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247  structures 1409  species 0  interactions 5739  sequences 144  architectures

Family: PI3K_C2 (PF00792)

Summary: Phosphoinositide 3-kinase C2

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.

Phosphoinositide 3-kinase C2 Provide feedback

Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of PF00168 family.

Literature references

  1. Domin J, Waterfield MD; , FEBS Lett 1997;410:91-95.: Using structure to define the function of phosphoinositide 3-kinase family members. PUBMED:9247130 EPMC:9247130

  2. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD; , Trends Biochem Sci 1997;22:267-272.: Phosphoinositide 3-kinases: a conserved family of signal transducers. PUBMED:9255069 EPMC:9255069

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002420

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that phosphorylate 4,5-bisphonate (PI(4,5) P2 or PIP2) at the 3-position of the inositol ring, and thus generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which, in turns, initiates a vast array of signaling events. PI3Ks can be grouped into three classes based on their domain organisation. Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit of either the p85 type (associated with the class IA p110 isoforms p110alpha, p110beta or p110delta) or the p101 type (associated with the class IB p110 isoform p110gamma). Common to all catalytic subunits are an N-terminal adaptor-binding domain (ABD) that binds to p85, a Ras- binding domain (RBD), a putative membrane-binding domain (C2), a helical domain of unknown function, and a kinase catalytic domain. Class II PI3Ks lack the ABD domain and are distinguished by a carboxy terminal C2 domain. Class III enzymes lack the ABD and RBD domains [ PUBMED:17626883 , PUBMED:18079394 , PUBMED:20081827 , PUBMED:10580505 ].

The PI3K-type C2 domain is an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets [ PUBMED:17626883 , PUBMED:18079394 , PUBMED:20081827 , PUBMED:10580505 ].

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


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.

Representative proteomes UniProt
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Representative proteomes UniProt

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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.

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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...


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: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: SMART, Griffiths-Jones SR
Number in seed: 16
Number in full: 5739
Average length of the domain: 137.7 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 12.56 %

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 26.4 26.4
Trusted cut-off 26.4 26.4
Noise cut-off 26.3 26.3
Model length: 140
Family (HMM) version: 27
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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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The tree shows the occurrence of this domain across different species. More...


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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 PI3K_C2 domain has been found. There are 247 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
A0A044RGA8 View 3D Structure Click here
A0A044TT55 View 3D Structure Click here
A0A044VIC1 View 3D Structure Click here
A0A077ZAT8 View 3D Structure Click here
A0A077ZJ99 View 3D Structure Click here
A0A0D2HB63 View 3D Structure Click here
A0A0G2K344 View 3D Structure Click here
A0A0G2K5T3 View 3D Structure Click here
A0A0G2L6J0 View 3D Structure Click here
A0A0K0DS90 View 3D Structure Click here
A0A0K0EAR4 View 3D Structure Click here
A0A0N4UB96 View 3D Structure Click here
A0A0N4UIF9 View 3D Structure Click here
A0A175WDA2 View 3D Structure Click here
A0A183XRJ2 View 3D Structure Click here
A0A1C1C754 View 3D Structure Click here
A0A1D6Q0F2 View 3D Structure Click here
A0A1D8PDV7 View 3D Structure Click here
A0A2R8QSP1 View 3D Structure Click here
A0A3P7DW01 View 3D Structure Click here
A0A3P7EFQ4 View 3D Structure Click here
A0A3Q0KLC8 View 3D Structure Click here
A0A3Q0KRX5 View 3D Structure Click here
A0A3Q0KT10 View 3D Structure Click here
A0A5K4EWU8 View 3D Structure Click here
A0A5K4EWZ4 View 3D Structure Click here
A0A5S6PC71 View 3D Structure Click here
A0A5S6PLK3 View 3D Structure Click here
A0A5S6PLS0 View 3D Structure Click here
A0A7I4KHX6 View 3D Structure Click here
A4HVU4 View 3D Structure Click here
C0P0L3 View 3D Structure Click here
C1GZW6 View 3D Structure Click here
D3ZFJ0 View 3D Structure Click here
D3ZTF6 View 3D Structure Click here
D3ZVF3 View 3D Structure Click here
D4A5Q1 View 3D Structure Click here
E7F251 View 3D Structure Click here
E9QAN8 View 3D Structure Click here
F1Q9F3 View 3D Structure Click here