Annexin A5

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.

ANXA5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesANXA5, ANX5, ENX2, HEL-S-7, PP4, RPRGL3, annexin A5, CPB-I, VAC-alph
External IDsOMIM: 131230 MGI: 106008 HomoloGene: 20312 GeneCards: ANXA5
Orthologs
SpeciesHumanMouse
Entrez

308

11747

Ensembl

ENSG00000164111

ENSMUSG00000027712

UniProt

P08758

P48036

RefSeq (mRNA)

NM_001154

NM_009673

RefSeq (protein)

NP_001145

NP_033803

Location (UCSC)Chr 4: 121.67 – 121.7 MbChr 3: 36.5 – 36.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[6][7][8] 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.[9] Detection occurs by flow cytometry or a fluorescence microscope.

Interactions

Annexin A5 has been shown to interact with Kinase insert domain receptor[10] and Integrin, beta 5.[11]

References

  1. GRCh38: Ensembl release 89: ENSG00000164111 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027712 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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 (Apr 2012). "Proteomic profiling of follicular and papillary thyroid tumors". European Journal of Endocrinology. 166 (4): 657–67. doi:10.1530/EJE-11-0856. PMC 3315832. PMID 22275472.
  6. 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.
  7. Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH (Sep 1994). "Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis". Blood. 84 (5): 1415–20. doi:10.1182/blood.V84.5.1415.bloodjournal8451415. PMID 8068938.
  8. Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (Jul 1995). "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. doi:10.1016/0022-1759(95)00072-I. PMID 7622868.
  9. Annexin-FP488 fluorescent staining protocol at Interchim
  10. Wen Y, Edelman JL, Kang T, Sachs G (May 1999). "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. doi:10.1006/bbrc.1999.0678. PMID 10329451.
  11. Cardó-Vila M, Arap W, Pasqualini R (May 2003). "Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V". Molecular Cell. 11 (5): 1151–62. doi:10.1016/S1097-2765(03)00138-2. PMID 12769841.

Further reading

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