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 PDB Ortholog search: PDBe RCSB List of PDB id codes 2XO3, 1ANW, 1ANX, 1AVH, 1AVR, 1HAK, 1HVD, 1HVE, 1HVF, 1HVG, 1SAV, 2XO2
Identifiers
Aliases	ANXA5, ANX5, ENX2, HEL-S-7, PP4, RPRGL3, annexin A5, CPB-I, VAC-alph
External IDs	OMIM: 131230; MGI: 106008; HomoloGene: 20312; GeneCards: ANXA5; OMA:ANXA5 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q27 Start 121,667,946 bp[1] End 121,696,995 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 B|3 17.46 cM Start 36,503,072 bp[2] End 36,530,043 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium smooth muscle tissue Achilles tendon right lung canal of the cervix gallbladder monocyte Descending thoracic aorta ascending aorta islet of Langerhans Top expressed in utricle vestibular membrane of cochlear duct stroma of bone marrow right lung lobe vestibular sensory epithelium calvaria molar dermis umbilical cord white adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phospholipase inhibitor activity calcium ion binding protein binding calcium-dependent phospholipid binding phospholipid binding P-type calcium transporter activity heparin binding peptide hormone binding receptor tyrosine kinase binding molecular adaptor activity Cellular component membrane focal adhesion intracellular anatomical structure endothelial microparticle extracellular exosome external side of plasma membrane extracellular region cytoplasm cytosol collagen-containing extracellular matrix Biological process hemostasis negative regulation of coagulation blood coagulation negative regulation of apoptotic process response to organic substance signal transduction negative regulation of catalytic activity platelet degranulation negative regulation of blood coagulation positive regulation of apoptotic process protein homooligomerization negative regulation of sequestering of calcium ion response to calcium ion calcium ion transmembrane transport cellular response to lead ion response to thyroid hormone cellular response to gonadotropin-releasing hormone regulation of flagellated sperm motility negative regulation of prolactin secretion Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 3: 36.5 – 36.53 Mb PubMed search [3] [4]
Wikidata
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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]