Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CAP-50 is a member of annexin family proteins which binds specifically to calcyclin in a Ca2+ dependent manner (Tokumitsu. H., Mizutani. A., Minami. H., Kobayashi. R., and Hidaka. H. (1992) J. Biol. Chem. 267,8919-8924). The cDNA representing the rabbit form of this protein has been cloned from rabbit lung cDNA library. Sequence analysis of two overlapping clones revealed a 81-nucleotides 5'-nontranslated region, 1512-nucleotides of open reading frame, a 672-nucleotides 3'-nontranslated region, and a poly(A) tail. Authenticity of the clones was confirmed by comparison of portions of the deduced amino acid sequence with eight sequences of proteolytic peptides obtained from rabbit lung protein. CAP-50 cDNA encodes a 503 residue protein with a calculated M(r) of 54,043 and shows that the protein is composed of four imperfect repeats and hydrophobic N-terminal region. C-terminal region including four imperfect repeats shows 58.1% identity with human synexin (annexin VII), 48.0% identity with annexin I, 47.4% identity with annexin II, 60.1% identity with annexin IV, 54.5% identity with annexin V. Hydrophobic N-terminal region composed of 202 amino acid residues is not homologous with other annexin proteins suggesting that CAP-50 is a novel member of annexin family proteins.
 ...
PMID:Molecular cloning of rabbit CAP-50, a calcyclin-associated annexin protein. 138 Jul 98

Annexins are a structurally related family of Ca2+ binding proteins of undertermined biological function. Annexin I (also called lipocortin 1) is a substrate for the EGF-stimulated tyrosine kinase and is postulated to be involved in mitogenic signal transduction. To investigate further the involvement of lipocortin 1 in cell proliferation, we measured lipocortin 1 levels in normal diploid human foreskin fibroblasts (HFF) to determine whether its expression changed as a function of growth status. For comparison, the expression of annexin V (also called endonexin II) was measured in HFF cells. Endonexin II is a protein with similar Ca2+ and phospholipid binding properties as lipocortin 1, but it is not a substrate for tyrosine kinases. Quiescent HFF cell cultures were induced to proliferate by either subculture to lower cell density, EGF stimulation, or serum stimulation. In all three protocols, proliferating HFF cells contained three- to fourfold higher levels of lipocortin 1 and three- to fourfold lower levels of endonexin II than quiescent HFF cells. In contrast, the expression of annexin II (also called calpactin I) and annexin IV (also called endonexin I) remained relatively unchanged in growing and quiescent HFF cells. Lipocortin 1 synthesis rate was eightfold higher and its turnover rate was 1.5-fold slower in proliferating compared to quiescent HFF cells. Endonexin II synthesis rate remained constant but its turnover rate was 2.2-fold faster in proliferating compared to quiescent HFF cells. In a separate set of experiments, annexin expression levels were measured in cultures of rat PC-12 cells, a pheochromocytoma that ceases proliferation and undergoes reversible differentiation into nondividing neuronlike cells in response to nerve growth factor (NGF). After NGF treatment, PC-12 cells expressed fivefold higher levels of endonexin II and 32-fold higher levels of calpactin 1. Lipocortin 1 and endonexin I were not expressed in PC-12 cells. In summary, lipocortin 1 expression exhibited a positive correlation with cell proliferation in HFF cells. The increased expression of endonexin II in quiescent HFF cells and differentiating PC-12 cells implies that this protein may play a more prominent role in nondividing cells.
 ...
PMID:Expression of annexins as a function of cellular growth state. 214 63

A cDNA library prepared from human placenta was screened for sequences encoding the placental protein 4 (PP4). PP4 is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. Partial amino acid sequence information from PP4-derived cyanogen bromide fragments was used to design three oligonucleotide probes for screening the library. From 10(6)independent recombinants, 18 clones were identified that hybridized to all three probes. These 18 recombinants contained cDNA inserts encoding a protein of 320 amino acid residues. In addition to the PP4 cDNA we identified 9 other recombinants encoding a protein with considerable similarity (74%) TO PP4, which was termed PP4-X. PP4 and PP4-X belong to the lipocortin family, as judged by their homology to lipocortin I and calpactin I.
 ...
PMID:Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family. 296 95

