Summary: C2 domain
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C2 domain Edit Wikipedia article
C2 domain is a Ca2+-dependent membrane targeting module found in many cellular proteins involved in signal transduction or membrane trafficking.
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) and the protein kinase catalytic domain. Regions with significant homology to the C2-domain have been found in many proteins [1]. The C2 domain is involved in calcium-dependent phospholipid binding.
The 3D structure of the C2 forms an eight stranded beta sandwich. Calcium binds in a cup-shaped depression formed by the N- and C-terminal loops of the beta-sandwich.
A separate family is C2 domains of phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring (e.g. 1e8w PDB entry).
External links
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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Literature references
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Ponting CP, Parker PJ; , Protein Sci 1996;5:162-166.: Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin. PUBMED:8771209 EPMC:8771209
Internal database links
SCOOP: | C2-C2_1 CEP76-C2 Haspin_kinase MUN NT-C2 Peptidase_M50 PI3K_C2 |
Similarity to PfamA using HHSearch: | PI3K_C2 |
External database links
HOMSTRAD: | C2 |
PRINTS: | PR00360 |
PROSITE: | PDOC00380 |
SCOP: | 1qas |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000008
The C2 domain is a Ca 2+ -dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. 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 and the protein kinase catalytic domain [ PUBMED:22453964 ]. Regions with significant homology [ PUBMED:7559667 ] to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding [ PUBMED:8253763 ] and in membrane targetting processes such as subcellular localisation.
The 3D structure of the C2 domain of synaptotagmin has been reported [ PUBMED:7697723 ], the domain forms an eight-stranded beta sandwich constructed around a conserved 4-stranded motif, designated a C2 key [ PUBMED:7697723 ]. 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.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan C2 (CL0154), which has the following description:
This superfamily includes C2 domains and C2-like domains.
The clan contains the following 18 members:
Aida_C2 Anillin B9-C2 C2 C2-C2_1 CC2D2AN-C2 CEP76-C2 DOCK-C2 IcmF_C MNNL NT-C2 PI3K_C2 PTEN_C2 pYEATS RPGR1_C SPATA6 Spond_N YEATSAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (258) |
Full (183893) |
Representative proteomes | UniProt (285633) |
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RP15 (24537) |
RP35 (62416) |
RP55 (138140) |
RP75 (189297) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (258) |
Full (183893) |
Representative proteomes | UniProt (285633) |
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RP15 (24537) |
RP35 (62416) |
RP55 (138140) |
RP75 (189297) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
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Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Swissprot_feature_table |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Sonnhammer ELL |
Number in seed: | 258 |
Number in full: | 183893 |
Average length of the domain: | 106.4 aa |
Average identity of full alignment: | 19 % |
Average coverage of the sequence by the domain: | 19.67 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 103 | ||||||||||||
Family (HMM) version: | 33 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the C2 domain has been found. There are 339 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.