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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,E1] 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.

Hofmann K.

May 2005 / Text revised and pattern removed.

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

C2, PS50004; C2 domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL, except for the 110 Kd catalytic subunit of PI3-kinase and a few divergent PKC isoforms Other sequence(s) detected in Swiss-Prot: 2.

• Domain architecture view of Swiss-Prot proteins matching PS50004 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50004 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50004 • Scan Swiss-Prot/TrEMBL entries against PS50004 • view ligand binding statistics

Matching PDB structures: 1A25 1BCI 1BYN 1CJY ... [ALL]

1	Authors	Azzi A., Boscoboinik D., Hensey C.
	Title	The protein kinase C family.
	Source	Eur. J. Biochem. 208:547-557(1992).
	PubMed ID	1396661

2	Authors	Stabel S.
	Source	Semin. Cancer Biol. 5:277-284(1994).

3	Authors	Brose N., Hofmann K., Hata Y., Suedhof T.C.
	Title	Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.
	Source	J. Biol. Chem. 270:25273-25280(1995).
	PubMed ID	7559667

4	Authors	Sossin W.S., Schwartz J.H.
	Title	Ca(2+)-independent protein kinase Cs contain an amino-terminal domain similar to the C2 consensus sequence.
	Source	Trends Biochem. Sci. 18:207-208(1993).
	PubMed ID	8346555

5	Authors	Davletov B.A., Suedhof T.C.
	Title	A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.
	Source	J. Biol. Chem. 268:26386-26390(1993).
	PubMed ID	8253763

6	Authors	Fukuda M., Aruga J., Niinobe M., Aimoto S., Mikoshiba K.
	Title	Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II.
	Source	J. Biol. Chem. 269:29206-29211(1994).
	PubMed ID	7961887

7	Authors	Sutton R.B., Davletov B.A., Berghuis A.M., Suedhof T.C., Sprang S.R.
	Title	Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
	Source	Cell 80:929-938(1995).
	PubMed ID	7697723

E1
Source	http://www.isrec.isb-sib.ch/profile/davos95/poster.html

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