alcoholics. ..
  22. Blackwood R, Ernst J. Characterization of Ca2(+)-dependent phospholipid binding, vesicle aggregation and membrane fusion by annexins. Biochem J. 1990;266:195-200 pubmed
    ..Whereas previous reports have emphasized properties that the annexins have in common, these findings reveal quantitative and qualitative differences among the annexins which may relate to distinct intracellular functions. ..
  23. Kaplan R, Jaye M, Burgess W, Schlaepfer D, Haigler H. Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein. J Biol Chem. 1988;263:8037-43 pubmed
  24. Chen J, Chou Y, Chen K, Hung R, Yu J, Chang Y, et al. Detection of annexin A autoantibodies in sera from colorectal cancer patients. J Clin Gastroenterol. 2011;45:125-32 pubmed publisher
    ..3% seropositivity) at the early stage of CRC. Measurement of ANXA autoantibody levels may provide an alternative detection indicator for CRC, particularly among early-stage patients. ..
  25. Sable C, Riches D. Cloning and functional activity of a novel truncated form of annexin IV in mouse macrophages. Biochem Biophys Res Commun. 1999;258:162-7 pubmed
    ..The existence of a novel form of annexin IV in mouse macrophages may aid in further defining the role of members of the annexin family. ..
  26. Sohma H, Creutz C, Saitoh M, Sano H, Kuroki Y, Voelker D, et al. Characterization of the Ca2+-dependent binding of annexin IV to surfactant protein A. Biochem J. 1999;341 ( Pt 1):203-9 pubmed
    ..These results suggest that the Ca2+ binding to domain 3 of annexin IV is required for the Ca2+-dependent binding by SP-A and that Arg197 of SP-A is important in this binding. ..
  27. Butsushita K, Fukuoka S, Ida K, Arii Y. Crystal structures of sodium-bound annexin A4. Biosci Biotechnol Biochem. 2009;73:2274-80 pubmed
    b>Annexin A4 (Anx4) possesses four repeat domains with one Ca(2+)-binding site (CBS) in each domain. In this study, we resolved two crystal structures of the Na(+)-bound form at high resolution (1.58 and 1.35 A)...
  28. Wu L, Wei X, Ling J, Liu L, Liu S, Li M, et al. Early osteogenic differential protein profile detected by proteomic analysis in human periodontal ligament cells. J Periodontal Res. 2009;44:645-56 pubmed publisher
  29. Kulik L, Fleming S, Moratz C, Reuter J, Novikov A, Chen K, et al. Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury. J Immunol. 2009;182:5363-73 pubmed publisher
    ..These data in toto identify annexin IV as a key ischemia-related target Ag that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. ..
  30. Laufer E, Reutelingsperger C, Narula J, Hofstra L. Annexin A5: an imaging biomarker of cardiovascular risk. Basic Res Cardiol. 2008;103:95-104 pubmed publisher
    ..In this review we will discuss the introduction of Annexin A5 in preclinical and clinical imaging studies and provide an outlook on novel opportunities of Annexin A5 based targeting of PS. ..
  31. Ponnampalam A, Rogers P. Cyclic changes and hormonal regulation of annexin IV mRNA and protein in human endometrium. Mol Hum Reprod. 2006;12:661-9 pubmed
    ..This is the first study to show that ANXA4 transcription and translation are regulated by progesterone and suggests that ANXA4 may be important in regulating ion and water transport across the endometrial epithelium. ..
  32. Kita E, Katsui N, Emoto M, Sawaki M, Oku D, Nishikawa F, et al. Virulence of transparent and opaque colony types of Neisseria gonorrhoeae for the genital tract of mice. J Med Microbiol. 1991;34:355-62 pubmed
    ..Furthermore, gonococcal survival in the female genital tract might be attributable to phase variation from Tr to Op phenotypes. ..
