Covalent attachment of phosphate, as in the enzyme-catalyzed phosphorylation of serine
or tyrosine amino acid side chains in a protein.
The annexins are a family of structurally related, calcium-dependent, phospholipid-
binding proteins that have been postulated to mediate calcium-dependent activities at
membrane surfaces such as membrane fusion, lipid metabolism and reorganization,
and ion permeation. The basic annexin structure consists of 4 homologous 70–amino
acid repeats and a unique N-terminal domain. These repeats do not contain
sequences found in other intracellular calcium-binding proteins; therefore, the
annexins represent a novel class of calcium-binding proteins. The ‘‘core’’ domains
of all the annexins, composed of the four 70–amino acid repeats, are 40 to 60%
identical in sequence. One annexin family member (annexin VI) has been formed
as a result of gene duplication and consists of 8 of the 70–amino acid repeats.
Another type of duplication has occurred with annexin II (calpactin), in which two
36-kDa molecules, the ‘‘heavy chains,’’ each containing four repeats, bind to a dimer
of a 10-kDa protein, the ‘‘light chains,’’ to form a tetramer. In contrast to other
lipid-binding proteins such as protein kinase C, or phospholipase A2, the annexins
are unique in that most are bivalent. That is, they can attach to two membranes,
rather than just one, and as a consequence, draw them together.
Diversity and Functions
Members of the annexin family of pro-
teins, of which there are now 11 recognized
mammalian variants, have been indepen-
dently discovered in a number of contexts.
As a consequence, a variety of names
have been used for the different family
members, such as
synexins, chromobindins,
lipocortins, calcimedins, calphobindins
. However, a standard reference
nomenclature has been adopted involving
the term
followed by a Roman
numeral (Fig. 1). Representative annexins
have been isolated from animals, plants,
and the slime mold
ing to the universality of the functions
performed by annexins. Owing to the
bivalent activity of the annexins, one of
their postulated roles is the promotion
of membrane fusion in exocytosis. After
secretory vesicle membranes have been
aggregated by an annexin, they undergo
fusion if exposed to cis-unsaturated fatty
acids. In a cell, such fusogenic fatty acids
might be made available through activa-
tion of lipases. Alternatively, the annexins
might function in concert with other pro-
teins that promote membrane fusion and
remodeling after the membranes have
been brought into close apposition by the
annexin. In addition to a possible role
in exocytosis and membrane traf±cking,
some of the annexins have been suggested
to be mediators of the anti-inflammatory
effects of steroids, components of the
submembranous cytoskeleton, inhibitors
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