Annexins [1,2,3,4,5,6,7,8] are a group of calcium-binding proteins that associate
reversibly with membranes. They bind to phospholipid bilayers in the
presence of micromolar free calcium concentration. The binding is specific
for calcium and for acidic phospholipids. Annexins have been claimed to be
involved in cytoskeletal interactions, phospholipase inhibition, intracellular
signaling, anticoagulation, and membrane fusion. Annexins are widely
distributed among eukaryotes but largely absent in prokaryotes and yeast. They
are classified according to the evolutionary divisions of the eukaryotes into
five families: A (ANXA, vertebrates, including humans), B (ANXB,
invertebrates), C (ANXC, fungi), D (ANXD, true plants), E (ANXE, protists).
Each of these proteins consist of a unique N-terminal domain followed by four
or eight copies (in annexin A6) of a conserved segment of approximately 70
residues. The tertiary structure of annexins is evolutionary conserved; a
single molecule resembles a slightly curved disk with the calcium and
phospholipid-binding sites located on the more convex surface and the more
concave surface facing the cytoplasm. Each single annexin repeat (sometimes
known as an 'endonexin fold') is comprised of five α-helices(A–E) (see
<PDB:1AVR>). Four of them (A, B, D and E) are arranged parallel and form a
tightly packed helix-loop-helix bundle. In contrast, helix C is almost
perpendicular and covers the remaining four on the surface. Each of the
repeats has the potential to have a type II Ca(2+)-binding bipartite motif,
located on two different α-helices (GxGT-(38-40 residues)-D/E), but
typically some of them are non-functional. The core of the helix bundle is
composed largely of hydrophobic residues, while hydrophilic residues are
exposed on the surface of the protein and between the repeats. The N-terminal
domain of variable length, amino acid composition, and determinants of
hydrophobicity plays an important role in mediating the interaction of
annexins with other intracellular protein partners, such as those of the S100
family cytoplasmic proteins [7,8,9].
The proteins known to belong to the annexin family are listed below:
- Annexin I (Lipocortin 1) (Calpactin 2) (p35) (Chromobindin 9).
- Annexin II (Lipocortin 2) (Calpactin 1) (Protein I) (p36) (Chromobindin 8).
- Annexin III (Lipocortin 3) (PAP-III).
- Annexin IV (Lipocortin 4) (Endonexin I) (Protein II) (Chromobindin 4).
- Annexin V (Lipocortin 5) (Endonexin 2) (VAC-α) (Anchorin CII) (PAP-I).
- Annexin VI (Lipocortin 6) (Protein III) (Chromobindin 20) (p68) (p70). This
is the only known annexin that contains 8 (instead of 4) repeats.
- Annexin VII (Synexin).
- Annexin VIII (Vascular anticoagulant-β) (VAC-β).
- Annexin IX from Drosophila.
- Annexin X from Drosophila.
- Annexin XI (Calcyclin-associated annexin) (CAP-50).
- Annexin XII from Hydra vulgaris.
- Annexin XIII (Intestine-specific annexin) (ISA).
- α-Giardins from Giardia intestinalis, primitive homologues of annexins
The signature pattern for this domain spans positions 9 to 61 of the repeat
and includes the only perfectly conserved residue (an arginine in position
22). We also developed a profile which covers the entire annexin repeat.
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