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339  structures 1595  species 0  interactions 183893  sequences 2604  architectures

Family: C2 (PF00168)

Summary: C2 domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "C2 domain". More...

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

C2 domain Provide feedback

No Pfam abstract.

Literature references

  1. 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

External database links

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 YEATS

Alignments

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...

View options

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)
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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(258)
Full
(183893)
Representative proteomes UniProt
(285633)
RP15
(24537)
RP35
(62416)
RP55
(138140)
RP75
(189297)
Alignment:
Format:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(258)
Full
(183893)
Representative proteomes UniProt
(285633)
RP15
(24537)
RP35
(62416)
RP55
(138140)
RP75
(189297)
Raw Stockholm Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

Note: You can also download the data file for the tree.

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 View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Eberhardt R
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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 9.6
Trusted cut-off 22.0 9.6
Noise cut-off 21.9 9.5
Model length: 103
Family (HMM) version: 33
Download: download the raw HMM for this family

Species distribution

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Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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.

Protein Predicted structure External Information
A0A044QUH0 View 3D Structure Click here
A0A044QV04 View 3D Structure Click here
A0A044QZ73 View 3D Structure Click here
A0A044R6V4 View 3D Structure Click here
A0A044RHC8 View 3D Structure Click here
A0A044RNC5 View 3D Structure Click here
A0A044RZP7 View 3D Structure Click here
A0A044S3H3 View 3D Structure Click here
A0A044S3Z8 View 3D Structure Click here
A0A044S6L7 View 3D Structure Click here
A0A044S7R6 View 3D Structure Click here
A0A044S8X7 View 3D Structure Click here
A0A044SCQ4 View 3D Structure Click here
A0A044STT8 View 3D Structure Click here
A0A044T272 View 3D Structure Click here
A0A044T7N0 View 3D Structure Click here
A0A044TEZ7 View 3D Structure Click here
A0A044THW2 View 3D Structure Click here
A0A044TMV5 View 3D Structure Click here
A0A044TT55 View 3D Structure Click here
A0A044TTG8 View 3D Structure Click here
A0A044TTH8 View 3D Structure Click here
A0A044TUL0 View 3D Structure Click here
A0A044UM23 View 3D Structure Click here
A0A044UM30 View 3D Structure Click here
A0A044UUT1 View 3D Structure Click here
A0A044V2T0 View 3D Structure Click here
A0A044V7B6 View 3D Structure Click here
A0A044V965 View 3D Structure Click here
A0A044V9P8 View 3D Structure Click here
A0A044VBV4 View 3D Structure Click here
A0A061ACQ8 View 3D Structure Click here
A0A077YUP4 View 3D Structure Click here
A0A077YVK8 View 3D Structure Click here
A0A077YWI4 View 3D Structure Click here
A0A077YXH3 View 3D Structure Click here
A0A077YXU4 View 3D Structure Click here
A0A077YY87 View 3D Structure Click here
A0A077YZ09 View 3D Structure Click here
A0A077YZV8 View 3D Structure Click here