PROSITE documentation PDOC00380
C2 domain profile


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 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 [4].
  • 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 [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 β sandwich.

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

Expert(s) to contact by email:

Hofmann K.

Last update:

December 2019 / Profile revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

C2, PS50004; C2 domain profile  (MATRIX)


1AuthorsAzzi A. Boscoboinik D. Hensey C.
TitleThe protein kinase C family.
SourceEur. J. Biochem. 208:547-557(1992).
PubMed ID1396661

2AuthorsStabel S.
SourceSemin. Cancer Biol. 5:277-284(1994).

3AuthorsBrose N. Hofmann K. Hata Y. Suedhof T.C.
TitleMammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.
SourceJ. Biol. Chem. 270:25273-25280(1995).
PubMed ID7559667

4AuthorsSossin W.S. Schwartz J.H.
TitleCa(2+)-independent protein kinase Cs contain an amino-terminal domain similar to the C2 consensus sequence.
SourceTrends Biochem. Sci. 18:207-208(1993).
PubMed ID8346555

5AuthorsDavletov B.A. Suedhof T.C.
TitleA single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.
SourceJ. Biol. Chem. 268:26386-26390(1993).
PubMed ID8253763

6AuthorsFukuda M. Aruga J. Niinobe M. Aimoto S. Mikoshiba K.
TitleInositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II.
SourceJ. Biol. Chem. 269:29206-29211(1994).
PubMed ID7961887

7AuthorsSutton R.B. Davletov B.A. Berghuis A.M. Suedhof T.C. Sprang S.R.
TitleStructure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
SourceCell 80:929-938(1995).
PubMed ID7697723

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