A C2 domain is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 structural domain involved in targeting proteins to cell membranes. It is a beta-sandwich composed of 8 β-strand

Beta sheet

The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

s that co-ordinates two or three calcium

Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 ions, which bind in a cavity 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

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 domains; for example, the C2 domain in PTEN

PTEN

PTEN may mean:* Patterson-UTI Energy, Inc., which trades on the NASDAQ stock market under the symbol 'PTEN'* Prime Time Entertainment Network* PTEN , a human tumour suppressor gene on chromosome 10...

, brings the phosphatase

Phosphatase

A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...

 domain into contact with the membrane where it can dephosphorylate its substrate, phosphatidylinositol (3,4,5)-trisphosphate (PIP₃)

Phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol -triphosphate , abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases phosphorylation on phosphatidylinositol -bisphosphate .-Discovery:...

, without removing it from the membrane - which would be energetically very costly. In addition to this, phosphatidylinositol 3-kinase

Phosphoinositide 3-kinase

Phosphatidylinositol 3-kinases are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In response to lipopolysaccharide, PI3K phosphorylates p65, inducing...

 (PI3-kinase), an enzyme that phosphorylates

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 phosphoinositides on the 3-hydroxyl group of the inositol

Inositol

Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-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

Clostridium perfringens alpha toxin

Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity....

, where they are used to bring the catalytic phospholipase domain into contact with the plasma membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

, 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 to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding and in membrane targeting processes such as subcellular localisation.

3D structure

3D structure of C2 domains has been reported, the domain forms an eight-stranded beta sandwich constructed around a conserved 4-stranded motif, designated a C2 key. 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

BAIAP3

BAI1-associated protein 3 is a protein that in humans is encoded by the BAIAP3 gene.-Interactions:BAIAP3 has been shown to interact with Brain-specific angiogenesis inhibitor 1.-Further reading:...

; BCR

BCR gene

The BCR gene is one of the two genes in the bcr-abl complex, which is associated with the Philadelphia chromosome.-Pathology:...

; C2CD2; C2CD3; C8orfK23; CADPS

CADPS

Calcium-dependent secretion activator 1 is a protein that in humans is encoded by the CADPS gene.-Further reading:...

; CADPS2

CADPS2

Calcium-dependent secretion activator 2 is a protein that in humans is encoded by the CADPS2 gene.- Function :This gene encodes a member of the calcium-dependent activator of secretion protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core...

;
CAPN5

CAPN5

Calpain-5 is a protein that in humans is encoded by the CAPN5 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...

; CAPN6; CC2D1A

CC2D1A

Coiled-coil and C2 domain-containing protein 1A is a protein that in humans is encoded by the CC2D1A gene.-Further reading:...

; CC2D1B; CPNE1

CPNE1

Copine-1 is a protein that in humans is encoded by the CPNE1 gene.-Further reading:...

; CPNE2; CPNE3; CPNE4

CPNE4

Copine-4 is a protein that in humans is encoded by the CPNE4 gene.-Further reading:...

;
CPNE5; CPNE6

CPNE6

Copine-6 is a protein that in humans is encoded by the CPNE6 gene.-Further reading:...

; CPNE7; CPNE8

CPNE8

Copine-8 is a protein that in humans is encoded by the CPNE8 gene.-Further reading:...

; CPNE9; DAB2IP

DAB2IP

Disabled homolog 2-interacting protein is a protein that in humans is encoded by the DAB2IP gene.-Further reading:...

; DOC2A

DOC2A

Double C2-like domain-containing protein alpha is a protein that in humans is encoded by the DOC2A gene.-Further reading:...

; DOC2B

DOC2B

Double C2-like domain-containing protein beta is a protein that in humans is encoded by the DOC2B gene.-Further reading:...

;
DYSF; ESYT1; ESYT3; FAM62A

FAM62A

Extended synaptotagmin-1 is a protein that in humans is encoded by the ESYT1 gene.-Further reading:...

; FAM62B

FAM62B

Extended synaptotagmin-2 is a protein that in humans is encoded by the ESYT2 gene.-Further reading:...

; FAM62C; FER1L3

FER1L3

Myoferlin is a protein that in humans is encoded by the MYOF gene.-Further reading:...

; FER1L5;
HECW1; HECW2; ITCH

Itch

Itch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...

; ITSN1

ITSN1

Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.-Interactions:ITSN1 has been shown to interact with SNAP-25, SOS1, SCAMP1 and CDC42.-Further reading:...

; ITSN2

ITSN2

Intersectin-2 is a protein that in humans is encoded by the ITSN2 gene.-Interactions:ITSN2 has been shown to interact with Wiskott-Aldrich syndrome protein.-Further reading:...

; KIAA0528; KIAA1228; KIAA1957;
LOC392742; MCTP1; MCTP2; MTAC2D1; NEDD4

NEDD4

E3 ubiquitin-protein ligase NEDD4 also known as neural precursor cell expressed developmentally down-regulated protein 4 is an enzyme that in humans is encoded by the NEDD4 gene....

