Annexin A5
Annexin A5 (or annexin V) is a cellular protein in the annexin group. 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.
Annexin A5 in 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.
Laboratory use of annexin A5
Annexin A5 is used as a probe in the annexin A5 affinity assay to detect cells that have expressed phosphatidylserine on the cell surface, a feature found in apoptosis as well as other forms of cell death.[1][2] Platelets also expose phosphatidylserine on their surface when activated, which serves as binding site for various coagulation factors.
Interactions
Annexin A5 has been shown to interact with Kinase insert domain receptor[3] and Integrin, beta 5.[4]
References
- ^ Koopman G, Reutelingsperger CP, Kuijten GAM et al. (1994). "Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis". Blood 84 (5): 1415–20. PMID 8068938.
- ^ Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (1995). "A novel assay for apoptosis—flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V". J Immunol Methods 184 (1): 39–51. doi:10.1016/0022-1759(95)00072-I. PMID 7622868.
- ^ Wen, Y; Edelman J L, Kang T, Sachs G (May. 1999). "Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1". Biochem. Biophys. Res. Commun. (UNITED STATES) 258 (3): 713–21. doi:10.1006/bbrc.1999.0678. ISSN 0006-291X. PMID 10329451.
- ^ Cardó-Vila, Marina; Arap Wadih, Pasqualini Renata (May. 2003). "Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V". Mol. Cell (United States) 11 (5): 1151–62. doi:10.1016/S1097-2765(03)00138-2. ISSN 1097-2765. PMID 12769841.
Further reading
- Cederholm A, Frostegård J (2007). "Annexin A5 as a novel player in prevention of atherothrombosis in SLE and in the general population.". Ann. N. Y. Acad. Sci. 1108 (1): 96–103. doi:10.1196/annals.1422.011. PMID 17893975.
- Schlaepfer DD, Jones J, Haigler HT (1992). "Inhibition of protein kinase C by annexin V.". Biochemistry 31 (6): 1886–91. doi:10.1021/bi00121a043. PMID 1310621.
- Huber R, Berendes R, Burger A, et al. (1992). "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.". J. Mol. Biol. 223 (3): 683–704. doi:10.1016/0022-2836(92)90984-R. PMID 1311770.
- Kirsch T, Pfäffle M (1992). "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 Lett. 310 (2): 143–7. doi:10.1016/0014-5793(92)81316-E. PMID 1397263.
- Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- Tait JF, Frankenberry DA, Shiang R, et al. (1992). "Chromosomal localization of the human gene for annexin V (placental anticoagulant protein I) to 4q26----q28.". Cytogenet. Cell Genet. 57 (4): 187–92. doi:10.1159/000133143. PMID 1683830.
- Huber R, Römisch J, Paques EP (1991). "The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes.". EMBO J. 9 (12): 3867–74. PMC 552154. PMID 2147412. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=552154.
- Huber R, Schneider M, Mayr I, et al. (1991). "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 Lett. 275 (1-2): 15–21. doi:10.1016/0014-5793(90)81428-Q. PMID 2148156.
- Maurer-Fogy I, Reutelingsperger CP, Pieters J, et al. (1988). "Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+-dependent phospholipid-binding protein.". Eur. J. Biochem. 174 (4): 585–92. doi:10.1111/j.1432-1033.1988.tb14139.x. PMID 2455636.
- Rothhut B, Coméra C, Cortial S, et al. (1990). "A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation.". Biochem. J. 263 (3): 929–35. PMC 1133519. PMID 2532007. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1133519.
- Schlaepfer DD, Mehlman T, Burgess WH, Haigler HT (1987). "Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein.". Proc. Natl. Acad. Sci. U.S.A. 84 (17): 6078–82. doi:10.1073/pnas.84.17.6078. PMC 299011. PMID 2957692. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299011.
- Funakoshi T, Heimark RL, Hendrickson LE, et al. (1987). "Human placental anticoagulant protein: isolation and characterization.". Biochemistry 26 (17): 5572–8. doi:10.1021/bi00391a053. PMID 2960376.
