Biology:Annexin A5

Short description: Protein-coding gene in the species Homo sapiens

Annexin A5 (or annexin V) is a cellular protein in the annexin group. In flow cytometry, annexin V is commonly used to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane. The function of the protein is unknown; however, annexin A5 has been proposed to play a role in the inhibition of blood coagulation by competing for phosphatidylserine binding sites with prothrombin and also to inhibit the activity of phospholipase A1. These properties have been found by in vitro experiments.

Pathology

Antibodies directed against annexin A5 are found in patients with a disease called the antiphospholipid syndrome (APS), a thrombophilic disease associated with autoantibodies against phospholipid compounds.

Annexin A5 forms a shield around negatively charged phospholipid molecules. The formation of an annexin A5 shield blocks the entry of phospholipids into coagulation (clotting) reactions. In the antiphospholipid antibody syndrome, the formation of the shield is disrupted by antibodies. Without the shield, there is an increased quantity of phospholipid molecules on cell membranes, speeding up coagulation reactions and causing the blood-clotting characteristic of the antiphospholipid antibody syndrome.
Annexin A5 showed upregulation in papillary thyroid carcinoma.^[1]

Laboratory use

Annexin A5 is used as a non-quantitative probe to detect cells that have expressed phosphatidylserine (PS) on the cell surface, an event found in apoptosis as well as other forms of cell death.^[2]^[3]^[4] Platelets also expose PS and PE on their surface when activated, which serves as binding site for various coagulation factors.

The annexin A5 affinity assay typically uses a conjugate of annexin V and a fluorescent or enzymatic label, biotin or other tags, or a radioelement, in a suitable buffer (annexin V binding to aminophospholipids is Ca²⁺ dependent). The assay combines annexin V staining of PS and PE membrane events with the staining of DNA in the cell nucleus with propidium iodide (PI) or 7-Aminoactinomycin D (AAD-7), distinguishing viable cells from apoptotic cells and necrotic cells.^[5] Detection occurs by flow cytometry or a fluorescence microscope.

Interactions

Annexin A5 has been shown to interact with Kinase insert domain receptor^[6] and Integrin, beta 5.^[7]

References

↑ "Proteomic profiling of follicular and papillary thyroid tumors". European Journal of Endocrinology 166 (4): 657–67. Apr 2012. doi:10.1530/EJE-11-0856. PMID 22275472.
↑ Meers P and Mealy T (1994). "Phospholipid determinants for annexin V binding sites and the role of tryptophan". Biochemistry 33 (19): 5829–37. doi:10.1021/bi00185a022. PMID 8180211.
↑ "Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis". Blood 84 (5): 1415–20. Sep 1994. doi:10.1182/blood.V84.5.1415.bloodjournal8451415. PMID 8068938.
↑ "A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V". Journal of Immunological Methods 184 (1): 39–51. Jul 1995. doi:10.1016/0022-1759(95)00072-I. PMID 7622868. https://research.utwente.nl/en/publications/a-novel-assay-for-apoptosis-flow-cytometric-detection-of-phosphatidylserine-expression-on-early-apoptotic-cells-using-fluorescein-labelled-annexine-v(7b04cbeb-878f-4652-a748-9cb7e9cd7b30).html.
↑ Annexin-FP488 fluorescent staining protocol at Interchim
↑ "Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1". Biochemical and Biophysical Research Communications 258 (3): 713–21. May 1999. doi:10.1006/bbrc.1999.0678. PMID 10329451. https://zenodo.org/record/1229498.
↑ "Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V". Molecular Cell 11 (5): 1151–62. May 2003. doi:10.1016/S1097-2765(03)00138-2. PMID 12769841.

