Summary: Phosphoinositide 3-kinase C2
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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
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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.
Phosphoinositide 3-kinase C2 Provide feedback
Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of PF00168 family.
Literature references
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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
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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
SCOOP: | C2 DOCK-C2 |
Similarity to PfamA using HHSearch: | C2 |
External database links
PROSITE: | PDOC50004 |
SCOP: | 1qmm |
SMART: | PI3K_C2 |
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 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 (16) |
Full (5739) |
Representative proteomes | UniProt (9280) |
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RP15 (815) |
RP35 (1901) |
RP55 (4275) |
RP75 (5814) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (16) |
Full (5739) |
Representative proteomes | UniProt (9280) |
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RP15 (815) |
RP35 (1901) |
RP55 (4275) |
RP75 (5814) |
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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.
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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.
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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: | 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
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: | 140 | ||||||||||||
Family (HMM) version: | 27 | ||||||||||||
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 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.