- Iwasaki A, Suda M, Nakao H, et al. (1988). "Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placenta: a new lipocortin-like protein.". J. Biochem. 102 (5): 1261–73. PMID 2963810.
- Funakoshi T, Hendrickson LE, McMullen BA, Fujikawa K (1988). "Primary structure of human placental anticoagulant protein.". Biochemistry 26 (25): 8087–92. doi:10.1021/bi00399a011. PMID 2964863.
- Kaplan R, Jaye M, Burgess WH, et al. (1988). "Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein.". J. Biol. Chem. 263 (17): 8037–43. PMID 2967291.
- Grundmann U, Abel KJ, Bohn H, et al. (1988). "Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family.". Proc. Natl. Acad. Sci. U.S.A. 85 (11): 3708–12. doi:10.1073/pnas.85.11.3708. PMC 280287. PMID 2967495. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=280287.
- Pepinsky RB, Tizard R, Mattaliano RJ, et al. (1988). "Five distinct calcium and phospholipid binding proteins share homology with lipocortin I.". J. Biol. Chem. 263 (22): 10799–811. PMID 2968983.
- Ahn NG, Teller DC, Bienkowski MJ, et al. (1989). "Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor.". J. Biol. Chem. 263 (35): 18657–63. PMID 2974032.
- Demange P, Voges D, Benz J, et al. (1994). "Annexin V: the key to understanding ion selectivity and voltage regulation?". Trends Biochem. Sci. 19 (7): 272–6. doi:10.1016/0968-0004(94)90002-7. PMID 7519374.
- Fernández MP, Morgan RO, Fernández MR, Carcedo MT (1994). "The gene encoding human annexin V has a TATA-less promoter with a high G+C content.". Gene 149 (2): 253–60. doi:10.1016/0378-1119(94)90157-0. PMID 7958998.
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PDB gallery
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1a8a: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOSERINE
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1a8b: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOETHANOLAMINE
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1anw: THE EFFECT OF METAL BINDING ON THE STRUCTURE OF ANNEXIN V AND IMPLICATIONS FOR MEMBRANE BINDING
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1anx: THE CRYSTAL STRUCTURE OF A NEW HIGH-CALCIUM FORM OF ANNEXIN V
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1avh: 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
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1avr: 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
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1bc0: RECOMBINANT RAT ANNEXIN V, W185A MUTANT
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1bc1: RECOMBINANT RAT ANNEXIN V, QUADRUPLE MUTANT (T72K, S144K, S228K, S303K)
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1bc3: RECOMBINANT RAT ANNEXIN V, TRIPLE MUTANT (T72K, S144K, S228K)
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1bcw: RECOMBINANT RAT ANNEXIN V, T72A MUTANT
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1bcy: RECOMBINANT RAT ANNEXIN V, T72K MUTANT
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1bcz: RECOMBINANT RAT ANNEXIN V, T72S MUTANT
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1g5n: ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES
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1hak: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLACENTAL ANNEXIN V COMPLEXED WITH K-201 AS A CALCIUM CHANNEL ACTIVITY INHIBITOR
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1hvd: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
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1hve: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
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1hvf: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
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1hvg: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
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1n41: Crystal Structure of Annexin V K27E Mutant
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1n42: Crystal Structure of Annexin V R149E Mutant
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1n44: Crystal Structure of Annexin V R23E Mutant
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1sav: HUMAN ANNEXIN V WITH PROLINE SUBSTITUTION BY THIOPROLINE
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2ie6: Annexin V under 2.0 MPa pressure of xenon
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2ie7: Annexin V under 2.0 MPa pressure of nitrous oxide
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2ran: RAT ANNEXIN V CRYSTAL STRUCTURE: CA2+-INDUCED CONFORMATIONAL CHANGES
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External links
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| Cell membrane |
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Intracellular signaling
& calc. regulation |
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Calcium-binding
protein domains |
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| Extracellular ligands |
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| Calcium-binding proteins |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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