C2 domain Information & C2 domain Links at HealthHaven.com

C2 domain
	The C2-domain of C.absonum α-toxin (PDB 1OLP). β-strands are shown in yellow. Co-ordinated Calcium ions are in cyan
Identifiers
Symbol	C2
Pfam	PF00168
InterPro	IPR000008
SMART	C2
PROSITE	PDOC00380
SCOP	1qas
OPM family	47
OPM protein	1ugk
Available PDB structures:
1a25B:173-260 1dsyA:173-260 3rpbA:557-645 1rh8A:4654-4752 1dqvA:314-400 1bynA:158-244 1ugkA:170-258 1uovA:289-377 1k5wA:289-377 1tjxA:289-377 1uowA:289-377 1tjmA:289-377 1w15A:304-392 1w16A:304-392 2b3rA:1574-1662 1v27A:822-913 2bwqA:760-851 1bci :20-106 1cjyA:20-106 1rlw :20-106 1wfjA:6-87 1djyA:631-720 1djhB:631-720 1djgB:631-720 1qatB:631-720 1djiB:631-720 2isdB:631-720 1djxA:631-720 1qasB:631-720 1djzB:631-720 1djwB:631-720 1gmiA:8-99 1wfmA:189-259

A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face.

[edit] Coupling with other domains

C2 domains are frequently found coupled to enzymatic domains; for example, the C2 domain in PTEN, brings the phosphatase domain into contact with the membrane where it can dephosphorylate its substrate, phosphatidylinositol (3,4,5)-trisphosphate (PIP₃), without removing it from the membrane - which would be energetically very costly. In addition to this, phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring, also uses a C2 domain to bind to the membrane (e.g. 1e8w PDB entry).

C2 domains are also found in clostridial alpha toxins, where they are used to bring the catalytic phospholipase domain into contact with the plasma membrane, conferring the toxic activity on the protein. These are the only known examples of C2 domains in prokaryotes.

[edit] Lipid selectivity

C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of the C1 domain in Protein Kinase C (that bind phorbol esters and diacylglycerol) (see PDOC00379) and the protein kinase catalytic domain (see PDOC00100). Regions with significant homology^[1] to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding^[2] and in membrane targeting processes such as subcellular localisation.

[edit] 3D structure

3D structure of C2 domains has been reported^[3], the domain forms an eight-stranded beta sandwich constructed around a conserved 4-stranded motif, designated a C2 key^[3]. Calcium binds in a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca²⁺-binding loops are located at the end of an 8 stranded antiparallel beta sandwich.

[edit] Human proteins containing C2 domain

ABR; BAIAP3; BCR; C2CD2; C2CD3; C8orfK23; CADPS; CADPS2; CAPN5; CAPN6; CC2D1A; CC2D1B; CPNE1; CPNE2; CPNE3; CPNE4; CPNE5; CPNE6; CPNE7; CPNE8; CPNE9; DAB2IP; DOC2A; DOC2B; DYSF; ESYT1; ESYT3; FAM62A; FAM62B; FAM62C; FER1L3; FER1L5; HECW1; HECW2; ITCH; ITSN1; ITSN2; KIAA0528; KIAA1228; KIAA1957; LOC392742; MCTP1; MCTP2; MTAC2D1; NEDD4; NEDD4L; NEDL1; OTOF; PCLO; PIK3C2A; PIK3C2B; PIK3C2G; PLA2G4A; PLA2G4B; PLA2G4D; PLA2G4E; PLA2G4F; PLCB1; PLCB2; PLCB3; PLCB4; PLCD1; PLCD3; PLCD4; PLCE1; PLCG1; PLCG2; PLCH1; PLCH2; PLCL1; PLCL2; PLCZ1; PRF1; PRKCA; PRKCB1; PRKCE; PRKCG; PRKCH; RAB11FIP1; RAB11FIP2; RAB11FIP5; RASA1; RASA2; RASA3; RASA4; RASAL1; RASAL2; RGS3; RIMS1; RIMS2; RIMS3; RIMS4; RPGRIP1; RPGRIP1L; RPH3A; SGA72M; SMURF1; SMURF2; SYNGAP1; SYT1; SYT10; SYT11; SYT12; SYT13; SYT14; SYT14L; SYT15; SYT16; SYT17; SYT2; SYT3; SYT4; SYT5; SYT6; SYT7; SYT8; SYT9; SYTL1; SYTL2; SYTL3; SYTL4; SYTL5; TOLLIP; UNC13A; UNC13B; UNC13C; UNC13D; WWC2; WWP1; WWP2; sytdep;

[edit] References

^ Hata Y, Hofmann K, Sudhof TC, Brose N (1995). "Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins". J. Biol. Chem. 270 (42): 25273–25280. doi:10.1074/jbc.270.42.25273. PMID 7559667.
^ Davletov BA, Sudhof TC (1993). "A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding". J. Biol. Chem. 268 (35): 26386–26390. PMID 8253763.
^ ^a ^b Sutton RB, Davletov BA, Berghuis AM, Sprang SR, Sudhof TC (1995). "Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold". Cell 80 (6): 929–938. doi:10.1016/0092-8674(95)90296-1. PMID 7697723.

[edit] External links

C2 domain in PROSITE
C2 domain family in Pfam
Phosphoinositide 3-kinase C2 family in Pfam
UMich Orientation of Proteins in Membranes families/superfamily-47 - Orientations of C2 domains in membranes (OPM)

[PUB00002925-0] Hata Y, Hofmann K, Sudhof TC, Brose N (1995). "Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins". J. Biol. Chem. 270 (42): 25273–25280. doi:10.1074/jbc.270.42.25273. PMID 7559667.

[PUB00002815-1] Davletov BA, Sudhof TC (1993). "A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding". J. Biol. Chem. 268 (35): 26386–26390. PMID 8253763.

[PUB00000918-2] Sutton RB, Davletov BA, Berghuis AM, Sprang SR, Sudhof TC (1995). "Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold". Cell 80 (6): 929–938. doi:10.1016/0092-8674(95)90296-1. PMID 7697723.

[1]

[2]

[3]