C2 domain: Difference between revisions
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==External links== |
==External links== |
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*[http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC00380 C2 domain] in [[PROSITE]] |
*[http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC00380 C2 domain] in [[PROSITE]] |
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*[http:// |
*[http://pfam.sanger.ac.uk/family?entry=PF00168 C2 domain family in Pfam] |
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*[http:// |
*[http://pfam.sanger.ac.uk/family?entry=PF00792 Phosphoinositide 3-kinase C2 family in Pfam] |
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* {{UMichOPM|families|superfamily|47}} - Orientations of C2 domains in membranes (OPM) |
* {{UMichOPM|families|superfamily|47}} - Orientations of C2 domains in membranes (OPM) |
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Revision as of 15:30, 13 May 2008
C2 domain | |||||||||||
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Identifiers | |||||||||||
Symbol | C2 | ||||||||||
Pfam | PF00168 | ||||||||||
InterPro | IPR000008 | ||||||||||
SMART | C2 | ||||||||||
PROSITE | PDOC00380 | ||||||||||
SCOP2 | 1qas / SCOPe / SUPFAM | ||||||||||
OPM superfamily | 47 | ||||||||||
OPM protein | 1ugk | ||||||||||
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A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is composed of 8 β-sheets, forming a beta-sandwich motif, and co-ordinates 2 or 3 calcium ions, which bind in an indentation formed by the first and final loops of the domain, on the membrane binding face.
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, 3,4,5 tetraphospho-inositol, 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.
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.
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.
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;
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. PMID 7559667.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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. PMID 7697723.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)
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)