Annexins
243
N
C
C
C
C
C
C
C
N
N
N
N
N
N
YS
Y
Y
Y
YYYYYY
S
S
plO
plO
Endonexin
(Annexin IV)
Endonexin II
(Annexin V)
Lipocortin
(Annexin I)
Synexin
(Annexin VII)
Calpactin
(Annexin II)
68 K
Calelectrin
(Annexin VI)
Fig. 1
Schematic illustration of the primary
structures of six annexins. Each of the 4 (or 8)
homologous domains contains the 17–amino
acid ‘‘endonexin fold’’ sequence represented by a
sawtooth line (sequence: KGhGTDExxLIpILApR:
h, hydrophobic residue; p, polar residue; x,
variable residue). The unique N-terminal
structuresareontheleft(orrightinthecaseof
annexin VI); Y and S represent phosphorylation
sites in the tails of annexins I and II. The annexin
II tetramer is drawn showing the association of
the N-termini of the heavy chains with the
light-chain (p10) dimer. The
Y
s inside the loops
in the tail of synexin represent a pro-
β
-helix.
[Reproduced from Dedman and Smith (1990),
with permission.]
of blood coagulation, transducers of sig-
nals generated by tyrosine kinases at
the cell membrane, mediators of bone
formation and remodeling, mediators of
cell-matrix interactions, voltage-dependent
ion channels, actin bundling proteins, reg-
ulators of calcium release channels in
muscle, regulators of DNA polymerase
activity, and extracellular binding sites
for plasminogen. This diversity of hy-
potheses attests to the ubiquitous and
abundant nature of these proteins. In
most cases, the data supporting a role
for the annexins in these various pro-
cesses are derived from
in vitro
systems
involving calcium and lipid membranes,
and it has been difFcult to relate these
activities to true cellular functions. How-
ever, it seems likely that this family of
proteins has radiated to perform a vari-
ety of cellular functions, since so many
a
recoexp
res
sedins
ing
lece
l
l
sandthe
i
r
individual differences have been highly
conserved during evolution. In that sense,
the annexins may be similar to the other
major class of calcium-binding proteins,
the ‘‘E±-hand’’ family, which includes
calmodulin and troponin C, and are re-
sponsible for a variety of nonoverlapping
cellular phenomena.