  33. Zhang F, Sha J, Wood T, Galindo C, Garner H, Burkart M, et al. Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA). Cell Signal. 2008;20:844-61 pubmed publisher
    ..assays revealed increased production of proinflammatory cytokine IL-32 and a decrease in the production of annexin A4 and clusterin compared to plaa(low) cells...
  34. Fukuoka S, Kern H, Kazuki Sugino R, Ikeda Y. Cloning and characterization of ZAP36, an annexin-like, zymogen granule membrane associated protein, in exocrine pancreas. Biochim Biophys Acta. 2002;1575:148-52 pubmed
    ..ZAP36 is found to be a novel member of annexin IV, and showed an apical localization in exocrine pancreas and an ubiquitous expression in epithelial tissues. ZAP36 may be involved in exocytosis in apical regions of polarized cells. ..
  35. Skrahina T, Piljic A, Schultz C. Heterogeneity and timing of translocation and membrane-mediated assembly of different annexins. Exp Cell Res. 2008;314:1039-47 pubmed publisher
    ..The formation of homo- and heterogeneous annexin assemblies may play an important role when high increases in calcium occur, such as after disruption of the plasma membrane. ..
  36. Tsujii Hayashi Y, Kitahara M, Yamagaki T, Kojima Aikawa K, Matsumoto I. A potential endogenous ligand of annexin IV in the exocrine pancreas. Carbohydrate structure of GP-2, a glycosylphosphatidylinositol-anchored glycoprotein of zymogen granule membranes. J Biol Chem. 2002;277:47493-9 pubmed
    ..GP-2 was found to localize exclusively in the same apical cytoplasmic region of pancreatic acinar cells as annexin IV does. These results suggest that GP-2 is an endogenous ligand of annexin IV in the exocrine pancreas. ..
  37. Li J, Tan Z, Li M, Liu Y, Liu Q, Gu X, et al. [Study of altered expression of annexin IV and human endometrial receptivity]. Zhonghua Fu Chan Ke Za Zhi. 2006;41:803-5 pubmed
    ..It seems possible that the increased expression of annexin IV during the implantation window plays an important role in the morphological differentiation of the uterus to the receptive state. ..
  38. Masuda J, Takayama E, Satoh A, Kojima Aikawa K, Suzuki K, Matsumoto I. A novel expression vector, designated as pHisJM, for producing recombinant His-fusion proteins. Biotechnol Lett. 2004;26:1543-8 pubmed
  39. Satoh A, Takayama E, Kojima K, Ogawa H, Yamori T, Sato S, et al. Expression of carbohydrate-binding protein p33/41 in human tumor cell lines. J Biochem. 1996;119:346-53 pubmed
    ..However, one of the cell surface proteins first labeled with biotin and then solubilized with a detergent was immunoprecipitated with AS17. The results suggest the existence of a membrane spanning form of p33/41 (annexin IV). ..
  40. Han C, Chen J, Chan E, Wu C, Yu K, Chen K, et al. An informatics-assisted label-free approach for personalized tissue membrane proteomics: case study on colorectal cancer. Mol Cell Proteomics. 2011;10:M110.003087 pubmed publisher
    ..Further validation of a panel of proteins, annexin A4, neutrophils defensin A1, and claudin 3, confirmed differential expression levels and high occurrences (48-70%) ..
  41. Staquicini F, Cardo Vila M, Kolonin M, Trepel M, Edwards J, Nunes D, et al. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proc Natl Acad Sci U S A. 2011;108:18637-42 pubmed publisher
    ..Two are shared among multiple tissues (integrin ?4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal ..
  42. Hill W, Meyers S, von Bodungen M, Apodaca G, Dedman J, Kaetzel M, et al. Studies on localization and function of annexin A4a within urinary bladder epithelium using a mouse knockout model. Am J Physiol Renal Physiol. 2008;294:F919-27 pubmed publisher
    b>Annexin A4 (anxA4) is a member of the Ca(2+)-dependent membrane-binding family of proteins implicated in the regulation of ion conductances, Ca(2+) homeostasis, and membrane trafficking...
