A C2 domain is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
structural domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of se ...
involved in targeting proteins to
cell membranes. The typical version (PKC-C2) has a
beta-sandwich composed of 8
β-strands that co-ordinates two or three
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face. Many other C2 domain families don't have calcium binding activity.
Coupling with other domains
C2 domains are frequently found coupled to
enzymatic domains; for example, the C2 domain in
PTEN, brings the
phosphatase
In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. Ph ...
domain into contact with the plasma 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. PTEN consists of two domains, a
protein tyrosine phosphatase domain and a C2 domain. This domain pair constitutes a superdomain, a heritable unit that is found in various proteins in fungi, plants and animals. In addition,
phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that
phosphorylates phosphoinositides
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
on the 3-hydroxyl group of the
inositol ring, also uses a C2 domain to bind to the membrane (e.g. 1e8w PDB entry).
Evolution
The C2 domain is currently only known from eukaryotes and the prokaryote ''
Clostridium perfringens
''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present in nature an ...
'' where it is part of the
alpha-toxin. Over 17 distinct clades of C2 domains have been identified.
Most C2 families can be traced back to
basal
Basal or basilar is a term meaning ''base'', ''bottom'', or ''minimum''.
Science
* Basal (anatomy), an anatomical term of location for features associated with the base of an organism or structure
* Basal (medicine), a minimal level that is nec ...
eukaryotic species indicating an early diversification before the last eukaryotic common ancestor (LECA). Only the PKC-C2 domain family contains conserved calcium-binding residues, suggesting the typical calcium-dependent membrane interaction is a derived feature limited in PKC-C2 domains.
Calcium and 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) (se
PDOC00379 and the protein kinase catalytic domain (se
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. Although most C2 domains interact with the membrane (phospholipids) in a Ca
2+-dependent manner, some C2 domains can interact with the membrane without binding to Ca
2+. Similarly, C2 domains have been evolved to have different specificities for lipids. Many C2 domains such as
synaptotagmin C2A, bind to anionic phospholipids (PS or PIP2 containing phospholipids). However, other C2 domains such as cPLA2-α C2 domain bind to zwitterionic lipids (e.g. PC). This diversity and selectivity in Ca
2+ and lipid binding suggest that C2 domains are evolved to have different functions.
3D structure
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 Ca
2+-binding loops are located at the end of an 8 stranded antiparallel beta sandwich.
Human proteins containing C2 domain
ABR
Abr or ABR may refer to:
Technology
* Available Bit Rate, a service used in ATM networks
* Average bitrate, the average amount of data transferred per second
* Area border router, in the Open Shortest Path First protocol
* Adaptive bit rate, a ...
;
BAIAP3;
BCR;
C2CD2;
C2CD3;
CADPS;
CADPS2;
CAPN5;
CAPN6;
CC2D1A;
CC2D1B;
CPNE1
Copine-1 is a protein that in humans is encoded by the ''CPNE1'' gene.
Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein ...
;
CPNE2
The Council of Pakistan Newspaper Editors (CPNE) has worked since its foundation in 1957 as the combined body of newspaper editors in Pakistan ;
CPNE3;
CPNE4;
CPNE5;
CPNE6
Copine-6 is a protein that in humans is encoded by the ''CPNE6'' gene.
This gene encodes a brain-specific member of the copine family, which is composed of calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As a ...
;
CPNE7;
CPNE8
Copine-8 is a protein that in humans is encoded by the ''CPNE8'' gene.
Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a ...
;
CPNE9;
DAB2IP;
DOC2A;
DOC2B;
DYSF
Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the ''DYSF'' gene.
Dysferlin is linked with skeletal muscle repair. A defect in the DYSF gene, located on chromosome 2p12-14, results in sev ...
;
ESYT1
Extended synaptotagmin-1 is a protein in humans that is encoded by the ''ESYT1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ' ...
;
ESYT3;
FAM62A;
FAM62B
Extended synaptotagmin-2 is a protein that in humans is encoded by the ''ESYT2'' gene.
References
Further reading
*
*
*
*
*
*
*
*
*
{{gene-7-stub ...
;
FAM62C;
FER1L3;
FER1L5;
HECW1
HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 is a protein that in humans is encoded by the HECW1 gene. In human it has 1606 amino acids (179.5 kDa) and isoelectric point
The isoelectric point (pI, pH(I), IEP), is the pH at whic ...
;
HECW2;
ITCH;
ITSN1;
ITSN2;
MCTP1;
MCTP2
Management Component Transport Protocol (MCTP) is a protocol designed by the Distributed Management Task Force (DMTF) to support communications between different intelligent hardware components that make up a platform management subsystem, provi ...
;
MTAC2D1;
NEDD4;
NEDD4L;
NEDL1;
OTOF
Otoferlin is a protein that in humans is encoded by the ''OTOF'' gene.
Function
Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has three C2 domains, a single ...
;
PCLO;
PIK3C2A;
PIK3C2B
Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the ''PIK3C2B'' gene.
Function
The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. P ...
;
PIK3C2G;
PLA2G4A;
PLA2G4B;
PLA2G4D;
PLA2G4E;
PLA2G4F;
PLCB1;
PLCB2;
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 an ...
