{PDOC00380}
{PS50004; C2}
{BEGIN}
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* C2 domain profile *
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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  [3]  to  the  C2-domain have been found in the following
proteins:

 - PKC isoforms alpha, beta and gamma 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 [4].
 - Yeast cAMP dependent protein kinase SCH9 contains a C2-like domain.
 - Mammalian   phosphatidylinositol-specific  phospholipase  C  (PI-PLC)  (see
   <PDOC50007>) isoforms  beta,  gamma  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 [5]. 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 [6]. The 3D
structure of  the  first  C2 domain of synaptotagmin [7] shows that the domain
forms an eight-stranded beta sandwich.

The profile we developed for the C2 domain covers the total domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Hofmann K.; kay.hofmann@memorec.com

-Last update: December 2019 / Profile revised.

[ 1] Azzi A., Boscoboinik D., Hensey C.
     "The protein kinase C family."
     Eur. J. Biochem. 208:547-557(1992).
     PubMed=1396661
[ 2] Stabel S.
     Semin. Cancer Biol. 5:277-284(1994).
[ 3] Brose N., Hofmann K., Hata Y., Suedhof T.C.
     "Mammalian homologues of Caenorhabditis elegans unc-13 gene define
     novel family of C2-domain proteins."
     J. Biol. Chem. 270:25273-25280(1995).
     PubMed=7559667
[ 4] Sossin W.S., Schwartz J.H.
     "Ca(2+)-independent protein kinase Cs contain an amino-terminal domain
     similar to the C2 consensus sequence."
     Trends Biochem. Sci. 18:207-208(1993).
     PubMed=8346555
[ 5] Davletov B.A., Suedhof T.C.
     "A single C2 domain from synaptotagmin I is sufficient for high
     affinity Ca2+/phospholipid binding."
     J. Biol. Chem. 268:26386-26390(1993).
     PubMed=8253763
[ 6] Fukuda M., Aruga J., Niinobe M., Aimoto S., Mikoshiba K.
     "Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of
     IP4BP/synaptotagmin II."
     J. Biol. Chem. 269:29206-29211(1994).
     PubMed=7961887
[ 7] Sutton R.B., Davletov B.A., Berghuis A.M., Suedhof T.C., Sprang S.R.
     "Structure of the first C2 domain of synaptotagmin I: a novel
     Ca2+/phospholipid-binding fold."
     Cell 80:929-938(1995).
     PubMed=7697723

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