  43. Naciff J, Kaetzel M, Behbehani M, Dedman J. Differential expression of annexins I-VI in the rat dorsal root ganglia and spinal cord. J Comp Neurol. 1996;368:356-70 pubmed
    ..The differential localization pattern of annexins in cells of the SC and DRG could reflect their individual biological roles in Ca(2+)-signal transduction within the central nervous system. ..
  44. Wang J, Liu Y, Zheng Y, Lin F, Cai G, Yao X. Comparative proteomics analysis of colorectal cancer. Asian Pac J Cancer Prev. 2012;13:1663-6 pubmed
    ..twelve protein spots were identified using mass spectrometry, of which 8 were up-regulated, including HSPB1 and Annexin A4, while 4 were down-regulated, the results being consistent with Western blot findings...
  45. Masuishi Y, Arakawa N, Kawasaki H, Miyagi E, Hirahara F, Hirano H. Wild-type p53 enhances annexin IV gene expression in ovarian clear cell adenocarcinoma. FEBS J. 2011;278:1470-83 pubmed publisher
    ..Therefore, we conclude that the ANX4 gene is a direct transcriptional target of p53, and its expression is enhanced by wild-type p53 in CCA cells. ..
  46. Diakonova M, Gerke V, Ernst J, Liautard J, van der Vusse G, Griffiths G. Localization of five annexins in J774 macrophages and on isolated phagosomes. J Cell Sci. 1997;110 ( Pt 10):1199-213 pubmed
    ..Because of their purity and ease of preparation we suggest that phagosomes are a powerful system to study the potential role of annexins in membrane traffic. ..
  47. Wei R, Xie Y, Yang D, He L, Peng F, Sheng L. [Differential proteomic analysis of drug resistant A549/DDP cell lines in human lung adenocarcinoma]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35:854-60 pubmed publisher
    ..Western blot showed that heat shock protein beta-1, annexin A4, cofilin l, vimentin were differential expression proteins in A549 and A549/DDP, which was consistent with the ..
  48. Zou D, Brewer M, Garcia F, Feugang J, Wang J, Zang R, et al. Cactus pear: a natural product in cancer chemoprevention. Nutr J. 2005;4:25 pubmed
    ..To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model...
  49. Sohma H, Ohkawa H, Hashimoto E, Sakai R, Saito T. Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human A549 adenocarcinoma cells. Alcohol Clin Exp Res. 2002;26:44S-48S pubmed
    ..The amount of annexin IV seemed to increase before the induction of cell damage by ethanol. Annexin IV might be one of the specific markers for the effect of ethanol. ..
  50. Takagi H, Asano Y, Yamakawa N, Matsumoto I, Kimata K. Annexin 6 is a putative cell surface receptor for chondroitin sulfate chains. J Cell Sci. 2002;115:3309-18 pubmed
    ..In summary, annexin 6 is a candidate receptor for chondroitin sulfate chains. ..
  51. 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. ..
  52. Kundranda M, Ray S, Saria M, Friedman D, Matrisian L, Lukyanov P, et al. Annexins expressed on the cell surface serve as receptors for adhesion to immobilized fetuin-A. Biochim Biophys Acta. 2004;1693:111-23 pubmed
    ..Our studies suggest that the expression of annexin-II and -VI and possibly other members of the family mediate novel adhesion and signaling mechanisms in tumor cells. ..
  53. Zernii E, Tikhomirova N, Philippov P, Senin I. Detection of annexin IV in bovine retinal rods. Biochemistry (Mosc). 2003;68:129-60 pubmed
    ..In immunoblot, annexin IV purified from bovine rod outer segments cross-reacted with antibodies against annexin IV from bovine liver. This is the first detection of annexin IV in vertebrate retina. ..