Disease relevance of ANXA5

• These findings strongly indicate that human liver E-II is a very specific small HBsAg-binding protein and support the assumption that human liver E-II is the hepatitis B virus receptor protein [1].
• In situ hybridization identified anchorin CII also in the otic vesicle adjacent to the site of contact with the statoacoustic ganglion and in the mandibular mesenchyme [2].
• To determine if this rise in [Ca(2+)](i) functionally participates in the maturational process of growth plate chondrocytes (GPCs), we examined its effect on several markers of hypertrophy, including annexin V, bone morphogenetic protein-6, type X collagen, and indian hedgehog [3].
• Spontaneous development of anti-hepatitis B virus envelope (anti-idiotypic) antibodies in animals immunized with human liver endonexin II or with the F(ab')2 fragment of anti-human liver endonexin II immunoglobulin G: evidence for a receptor-ligand-like relationship between small hepatitis B surface antigen and endonexin II [1].
• Absence of cell-surface annexin V is accompanied by defective collagen matrix binding in the Swarm rat chondrosarcoma [4].

High impact information on ANXA5

• Northern blot and immunohistochemical analyses showed that the production and release of annexin V-rich matrix vesicles by mineralizing chondrocytes were accompanied by a marked increase in annexin V expression and, interestingly, were followed by increased expression of type I collagen [5].
• Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro-osseous mineralizing border exhibited expression of both annexin V and type I collagen [5].
• The amino acid sequence of anchorin CII, a collagen-binding protein isolated originally from chondrocyte membranes, was previously determined by sequencing of cDNA and proteolytic fragments of the protein [6].
• While these proteins have been located at the inner side of the plasma membrane of fibroblasts and epithelial cells, here we present experimental evidence that anchorin CII is at least partially released from cells and binds to the outer cell surface [6].
• Biosynthesis studies in cell-free systems and in cell culture indicate that anchorin CII is not processed, which is consistent with the absence of signal sequences from the protein [6].

Biological context of ANXA5

• The structure of anchorin CII, a collagen binding protein isolated from chondrocyte membrane [7].
• cDNA clones for anchorin CII (Mr = 34,000), a collagen-binding protein, were isolated from a lambda gt 11 cDNA library prepared from chick cartilage mRNA [8].
• 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) [9].
• The anchorin CII-encoding gene spans about 24 kb and consists of 13 exons ranging in length from 50 to 561 bp, interrupted by 12 introns of 94 bp to 7 kb [10].
• Potential binding sites for transcription factors in the 5'-upstream region are consistent with regulation of anx5 expression by mitogens, oncoproteins, steroids and possibly metals [10].

Anatomical context of ANXA5

• 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 [9].
• In the adult, annexin V was highly concentrated in epithelial cells lining the bile ducts, and along the bile canaliculi [9].
• Annexin V and terminal differentiation of growth plate chondrocytes [11].
• Here we used targeted gene disruption to generate B-lymphocytes lacking annexin 5 (Anx5) expression and show that this results in reduced susceptibility to a range of apoptotic stimuli [12].
• In a previous study, we have identified endonexin II (E-II) on human liver plasma membranes as a specific, Ca(2+)-dependent, small hepatitis B surface antigen (HBsAg)-binding protein [1].

Associations of ANXA5 with chemical compounds

• Amino-terminal sequence analysis of the peptides generated by site-specific cleavage of the 33- and the 36-kDa MV annexins at tryptophan residues indicate that the 33 kDa is highly homologous to anchorin CII, a protein known to bind type II collagen, while the 36-kDa protein shares close homology with endonexin II, a tyrosine kinase substrate [13].
• Chelating cytosolic Ca(2+) with BAPTA-AM, interfering with annexin Ca(2+) channel activities using K-201, a specific annexin Ca(2+) channel blocker, or suppression of annexin V expression using siRNA inhibited these events [11].
• Overexpression of annexin V in embryonic chicken growth plate chondrocytes resulted in an increase of cytoplasmic Ca(2+) concentration, [Ca(2+)](i) similar to [Ca(2+)](i) increase in RA-treated cultures [11].
• When MVs are fused with planar phospholipid bilayers, a multiconductance Ca2+ channel is formed, with activity essentially identical to that observed when annexin V is delivered to the bilayer with phosphatidylserine liposomes [14].
• In addition, a significant fraction of annexin V associated with phosphatidylserine-rich liposomes was not extractable by EDTA treatment but required a detergent, indicating that annexin V inserts into bilayers of these liposomes [15].

Other interactions of ANXA5

• K-201 inhibited upregulation of osteocalcin and runx2 gene expression, APase expression and activity, and mineralization in annexin V-overexpressing growth plate chondrocytes [11].
• Types II and X collagen only bound to liposomes in the presence of annexin V but not in the presence of annexin II or VI [16].

Analytical, diagnostic and therapeutic context of ANXA5

• Genomic Southern blotting confirmed that chick anx5 is present as a single-copy gene [10].
• In immunofluorescence studies of isolated chondrocytes we observed a dense, punctate distribution of anchorin CII on the cell surface when chondrocytes were enclosed by a pericellular type II collagen matrix [17].
• The presence of anchorin CII protein during stages 11 to 20 was confirmed by Western blotting [2].
• Cross-reactivity of anti-E-II antibodies to HBsAg epitopes was excluded, since anti-HBs and anti-E-II activities can be separated by E-II affinity chromatography [1].
• The conformational rearrangements that take place after calcium binding in chicken annexin A5 and a mutant lacking residues 3-10 were analyzed, in parallel with human annexin A5, by circular dichroism (CD), infrared spectroscopy (IR), and differential scanning calorimetry [18].

References