Annexin A5

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.{{cite journal | vauthors = Sofiadis A, Becker S, Hellman U, Hultin-Rosenberg L, Dinets A, Hulchiy M, Zedenius J, Wallin G, Foukakis T, Höög A, Auer G, Lehtiö J, Larsson C | title = Proteomic profiling of follicular and papillary thyroid tumors | journal = European Journal of Endocrinology| volume = 166 | issue = 4 | pages = 657–67 | date = Apr 2012 | pmid = 22275472 | doi = 10.1530/EJE-11-0856 | pmc=3315832}}

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.{{cite journal|author=Meers P and Mealy T |year=1994|title= Phospholipid determinants for annexin V binding sites and the role of tryptophan|journal=Biochemistry|volume=33|issue=19|pages= 5829–37|doi=10.1021/bi00185a022|pmid=8180211}}{{cite journal | vauthors = Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH | title = Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis | journal = Blood | volume = 84 | issue = 5 | pages = 1415–20 | date = Sep 1994 | doi = 10.1182/blood.V84.5.1415.1415 | pmid = 8068938 | doi-access = }}{{cite journal | vauthors = Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C | title = A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V | journal = Journal of Immunological Methods | volume = 184 | issue = 1 | pages = 39–51 | date = Jul 1995 | pmid = 7622868 | doi = 10.1016/0022-1759(95)00072-I | url = 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 }} 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.[http://www.interchim.fr/ft/B/BH4140.pdf Annexin-FP488 fluorescent staining protocol] at Interchim Detection occurs by flow cytometry or a fluorescence microscope.

Annexin A5 has been shown to interact with Kinase insert domain receptor{{cite journal | vauthors = Wen Y, Edelman JL, Kang T, Sachs G | title = Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1 | journal = Biochemical and Biophysical Research Communications | volume = 258 | issue = 3 | pages = 713–21 | date = May 1999 | pmid = 10329451 | doi = 10.1006/bbrc.1999.0678 | url = https://zenodo.org/record/1229498 }} and Integrin, beta 5.{{cite journal | vauthors = Cardó-Vila M, Arap W, Pasqualini R | title = Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V | journal = Molecular Cell | volume = 11 | issue = 5 | pages = 1151–62 | date = May 2003 | pmid = 12769841 | doi = 10.1016/S1097-2765(03)00138-2 | doi-access = free }}

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{{Reflist|33em}}

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• {{cite journal | vauthors = Huber R, Berendes R, Burger A, Schneider M, Karshikov A, Luecke H, Römisch J, Paques E | title = 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 = Journal of Molecular Biology | volume = 223 | issue = 3 | pages = 683–704 | date = Feb 1992 | pmid = 1311770 | doi = 10.1016/0022-2836(92)90984-R }}
• {{cite journal | vauthors = Kirsch T, Pfäffle M | title = 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 | journal = FEBS Letters | volume = 310 | issue = 2 | pages = 143–7 | date = Sep 1992 | pmid = 1397263 | doi = 10.1016/0014-5793(92)81316-E | s2cid = 9498732 | doi-access = free }}
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• {{cite journal | vauthors = Ahn NG, Teller DC, Bienkowski MJ, McMullen BA, Lipkin EW, de Haën C | title = Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor | journal = The Journal of Biological Chemistry | volume = 263 | issue = 35 | pages = 18657–63 | date = Dec 1988 | doi = 10.1016/S0021-9258(18)37335-6 | pmid = 2974032 | doi-access = free }}
• {{cite journal | vauthors = Demange P, Voges D, Benz J, Liemann S, Göttig P, Berendes R, Burger A, Huber R | title = Annexin V: the key to understanding ion selectivity and voltage regulation? | journal = Trends in Biochemical Sciences | volume = 19 | issue = 7 | pages = 272–6 | date = Jul 1994 | pmid = 7519374 | doi = 10.1016/0968-0004(94)90002-7 }}
• {{cite journal | vauthors = Fernández MP, Morgan RO, Fernández MR, Carcedo MT | title = The gene encoding human annexin V has a TATA-less promoter with a high G+C content | journal = Gene | volume = 149 | issue = 2 | pages = 253–60 | date = Nov 1994 | pmid = 7958998 | doi = 10.1016/0378-1119(94)90157-0 }}

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• {{MeshName|Annexin+A5}}
• {{UCSC gene info|ANXA5}}

{{PDB Gallery|geneid=308}}

{{Calcium-binding proteins}}

Category:Peripheral membrane proteins