; NEDD4L

NEDD4L

E3 ubiquitin-protein ligase NEDD4-like is an enzyme that in humans is encoded by the NEDD4L gene.-Further reading:...

; NEDL1; OTOF

OTOF

Otoferlin is a protein that in humans is encoded by the OTOF gene.-External links:* -Further reading:...

;
PCLO

PCLO

Protein piccolo is a protein that in humans is encoded by the PCLO gene.-Further reading:...

; PIK3C2A

PIK3C2A

Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the PIK3C2A gene.-Further reading:...

; PIK3C2B

PIK3C2B

Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the PIK3C2B gene.-Further reading:...

; PIK3C2G

PIK3C2G

Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing gamma polypeptide is an enzyme that in humans is encoded by the PIK3C2G gene.-Further reading:...

; PLA2G4A

PLA2G4A

Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the PLA2G4A gene.-Further reading:...

; PLA2G4B

PLA2G4B

Phospholipase A2, group IVB , also known as PLA2G4B, is a human gene.-Further reading:...

; PLA2G4D; PLA2G4E;
PLA2G4F; PLCB1

PLCB1

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-1 is an enzyme that in humans is encoded by the PLCB1 gene.-Further reading:...

; PLCB2

PLCB2

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2 is an enzyme that in humans is encoded by the PLCB2 gene. The gene codes for the enzyme phospholipase C β2. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...

; PLCB3

PLCB3

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene. The gene codes for the enzyme phospholipase C β3. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...

; PLCB4

PLCB4

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-4 is an enzyme that in humans is encoded by the PLCB4 gene.- Function :The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...

; PLCD1

PLCD1

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-1 is an enzyme that in humans is encoded by the PLCD1 gene.PLCd1 is essential to maintain homeostasis of the skin.-External links:*...

; PLCD3

PLCD3

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3 is an enzyme that in humans is encoded by the PLCD3 gene.A lot of plcd3 express to the brain.- Function :...

; PLCD4

PLCD4

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-4 is an enzyme that in humans is encoded by the PLCD4 gene....

;
PLCE1

PLCE1

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 is an enzyme that in humans is encoded by the PLCE1 gene.- Function :...

; PLCG1

PLCG1

Phospholipase C, gamma 1, also known as PLCG1, is a protein that in humans is encoded by the PLCG1 gene.-Function:The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate...

; PLCG2

PLCG2

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 is an enzyme that in humans is encoded by the PLCG2 gene.- Function :Enzymes of the phospholipase C family catalyze the hydrolysis of phospholipids to yield diacylglycerols and water-soluble phosphorylated derivatives of the lipid...

; PLCH1; PLCH2; PLCL1; PLCL2; PLCZ1;
PRF1; PRKCA; PRKCB1

PRKCB1

Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

; PRKCE

PRKCE

Protein kinase C epsilon type is an enzyme that in humans is encoded by the PRKCE gene.- Function :Protein kinase C is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol...

; PRKCG

PRKCG

Protein kinase C gamma type is an enzyme that in humans is encoded by the PRKCG gene.-External Links:* -Further reading:...

; PRKCH

PRKCH

Protein kinase C eta type is an enzyme that in humans is encoded by the PRKCH gene.-Further reading:...

; RAB11FIP1

RAB11FIP1

Rab11 family-interacting protein 1 also known as Rab-coupling protein is a protein that in humans is encoded by the RAB11FIP1 gene.- Function :...

; RAB11FIP2

RAB11FIP2

Rab11 family-interacting protein 2 is a protein that in humans is encoded by the RAB11FIP2 gene.-Interactions:RAB11FIP2 has been shown to interact with MYO5B, RAB11A and RAB25.-Further reading:...

;
RAB11FIP5

RAB11FIP5

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.-Interactions:RAB11FIP5 has been shown to interact with RAB11A and RAB25.-Further reading:...

; RASA1; RASA2; RASA3

RASA3

Ras GTPase-activating protein 3 is an enzyme that in humans is encoded by the RASA3 gene.-Further reading:...

; RASA4

RASA4

Ras GTPase-activating protein 4 is an enzyme that in humans is encoded by the RASA4 gene.-Further reading:...

; RASAL1; RASAL2

RASAL2

Ras GTPase-activating protein nGAP is an enzyme that in humans is encoded by the RASAL2 gene.-Further reading:...

; RGS3

RGS3

Regulator of G-protein signaling 3 is a protein that in humans is encoded by the RGS3 gene.-Further reading:...

;
RIMS1

RIMS1

Regulating synaptic membrane exocytosis protein 1 is a protein that in humans is encoded by the RIMS1 gene.-Interactions:RIMS1 has been shown to interact with UNC13B, RAB3A, ERC2 and YWHAH.-Further reading:...

; RIMS2

RIMS2

Regulating synaptic membrane exocytosis protein 2 is a protein that in humans is encoded by the RIMS2 gene.-Interactions:RIMS2 has been shown to interact with YWHAH and RAPGEF4.-Further reading:...