This study addresses the roles of individual annexin IV domains in calcium-dependent membrane binding and aggregation through an analysis of the activities of mutant annexin IV proteins in which critical residues in one or more domains have been altered. The consensus sequence for high-affinity Ca(2+)-binding pockets obtained from the annexin V crystal structure is GXGT-38 residues-D/E [Huber, R., et al. (1992) J. Mol. Biol. 223, 683-704]. Site-directed mutagenesis was used to change the conserved acidic residues (D/E) in these sequences to alanine residues in each of the four domains of bovine annexin IV, singly or in combinations. Fourteen mutants with one, two, three, or four mutated domains were constructed and expressed in Escherichia coli. Purified recombinant product was evaluated for Ca(2+)-dependent binding to and aggregation of bovine chromaffin granules. Increases in the number of mutated domains resulted in increased Ca2+ requirements for both granule binding and aggregation. Further analysis revealed that mutations in individual domains had preferential effects on the binding or aggregating activities of the protein. For example, mutation of the first or fourth domains had a greater effect on membrane binding than aggregation, while conversely, mutation of the second domain had a more dramatic effect on membrane aggregation. Mutation of the third domain was largely silent in these assays. An additional mutation was made in the fourth domain to substitute a serine for a highly conserved arginine residue (Arg274) present at the C-terminus of the fourth endonexin fold. This mutation increased the calcium requirement for membrane binding 2-fold and for membrane aggregation 3-fold. This mutant protein was found to be an effective inhibitor of membrane aggregation by native annexin IV at intermediate levels of calcium.
 ...
PMID:Combinatorial mutagenesis of the four domains of annexin IV: effects on chromaffin granule binding and aggregating activities. 789 24

Endonexin (annexin IV) is a member of the annexin family of homologous proteins that bind membranes and aggregate vesicles in a calcium-dependent fashion. This study examines the lipid modulation and mechanism of the binding of endonexin to membranes using a fluorescence energy transfer assay to measure bovine endonexin binding to well-defined large unilamellar vesicles. The calcium sensitivity for endonexin-membrane binding is observed to be highly dependent on the types of membrane lipids present. As with most annexins, negatively charged lipids best promote endonexin binding to phosphatidylcholine (PC) containing membranes. However, a comparison of 11 different types of lipids reveals that other factors such as the type of ion contributing the charge and head-group size are also important. The concentrations of calcium required for half-maximal binding of endonexin to PC vesicles containing 30% phosphatidylserine (PS) or 30% phosphatidylinositol (PI), both lipids with net charge-1, are 48 +/- 6 and 114 +/- 19 microM, respectively, while half-maximal binding to 30% phosphatidylinositol bisphosphate (PIP2), with a greater net charge of -3 to -5, occurs at 65 microM calcium, similar to the calcium requirement for binding to PS. The apparent affinities of endonexin for seven different types of lipids parallel those reported for annexin V [Andree, H. A. M., Reutelingsperger, C. P. M., Hauptmann, R., Hemker, H. C., Hermans, W. T., & Willems, G. M. (1990) J. Biol. Chem. 265, 4923-4928], except for a greater preference of endonexin for membranes containing phosphatidic acid. Mixing PS and phosphatidylethanolamine (PE) or PS and PI in the same PC vesicle synergistically enhances endonexin-membrane binding, indicating that even lipids with no net charge such as PE may dramatically affect endonexin binding to mixed-lipid membranes. The maximum amount of endonexin able to bind to PS/PC vesicles at 1 mM calcium increases with mole % PS. A simple and general model that treats protein-membrane binding as a two-step process, with adsorption to a membrane surface followed by interaction with specific lipid molecules [Lentz, B. R., & Hermans, J. (1989) Biochemistry 28, 7459-7461], is extended to include the coupled binding of calcium with binding of specific lipid molecules. This extended model accurately predicts trends observed when protein and calcium titrations of endonexin binding to PS/PC vesicles are performed under a wide variety of conditions and suggests that 3-5 calcium ions and 9-18 PS molecules participate in each endonexin-membrane complex.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Ca(2+)-dependent binding of endonexin (annexin IV) to membranes: analysis of the effects of membrane lipid composition and development of a predictive model for the binding interaction. 804 80

Annexin V has been purified from chicken liver; 40 mg of annexin V was obtained per kg of tissue. In contrast with mammalian liver, very little annexin VI was obtained. Surprisingly, chicken liver annexin V resembles mammalian annexin IV in its M(r) (32,500) and its isoelectric point (5.6), but amino-acid-sequence analysis demonstrates identity with chicken annexin V (anchorin CII). It binds to phospholipids in a Ca(2+)-dependent manner with free-Ca2+ concentrations for half-maximal binding to phosphatidylserine and phosphatidic acid of 10 microM; phosphatidylethanolamine of 32 microM and phosphatidylinositol of 90 microM. No binding to phosphatidylcholine was observed at Ca2+ concentrations up to 300 microM. In isolated liver membranes a significant proportion of annexin V was not extractable with EGTA but could only be extracted with Triton X-100, suggesting the existence of a tightly membrane-associated form of annexin V. A specific antiserum to chicken annexin V was used to localize the protein in adult and embryonic chicken liver. In the adult, annexin V was highly concentrated in epithelial cells lining the bile ducts, and along the bile canaliculi. In embryonic liver, strong staining of the bile-duct epithelial cells was again evident, and in addition, endothelial cells were strongly immunoreactive.
 ...
PMID:Isolation, characterization and localization of annexin V from chicken liver. 848 40

