Some isozymes of protein kinase C (PKC) [1,2] contain a domain, known as C2,
of about 116 amino-acid residues which is located between the two copies of
the C1 domain (that bind phorbol esters and diacylglycerol) (see <PDOC00379>)
and the protein kinase catalytic domain (see <PDOC00100>). Regions with
significant homology  to the C2-domain have been found in the following
PKC isoforms α, β and γ and Drosophila isoforms PKC1 and PKC2.
PKC isoforms delta, epsilon and eta, Caenorhabditis elegans kin-13 and
yeast PKC1 have a C2-like domain at the N-terminal extremity .
Yeast cAMP dependent protein kinase SCH9 contains a C2-like domain.
Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see
<PDOC50007>) isoforms β, γ and delta as well as several non-
mammalian PI-PLCs have a C2-like domain C-terminal of the catalytic domain.
Mammalian and plants phosphatidylinositol-3-kinase have a C2-like domain in
the central region of the 110 Kd catalytic subunit.
Yeast phosphatidylserine-decarboxylase 2 (gene PSD2) contains a C2 domain
in its central region.
Cytosolic phospholipase D from plants and cytosolic phospholipase A2 have a
C2-like domain at their N-terminus.
Synaptotagmins (p65). This is a family of related synaptic vesicle proteins
that bind acidic phospholipids and that may have a regulatory role in the
membrane interactions during trafficking of synaptic vesicles at the active
zone of the synapse. All isoforms of synaptotagmins have two copies of the
C2 domain in their C-terminal region.
Rabphilin-3A, a synaptic protein contains two C2 domains.
Caenorhabditis elegans protein unc-13 whose function is not known. Unc-13
has a C2 domain in its central part and a C2-like domain at the C-terminus.
rasGAP and the breakpoint cluster protein bcr have a C2-domain C-terminal
of a PH-domain.
Yeast protein BUD2 (or CLA2) has a C2-domain in the central region.
Yeast protein RSP5 and human protein NEDD-4, both proteins also contain WW
domains (see <PDOC50020>).
Perforin (see <PDOC00251>) has a C2 domain at the C-terminus. It is the
only extracellular protein known to contain a C2 domain.
Yeast hypothetical protein YML072C has a C2 domain.
Yeast hypothetical protein YNL087W has three C2 domains.
Caenorhabditis elegans hypothetical protein F37A4.7 has two C2 domains.
The C2 domain is thought to be involved in calcium-dependent phospholipid
binding . Since domains related to the C2 domain are also found in proteins
that do not bind calcium, other putative functions for the C2 domain like e.g.
binding to inositol-1,3,4,5-tetraphosphate have been suggested . The 3D
structure of the first C2 domain of synaptotagmin shows that the domain
forms an eight-stranded β sandwich.
The profile we developed for the C2 domain covers the total domain.
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