Disease relevance of ANXA11

• Annexin XI, a member of the Ca2+-dependent, phospholipid-binding protein family, is an example of such a protein and was used in studies to devise a strategy using human autoimmune phage display libraries to generate reagents for biological studies of conserved cellular proteins [1].
• An IgG phage display library was generated from bone marrow of an autoimmune patient with high serum antibody titer against annexin XI, which was identified recently as an autoantigen targeted by autoantibodies in several systemic autoimmune diseases [1].
• Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features [2].
• The other three genes were annexin XI, human HIV Rev-interacting protein Rip-1, and the human homologue of the ATP-binding arsA component of the bacterial arsenite transporter, all of which are known to be widely expressed in human tissues [3].
• Anti-56K/annexin XI autoantibodies were found in a substantial number of patient sera (4.1-10.1%), but are rarely detected in sera from healthy controls and from patients with infectious diseases [4].

High impact information on ANXA11

• Searching among known proteins, each one of the amino acid sequences was found to share sequence similarity to annexin XI [5].
• Calcyclin, found previously to bind annexin XI in vitro, in vivo coated the nuclear membrane of cultured cell lines and did not colocalize with annexin XI [1].
• In metaphase, annexin XI was up-regulated and costained with alpha-tubulin [1].
• The subcellular distribution of annexin XI in COS-7 cells was shown to be Ca2+-dependent, and exhibited a predominantly nuclear pattern at low concentrations and a cytoplasmic pattern at high Ca2+ concentrations [1].
• Ultrastructural analysis by immunoelectron microscopy revealed that annexin XI associated with specific granules in both neutrophils and eosinophils, suggesting a role in the exocytotic pathway [1].

Biological context of ANXA11

• Mouse annexin A11 genomic clones were characterized by restriction analysis, Southern blotting, and DNA sequencing, and the homologous human gene (HGMW-approved gene symbol ANXA11) was deciphered from high-throughput genomic sequence with coanalysis of expressed sequence tags [6].
• Patients' sera recognize preferentially the N-terminal region of the protein, which is specific for 56K/annexin XI and not shared by other annexins, indicating that the autoimmune response to 56K/annexin XI in these patients is specific for this annexin family member [7].
• Genomic locations of ANX11 and ANX13 and the evolutionary genetics of human annexins [8].
• Our results illuminate the multifunctional nature of human annexin XI, provide the first evidence that annexin XI associates with the mitotic spindles and might play a role in cell division, and clearly illustrate the potential of phage display-derived human autoantibodies in broader analyses of the function of highly conserved cellular proteins [1].
• We examined the binding of CAP-50 to other Ca(2+)-binding proteins which have two of four EF-hand structures, by a co-precipitation assay with phospholipid (phosphatidylserine) [9].

Anatomical context of ANXA11

• Annexins VII, VI, III, and I respond to particle ingestion by translocating to phagosomes and other cell membrane structures, whereas annexin XI translocates predominantly to phagosomes, suggesting dissimilarities in their function [10].
• Moreover, several additional proteins were shown to be secreted by activated neutrophils, namely calgranulins, human cartilage glycoprotein of 39 kDa (HC gp-39), chitotriosidase, and annexin XI [11].
• In an earlier study, annexin XI was found to be present in the cytosol of neutrophil granulocytes (Blood (1996) 87, 4817) [12].

Associations of ANXA11 with chemical compounds

• For 4-week treatments, the patients received nicardipine (NIC) 20 mg t.i.d., CAP 50 mg b.i.d., NIC plus CAP, and matched placebo [13].
• Annexin V was found to be stable to intrinsic lung proteases in the presence of either Ca2+ or EGTA while annexin XI was found to be partially degraded by intrinsic lung proteases in the presence of EGTA [14].

Physical interactions of ANXA11

• Among nine Ca(2+)-binding proteins (calcyclin, S-100 proteins, p11, calgizzarin, calvasculin, calmodulin and troponin C) examined, only calcyclin interacted with CAP-50 [9].

Other interactions of ANXA11

• By yeast two-hybrid screening using human ALG-2 as bait, we isolated a cDNA of a novel ALG-2-interacting protein, which turned out to be annexin XI [15].
• The penta-EF-hand domain of ALG-2 interacts with amino-terminal domains of both annexin VII and annexin XI in a Ca2+-dependent manner [16].
• The 56K autoantigen is identical to human annexin XI [7].

Analytical, diagnostic and therapeutic context of ANXA11

• Confocal microscopy showed a cell cycle-specific redistribution of annexin XI from the cytoplasm to the mitotic spindle [1].
• In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases [2].
• Immunoblotting showed that annexin XI translocated to specific granules and secretory vesicles/plasma membrane at 100 micromol/l calcium [12].

References