"Annexin A5 as a novel player in prevention of atherothrombosis in SLE and in the general population". Annals of the New York Academy of Sciences 1108 (1): 96–103. Jun 2007. doi:10.1196/annals.1422.011. PMID 17893975.
"Inhibition of protein kinase C by annexin V". Biochemistry 31 (6): 1886–91. Feb 1992. doi:10.1021/bi00121a043. PMID 1310621.
"Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins". Journal of Molecular Biology 223 (3): 683–704. Feb 1992. doi:10.1016/0022-2836(92)90984-R. PMID 1311770.
"Selective binding of anchorin CII (annexin V) to type II and X collagen and to chondrocalcin (C-propeptide of type II collagen). Implications for anchoring function between matrix vesicles and matrix proteins". FEBS Letters 310 (2): 143–7. Sep 1992. doi:10.1016/0014-5793(92)81316-E. PMID 1397263.
"Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection 24 (3): 317–20. May 1992. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
"Chromosomal localization of the human gene for annexin V (placental anticoagulant protein I) to 4q26----q28". Cytogenetics and Cell Genetics 57 (4): 187–92. 1992. doi:10.1159/000133143. PMID 1683830.
"The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes". The EMBO Journal 9 (12): 3867–74. Dec 1990. doi:10.1002/j.1460-2075.1990.tb07605.x. PMID 2147412.
"The calcium binding sites in human annexin V by crystal structure analysis at 2.0 A resolution. Implications for membrane binding and calcium channel activity". FEBS Letters 275 (1–2): 15–21. Nov 1990. doi:10.1016/0014-5793(90)81428-Q. PMID 2148156.
"Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+-dependent phospholipid-binding protein". European Journal of Biochemistry 174 (4): 585–92. Jul 1988. doi:10.1111/j.1432-1033.1988.tb14139.x. PMID 2455636.
"A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation". The Biochemical Journal 263 (3): 929–35. Nov 1989. doi:10.1042/bj2630929. PMID 2532007.
"Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein". Proceedings of the National Academy of Sciences of the United States of America 84 (17): 6078–82. Sep 1987. doi:10.1073/pnas.84.17.6078. PMID 2957692.
"Human placental anticoagulant protein: isolation and characterization". Biochemistry 26 (17): 5572–8. Aug 1987. doi:10.1021/bi00391a053. PMID 2960376.
"Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placenta: a new lipocortin-like protein". Journal of Biochemistry 102 (5): 1261–73. Nov 1987. doi:10.1093/oxfordjournals.jbchem.a122165. PMID 2963810.
"Primary structure of human placental anticoagulant protein". Biochemistry 26 (25): 8087–92. Dec 1987. doi:10.1021/bi00399a011. PMID 2964863.
"Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein". The Journal of Biological Chemistry 263 (17): 8037–43. Jun 1988. doi:10.1016/S0021-9258(18)68438-8. PMID 2967291.
"Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family". Proceedings of the National Academy of Sciences of the United States of America 85 (11): 3708–12. Jun 1988. doi:10.1073/pnas.85.11.3708. PMID 2967495.
"Five distinct calcium and phospholipid binding proteins share homology with lipocortin I". The Journal of Biological Chemistry 263 (22): 10799–811. Aug 1988. doi:10.1016/S0021-9258(18)38041-4. PMID 2968983.
"Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor". The Journal of Biological Chemistry 263 (35): 18657–63. Dec 1988. doi:10.1016/S0021-9258(18)37335-6. PMID 2974032.
"Annexin V: the key to understanding ion selectivity and voltage regulation?". Trends in Biochemical Sciences 19 (7): 272–6. Jul 1994. doi:10.1016/0968-0004(94)90002-7. PMID 7519374.
"The gene encoding human annexin V has a TATA-less promoter with a high G+C content". Gene 149 (2): 253–60. Nov 1994. doi:10.1016/0378-1119(94)90157-0. PMID 7958998.

External links

Annexin+A5 at the US National Library of Medicine Medical Subject Headings (MeSH)
Human ANXA5 genome location and ANXA5 gene details page in the UCSC Genome Browser.