;
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 ...
;
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.
See also
Phospholipase C
Phospholipase C (PLC) is a class of ...
;
PLCD3
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3 is an enzyme that in humans is encoded by the ''PLCD3'' gene.
Function
This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidyl ...
;
PLCD4
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-4 is an enzyme that in humans is encoded by the ''PLCD4'' gene.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
EC 3.1.4
EF-hand-containing proteins
{{ge ...
;
PLCE1;
PLCG1;
PLCG2;
PLCH1;
PLCH2 PLCH may stand for:
* Plch, a municipality in the Czech Republic
* The Public Library of Cincinnati and Hamilton County, a public library system in Cincinnati, Ohio, United States
* Pulmonary Langerhans' cell histiocytosis, a type of interstitial ...
;
PLCL1;
PLCL2 PLCL may refer to:
* Park Lane College Leeds, a former British further education college, now part of Leeds City College
* '' Parker Lewis Can't Lose'', a 1990s television series
{{disambiguation ...
;
PLCZ1;
PRF1
Perforin-1 is a protein that in humans is encoded by the ''PRF1'' gene and the ''Prf1'' gene in mice.
Function
Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cel ...
;
PRKCA;
PRKCB1;
PRKCE;
PRKCG
Protein kinase C gamma type is an enzyme that in humans is encoded by the ''PRKCG'' gene.
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. ...
;
PRKCH;
RAB11FIP1;
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
Ras-related protein Rab-25 is a protein that in humans is e ...
;
RAB11FIP5;
RASA1;
RASA2
Rasa may refer to:
Indian culture
* Rasa (aesthetics), a concept in the Indian performing arts
* Rasa (theology), a concept of nectar or emotional rapture related to Krishna devotion
* Rasā, a mythical river mentioned in the Rigveda
* Rasa li ...
;
RASA3;
RASA4
Ras GTPase-activating protein 4 is an enzyme that in humans is encoded by the ''RASA4'' gene.
This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein kinase pathway in respons ...
;
RASAL1;
RASAL2
Ras GTPase-activating protein nGAP is an enzyme that in humans is encoded by the ''RASAL2'' gene.
This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs funct ...
;
RGS3
Regulator of G-protein signaling 3 is a protein that in humans is encoded by the ''RGS3'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generat ...
;
RIMS1;
RIMS2;
RIMS3;
RIMS4;
RPGRIP1
X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is a protein in the ciliary transition zone that in humans is encoded by the ''RPGRIP1'' gene. RPGRIP1 is a multi-domain protein containing a coiled-coil domain at the N-term ...
;
RPGRIP1L;
RPH3A;
SGA72M;
SMURF1;
SMURF2;
SYNGAP1;
SYT1;
SYT10
Synaptotagmin-1 is a protein that in humans is encoded by the ''SYT1'' gene.
Function
Synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as sensors for calcium ions (Ca2+) in the process of vesicular trafficking ...
;
SYT11;
SYT12
Synaptotagmin-1 is a protein that in humans is encoded by the ''SYT1'' gene.
Function
Synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as sensors for calcium ions (Ca2+) in the process of vesicular trafficki ...
;
SYT13
Synaptotagmin-13 is a protein that in humans is encoded by the ''SYT13'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
;
SYT14
Synaptotagmin XIV is a protein that in humans is encoded by the SYT14 gene.
Function
This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic tra ...
;
SYT14L;
SYT15;
SYT16;
SYT17;
SYT2
Synaptotagmin-2 is a protein that in humans is encoded by the ''SYT2'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
;
SYT3
Synaptotagmin-3 is a protein that in humans is encoded by the ''SYT3'' gene.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
{{protein-stub ...
;
SYT4
Synaptotagmin-4 is a protein that in humans is encoded by the ''SYT4'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
;
SYT5
Synaptotagmin-5 is a protein that in humans is encoded by the ''SYT5'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
;
SYT6
Synaptotagmin-6 is a protein that in humans is encoded by the ''SYT6'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...
;
SYT7;
SYT8;
SYT9;
SYTL1
Synaptotagmin-like protein 1 is a protein that in humans is encoded by the ''SYTL1'' gene.
Model organisms
Model organisms have been used in the study of SYTL1 function. A conditional knockout mouse line, called ''Sytl1tm1a(KOMP)Wtsi'' was ...
;
SYTL2
Synaptotagmin-like 2, also known as SYTL2, is a human gene.
Function
The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has ...
;
SYTL3;
SYTL4;
SYTL5;
TOLLIP;
UNC13A;
UNC13B;
UNC13C;
UNC13D;
WWC2
WW and C2 domain containing 2 (WWC2) is a protein that in humans is encoded by the ''WWC2'' gene (4q35.1). Though function of WWC2 remains unknown, it has been predicted that WWC2 may play a role in cancer.
Gene
Locus
The human gene WWC2 is f ...
;
WWP1;
WWP2;
PTEN
References
External links
Phosphoinositide 3-kinase C2 family in Pfam* - Orientations of C2 domains in membranes (OPM)
{{Protein domains
Peripheral membrane proteins
Protein domains