; RIMS3; RIMS4; RPGRIP1

RPGRIP1

X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is an enzyme that in humans is encoded by the RPGRIP1 gene.-Interactions:RPGRIP1 has been shown to interact with Retinitis pigmentosa GTPase regulator.-Further reading:...

; RPGRIP1L

RPGRIP1L

RPGRIP1L is a human gene.-Function:The protein encoded by this gene is localized to primary cilia and centrosomes in ciliated human epithelial kidney cells...

; RPH3A

RPH3A

Rabphilin-3A is a protein that in humans is encoded by the RPH3A gene.It contains two C2 domains and binds calcium ions at low micromolar concentration...

; SGA72M;
SMURF1

SMURF1

E3 ubiquitin-protein ligase SMURF1 is an enzyme that in humans is encoded by the SMURF1 gene.-Interactions:SMURF1 has been shown to interact with ARHGEF9, PLEKHO1 and SMURF2.-Further reading:...

; SMURF2

SMURF2

E3 ubiquitin-protein ligase SMURF2 is an enzyme that in humans is encoded by the SMURF2 gene.-Interactions:SMURF2 has been shown to interact with Mothers against decapentaplegic homolog 7, SCYE1, SMURF1, Mothers against decapentaplegic homolog 3, Ubiquitin C, Mothers against decapentaplegic homolog...

; SYNGAP1

SYNGAP1

Synaptic Ras GTPase activating protein 1 homolog , also known as SYNGAP1, is a protein which in humans is encoded by the SYNGAP1 gene. SYNGAP1 is a ras GTPase-activating protein that is critical for cognition and synapse function. Mutations in humans cause mental retardation.- Function :Unc51.1 and...

; SYT1

SYT1

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.SYT1 is the master switch responsible for allowing the human brain to release neurotransmitters...

; SYT10; SYT11

SYT11

Synaptotagmin-11 is a protein that in humans is encoded by the SYT11 gene.-Interactions:SYT11 has been shown to interact with Parkin .-Further reading:...

; SYT12; SYT13

SYT13

Synaptotagmin-13 is a protein that in humans is encoded by the SYT13 gene.-Further reading:...

;
SYT14; SYT14L; SYT15; SYT16; SYT17; SYT2

SYT2

Synaptotagmin-2 is a protein that in humans is encoded by the SYT2 gene.-Further reading:...

; SYT3

SYT3

Synaptotagmin-3 is a protein that in humans is encoded by the SYT3 gene.-Further reading:...

; SYT4

SYT4

Synaptotagmin-4 is a protein that in humans is encoded by the SYT4 gene.-Further reading:...

;
SYT5

SYT5

Synaptotagmin-5 is a protein that in humans is encoded by the SYT5 gene.-Further reading:...

; SYT6

SYT6

Synaptotagmin-6 is a protein that in humans is encoded by the SYT6 gene.-Further reading:...

; SYT7

SYT7

Synaptotagmin-7 is a protein that in humans is encoded by the SYT7 gene.-Further reading:...

; SYT8; SYT9

SYT9

Synaptotagmin-9 is a protein that in humans is encoded by the SYT9 gene.-Interactions:SYT9 has been shown to interact with SYNCRIP, TUBB and TRPV1.-Further reading:...

; SYTL1

SYTL1

Synaptotagmin-like protein 1 is a protein that in humans is encoded by the SYTL1 gene.-Further reading:...

; SYTL2

SYTL2

Synaptotagmin-like 2, also known as SYTL2, is a human gene.-Further reading:...

; SYTL3;
SYTL4

SYTL4

Synaptotagmin-like protein 4 is a protein that in humans is encoded by the SYTL4 gene.-Further reading:...

; SYTL5; TOLLIP

TOLLIP

Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.-Function:It is an inhibitory adaptor protein within Toll-like receptors...

; UNC13A; UNC13B

UNC13B

Protein unc-13 homolog B is a protein that in humans is encoded by the UNC13B gene.-Interactions:UNC13B has been shown to interact with STX1B, STX1A, RIMS1, SPTBN2 and DOC2A.-Further reading:...

; UNC13C; UNC13D

UNC13D

Protein unc-13 homolog D, also known as munc13-4, is a protein that in humans is encoded by the UNC13D gene.- Function :Munc13-4 is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other...

; WWC2;
WWP1

WWP1

NEDD4-like E3 ubiquitin-protein ligase WWP1 is an enzyme that in humans is encoded by the WWP1 gene.-Interactions:WWP1 has been shown to interact with KLF2, Reticulon 4 and CPSF6.-Further reading:...

; WWP2

WWP2

NEDD4-like E3 ubiquitin-protein ligase WWP2 also known as atrophin-1-interacting protein 2 or WW domain-containing protein 2 is an enzyme that in humans is encoded by the WWP2 gene.- Function :...

; sytdep;

External links

• Phosphoinositide 3-kinase C2 family in Pfam - Orientations of C2 domains in membranes (OPM)