The annexins are a family of Ca(2+)-dependent phospholipid-binding proteins. In the present study, the spatial expression patterns of annexins I-VI were evaluated in the rat dorsal root ganglia (DRG) and spinal cord (SC) by using indirect immunofluorescence. Annexin I is expressed in small sensory neurons of the DRG, by most neurons of the SC, and by ependymal cells lining the central canal. Annexin II is expressed by most sensory neurons of the DRG but is primarily expressed in the SC by glial cells. Annexin III is expressed by most sensory neurons, regardless of size, by endothelial cells lining the blood vessels, and by the perineurium. In the SC, annexin III is primarily expressed by astrocytes. In the DRG and the SC, annexin IV is primarily expressed by glial cells and at lower levels by neurons. In the DRG, annexin V is expressed in relatively high concentrations in small sensory neurons in contrast to the SC, where it is expressed mainly by ependymal cells and by small-diameter axons located in the superficial laminae of the dorsal horn areas. Annexin VI is differentially expressed by sensory neurons of the DRG, being more concentrated in small neurons. In the SC, annexin VI has the most striking distribution. It is concentrated subjacent to the plasma membrane of motor neurons and their processes. The differential localization pattern of annexins in cells of the SC and DRG could reflect their individual biological roles in Ca(2+)-signal transduction within the central nervous system.
 ...
PMID:Differential expression of annexins I-VI in the rat dorsal root ganglia and spinal cord. 872 44

In cell culture, human osteoblasts and the osteosarcoma cell line MG-63 express annexins I, II, IV, V and VI. Small proportions of annexins IV and V are lost from MG-63 cells into the culture medium in a sedimentable form. however, the bulk of these annexins is intracellular. In non-confluent cells 3 days after passaging, annexin IV and annexin V are strongly present throughout the nucleus and are also present in the cytoplasm. On elevation of the intracellular calcium concentration with the lonophore ionomycin, the intranuclear pools of annexin IV in 38 +/- 4% of cells and annexin V in 70 +/- 5% of cells show relocation to the nuclear membrane within 40 s. Extracellular ATP, which causes a transient increase in the cytosolic free calcium concentration by acting at P2-purinoceptors, also causes relocation of the intranuclear pool of annexin IV in 22 +/- 4% of cells and of annexin V in 38 +/- 8% of cells. After stimulation no significant reversal of the relocation is observed. Elevation of intracellular calcium with ionophore and ATP also causes relocation of the cytoplasmic pools of annexins IV and V. The results support a role for annexins at cellular membranes in response to elevation of cytosolic calcium levels.
 ...
PMID:Calcium-induced relocation of annexins IV and V in the human osteosarcoma cell line MG-63. 874 77

Following incubation of human fibroblasts with Ca2+ ionophore A23187, we found strong immunofluorescence labelling of the nuclear envelope by annexin IV antibody. Using confocal imaging of cells loaded with Fluo-3, we showed that A23187 generates an intense and sustained rise of Ca2+ in the nucleus. By contrast, stimulation without extracellular Ca2+ produces only a brief rise in nuclear Ca2+ that does not promote annexin IV translocation to the nuclear envelope, and compounds that induce only a transient increase of nuclear Ca2+ do not support translocation of annexin IV. In addition, annexin V was also translocated to the nuclear envelope by A23187, but distribution of annexins I, II, VI and VII is unaffected. In in vitro assays with isolated nuclei, annexin V was also found to bind to the nuclear envelope in a Ca2+-dependent manner. These results demonstrate that the translocation to the nuclear envelope of different types of Ca2+-regulated proteins is directly triggered by a major rise of Ca2+ in the nucleus.
 ...
PMID:A rise in nuclear calcium translocates annexins IV and V to the nuclear envelope. 877 58

Annexins are a family of proteins implicated in a number of cellular processes involving calcium. We studied annexins I, II, IV, V and VI and found that they are all present in human foreskin fibroblasts and, from immunocytochemical studies, have distinct locations in the cell. Only annexin IV and annexin V have unstructured cytoplasmic staining patterns consistent with predominantly cytosolic locations. Annexin VI partially colocalizes with the endoplasmic reticulum. In contrast, annexins I and II are both associated with the plasma membrane with annexin II having a very homogeneous staining compared with the punctate pattern observed for annexin I. Annexins I, IV and V are all present in the nucleus at higher concentrations than in the cytoplasm. Treatment of cells with the calcium ionophore A23187 to raise intracellular calcium, results in relocations of annexin II, IV, V and VI. Intranuclear annexins IV and V relocate to the nuclear membrane whereas the cytosolic pools of these annexins relocate to the plasma membrane. Annexin II relocates to granular structures at the plasma membrane whereas annexin VI relocates to a more homogeneous distribution on the plasma membrane. These results are consistent with an important role for annexins in mediating the calcium signal at the plasma membrane and within the nuclei of fibroblasts.
 ...
PMID:Annexins II, IV, V and VI relocate in response to rises in intracellular calcium in human foreskin fibroblasts. 883 9


1 2 Next >>