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25  structures 146  species 0  interactions 847  sequences 39  architectures

Family: PTEN_C2 (PF10409)

Summary: C2 domain of PTEN tumour-suppressor protein

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C2 domain of PTEN tumour-suppressor protein Provide feedback

This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (PF00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane [1].

Literature references

  1. Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP; , Cell. 1999;99:323-334.: Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. PUBMED:10555148 EPMC:10555148


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR014020

Tensins constitute an eukaryotic family of lipid phosphatases that are defined by the presence of two adjacent domains: a lipid phosphatase domain and a C2-like domain. The tensin-type C2 domain has a structure similar to the classical C2 domain (see INTERPRO) that mediates the Ca2+-dependent membrane recruitment of several signalling proteins. However the tensin-type C2 domain lacks two of the three conserved loops that bind Ca2+, and in this respect it is similar to the C2 domains of PKC-type [PUBMED:11395408, PUBMED:11858936]. The tensin-type C2 domain can bind phopholipid membranes in a Ca2+ independent manner [PUBMED:10555148]. In the tumour suppressor protein PTEN, the best characterised member of the family, the lipid phosphatase domain was shown to specifically dephosphorylate the D3 position of the inositol ring of the lipid second messenger, phosphatydilinositol-3-4-5-triphosphate (PIP3). The lipid phosphatase domain contains the signature motif HCXXGXXR present in the active sites of protein tyrosine phosphatases (PTPs) and dual specificity phosphatases (DSPs). Furthermore, two invariant lysines are found only in the tensin-type phosphatase motif (HCKXGKXR) and are suspected to interact with the phosphate group at position D1 and D5 of the inositol ring [PUBMED:11395408, PUBMED:10555148].

The C2 domain is found at the C terminus of the tumour suppressor protein PTEN (phosphatidyl-inositol triphosphate phosphatase). This domain may include a CBR3 loop, indicating a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc suggesting that the C2 domain productively positions the catalytic part of the protein on the membrane. The crystal structure of the PTEN tumour suppressor has been solved [PUBMED:10555148]. The lipid phosphatase domain has a structure similar to the dual specificity phosphatase (see INTERPRO). However, PTEN has a larger active site pocket that could be important to accommodate PI(3,4,5)P3.

Proteins known to contain a phosphatase and a C2 tensin-type domain are listed below:

  • Tensin, a focal-adhesion molecule that binds to actin filaments. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton.
  • Phosphatase and tensin homologue deleted on chromosome 10 protein (PTEN). It antagonizes PI 3-kinase signalling by dephosphorylating the 3-position of the inositol ring of PI(3,4,5)P3 and thus inactivates downstream signalling. It plays major roles both during development and in the adult to control cell size, growth, and survival.
  • Auxilin. It binds clathrin heavy chain and promotes its assembly into regular cages.
  • Cyclin G-associated kinase or auxilin-2. It is a potential regulator of clathrin-mediated membrane trafficking.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 9 members:

Aida_C2 B9-C2 C2 CC2D2AN-C2 CEP76-C2 DOCK-C2 NT-C2 PI3K_C2 PTEN_C2

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
(61)
Full
(847)
Representative proteomes NCBI
(790)
Meta
(5)
RP15
(147)
RP35
(223)
RP55
(334)
RP75
(477)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Format an alignment

  Seed
(61)
Full
(847)
Representative proteomes NCBI
(790)
Meta
(5)
RP15
(147)
RP35
(223)
RP55
(334)
RP75
(477)
Alignment:
Format:
Order:
Sequence:
Gaps:
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Download options

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
(61)
Full
(847)
Representative proteomes NCBI
(790)
Meta
(5)
RP15
(147)
RP35
(223)
RP55
(334)
RP75
(477)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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: Gene3D, pdb_1d5r
Previous IDs: none
Type: Family
Author: Finn RD, Coggill PC
Number in seed: 61
Number in full: 847
Average length of the domain: 136.70 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 15.32 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.5 25.5
Trusted cut-off 25.5 25.8
Noise cut-off 25.0 25.4
Model length: 134
Family (HMM) version: 4
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 PTEN_C2 domain has been found. There are 25 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 seqence.

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