Annexin A2 Explained

Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene.^[1]

Annexin 2 is involved in diverse cellular processes such as cell motility (especially that of the epithelial cells), linkage of membrane-associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and cell matrix interactions.It is a calcium-dependent phospholipid-binding protein whose function is to help organize exocytosis of intracellular proteins to the extracellular domain. Annexin II is a pleiotropic protein meaning that its function is dependent on place and time in the body.

Gene

The ANXA2 gene, located at 15q22.2, has three pseudogenes located on chromosomes 4, 9 and 10, respectively. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.^[2]

Function

This protein is a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption.^[2] Epigenetic regulation of Annexin A2 has been identified as a key determinant of mesenchymal transformation in brain tumors.^[3] Maternal deficiency of the ANXA2 gene contributes to shallow decidual invasion by placental cytotrophoblast cells. These findings highlight the maternal contribution to the pathogenesis of severe preeclampsia.^[4]

Annexin A2 has been proposed to function inside the cell in sorting of endosomes and outside the cell in anticoagulant reactions.

Interactions

Annexin A2 has been shown to interact with Prohibitin,^[5] CEACAM1,^[6] S100A10,^{[7] [8]} PCNA,^[9] complement Factor H,^[10] and a number of viral factors including the HPV16 minor capsid protein L2.^{[11] [12]}

See also

• Annexin

Further reading

• Kwon M, MacLeod TJ, Zhang Y, Waisman DM . S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors . Frontiers in Bioscience . 10 . 1–3 . 300–325 . January 2005 . 15574370 . 10.2741/1529 . free .
• Babiychuk EB, Draeger A . Regulation of ecto-5'-nucleotidase activity via Ca2+-dependent, annexin 2-mediated membrane rearrangement? . Biochemical Society Transactions . 34 . Pt 3 . 374–376 . June 2006 . 16709165 . 10.1042/BST0340374 .
• Bohn E, Gerke V, Kresse H, Löffler BM, Kunze H . Annexin II inhibits calcium-dependent phospholipase A1 and lysophospholipase but not triacyl glycerol lipase activities of rat liver hepatic lipase . FEBS Letters . 296 . 3 . 237–240 . January 1992 . 1531641 . 10.1016/0014-5793(92)80294-Q . 19633878 . free .
• Dawson SJ, White LA . Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin . The Journal of Infection . 24 . 3 . 317–320 . May 1992 . 1602151 . 10.1016/S0163-4453(05)80037-4 .
• Jindal HK, Chaney WG, Anderson CW, Davis RG, Vishwanatha JK . The protein-tyrosine kinase substrate, calpactin I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNA polymerase alpha . The Journal of Biological Chemistry . 266 . 8 . 5169–5176 . March 1991 . 1825830 . 10.1016/S0021-9258(19)67770-7 . free .
• Filipek A, Gerke V, Weber K, Kuźnicki J . Characterization of the cell-cycle-regulated protein calcyclin from Ehrlich ascites tumor cells. Identification of two binding proteins obtained by Ca2(+)-dependent affinity chromatography . European Journal of Biochemistry . 195 . 3 . 795–800 . February 1991 . 1999197 . 10.1111/j.1432-1033.1991.tb15768.x . free .
• Becker T, Weber K, Johnsson N . Protein-protein recognition via short amphiphilic helices; a mutational analysis of the binding site of annexin II for p11 . The EMBO Journal . 9 . 13 . 4207–4213 . December 1990 . 2148288 . 552202 . 10.1002/j.1460-2075.1990.tb07868.x .
• Spano F, Raugei G, Palla E, Colella C, Melli M . Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication . Gene . 95 . 2 . 243–251 . November 1990 . 2174397 . 10.1016/0378-1119(90)90367-Z .
• Johnsson N, Johnsson K, Weber K . A discontinuous epitope on p36, the major substrate of src tyrosine-protein-kinase, brings the phosphorylation site into the neighbourhood of a consensus sequence for Ca2+/lipid-binding proteins . FEBS Letters . 236 . 1 . 201–204 . August 1988 . 2456953 . 10.1016/0014-5793(88)80314-4 . 38734898 .
• Gould KL, Woodgett JR, Isacke CM, Hunter T . The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo . Molecular and Cellular Biology . 6 . 7 . 2738–2744 . July 1986 . 2946940 . 367834 . 10.1128/mcb.6.7.2738 .
• Huebner K, Cannizzaro LA, Frey AZ, Hecht BK, Hecht F, Croce CM, Wallner BP . Chromosomal localization of the human genes for lipocortin I and lipocortin II . Oncogene Research . 2 . 4 . 299–310 . May 1988 . 2969496 .
• Huang KS, Wallner BP, Mattaliano RJ, Tizard R, Burne C, Frey A, Hession C, McGray P, Sinclair LK, Chow EP . 6 . Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase . Cell . 46 . 2 . 191–199 . July 1986 . 3013422 . 10.1016/0092-8674(86)90736-1 . 24557024 .
• Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J . A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells . The Journal of Biological Chemistry . 269 . 12 . 9019–9023 . March 1994 . 7510700 . 10.1016/S0021-9258(17)37070-9 . free .
• Chung CY, Erickson HP . Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C . The Journal of Cell Biology . 126 . 2 . 539–548 . July 1994 . 7518469 . 2200039 . 10.1083/jcb.126.2.539 .
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T . 6 . Construction of a human full-length cDNA bank . Gene . 150 . 2 . 243–250 . December 1994 . 7821789 . 10.1016/0378-1119(94)90433-2 .
• Richard I, Broux O, Chiannilkulchai N, Fougerousse F, Allamand V, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C . 6 . Regional localization of human chromosome 15 loci . Genomics . 23 . 3 . 619–627 . October 1994 . 7851890 . 10.1006/geno.1994.1550 .
• Takahashi S, Reddy SV, Chirgwin JM, Devlin R, Haipek C, Anderson J, Roodman GD . Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption . The Journal of Biological Chemistry . 269 . 46 . 28696–28701 . November 1994 . 7961821 . 10.1016/S0021-9258(19)61961-7 . free .
• Hyatt SL, Liao L, Chapline C, Jaken S . Identification and characterization of alpha-protein kinase C binding proteins in normal and transformed REF52 cells . Biochemistry . 33 . 5 . 1223–1228 . February 1994 . 8110754 . 10.1021/bi00171a023 .
• Wright JF, Kurosky A, Wasi S . An endothelial cell-surface form of annexin II binds human cytomegalovirus . Biochemical and Biophysical Research Communications . 198 . 3 . 983–989 . February 1994 . 8117306 . 10.1006/bbrc.1994.1140 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .

Notes and References

1. Takahashi S, Reddy SV, Chirgwin JM, Devlin R, Haipek C, Anderson J, Roodman GD . Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption . The Journal of Biological Chemistry . 269 . 46 . 28696–28701 . November 1994 . 7961821 . 10.1016/S0021-9258(19)61961-7 . free .
2. Web site: Entrez Gene: ANXA2 annexin A2.
3. Kling T, Ferrarese R, Ó hAilín D, Johansson P, Heiland DH, Dai F, Vasilikos I, Weyerbrock A, Jörnsten R, Carro MS, Nelander S . 6 . Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma . eBioMedicine . 12 . 72–85 . October 2016 . 27667176 . 5078587 . 10.1016/j.ebiom.2016.08.050 .
4. Ng SW, Norwitz GA, Pavlicev M, Tilburgs T, Simón C, Norwitz ER . Endometrial Decidualization: The Primary Driver of Pregnancy Health . International Journal of Molecular Sciences . 21 . 11 . 4092 . June 2020 . 32521725 . 7312091 . 10.3390/ijms21114092 . free .
5. Bacher S, Achatz G, Schmitz ML, Lamers MC . Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2 . Biochimie . 84 . 12 . 1207–1220 . December 2002 . 12628297 . 10.1016/S0300-9084(02)00027-5 .
6. Kirshner J, Schumann D, Shively JE . CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II in a three-dimensional model of mammary morphogenesis . The Journal of Biological Chemistry . 278 . 50 . 50338–50345 . December 2003 . 14522961 . 10.1074/jbc.M309115200 . free .
7. Réty S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A . 6 . The crystal structure of a complex of p11 with the annexin II N-terminal peptide . Nature Structural Biology . 6 . 1 . 89–95 . January 1999 . 9886297 . 10.1038/4965 . 26400923 .
8. He KL, Deora AB, Xiong H, Ling Q, Weksler BB, Niesvizky R, Hajjar KA . Endothelial cell annexin A2 regulates polyubiquitination and degradation of its binding partner S100A10/p11 . The Journal of Biological Chemistry . 283 . 28 . 19192–19200 . July 2008 . 18434302 . 2443646 . 10.1074/jbc.M800100200 . free .
9. Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T . A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein . The Journal of Biological Chemistry . 277 . 43 . 40362–40367 . October 2002 . 12171929 . 10.1074/jbc.M206194200 . free .
10. Leffler J, Herbert AP, Norström E, Schmidt CQ, Barlow PN, Blom AM, Martin M . Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells . The Journal of Biological Chemistry . 285 . 6 . 3766–3776 . February 2010 . 19951950 . 2823518 . 10.1074/jbc.M109.045427 . free .
11. Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM . 6 . The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection . PLOS ONE . 7 . 8 . e43519 . 2012 . 22927980 . 3425544 . 10.1371/journal.pone.0043519 . 2012PLoSO...743519W . free .
12. Woodham AW, Raff AB, Raff LM, Da Silva DM, Yan L, Skeate JG, Wong MK, Lin YG, Kast WM . 6 . Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression . Journal of Immunology . 192 . 10 . 4748–4757 . May 2014 . 24719459 . 4019435 . 10.4049/jimmunol.1303190 .