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39  structures 747  species 0  interactions 7331  sequences 115  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


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.

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...

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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
(48)
Full
(7331)
Representative proteomes UniProt
(11112)
RP15
(925)
RP35
(2359)
RP55
(5425)
RP75
(7474)
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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
(48)
Full
(7331)
Representative proteomes UniProt
(11112)
RP15
(925)
RP35
(2359)
RP55
(5425)
RP75
(7474)
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
(48)
Full
(7331)
Representative proteomes UniProt
(11112)
RP15
(925)
RP35
(2359)
RP55
(5425)
RP75
(7474)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Coggill P
Number in seed: 48
Number in full: 7331
Average length of the domain: 135.9 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 12.67 %

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 27.1 27.1
Trusted cut-off 27.1 27.1
Noise cut-off 27.0 27.0
Model length: 135
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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

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 PTEN_C2 domain has been found. There are 39 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
A0A044S0M8 View 3D Structure Click here
A0A044SJ16 View 3D Structure Click here
A0A044TDW8 View 3D Structure Click here
A0A077YZU9 View 3D Structure Click here
A0A0G2JY26 View 3D Structure Click here
A0A0K0DY91 View 3D Structure Click here
A0A0K0EDC2 View 3D Structure Click here
A0A0K0EPK3 View 3D Structure Click here
A0A0K0ESA3 View 3D Structure Click here
A0A0N4U6G3 View 3D Structure Click here
A0A0N4UH55 View 3D Structure Click here
A0A0N7KLN3 View 3D Structure Click here
A0A0P0VZN8 View 3D Structure Click here
A0A0P0W838 View 3D Structure Click here
A0A0R0FQ13 View 3D Structure Click here
A0A0R0IHF5 View 3D Structure Click here
A0A0R0KFD9 View 3D Structure Click here
A0A1D6F098 View 3D Structure Click here
A0A1D6HN65 View 3D Structure Click here
A0A1D6IIS0 View 3D Structure Click here
A0A1D6KED8 View 3D Structure Click here
A0A1D6KNK1 View 3D Structure Click here
A0A1D6MWQ7 View 3D Structure Click here
A0A1D6PZF6 View 3D Structure Click here
A0A1I9LNK8 View 3D Structure Click here
A0A2R8QIA5 View 3D Structure Click here
A0A2R8QPJ8 View 3D Structure Click here
A0A2R8QQZ0 View 3D Structure Click here
A0A368UGR4 View 3D Structure Click here
A0A368UH40 View 3D Structure Click here
A0A3P7FKC5 View 3D Structure Click here
A0A3Q0KFH0 View 3D Structure Click here
A0A5K4FF32 View 3D Structure Click here
A0A5S6PQX1 View 3D Structure Click here
A4I9V5 View 3D Structure Click here
B8JKC5 View 3D Structure Click here
D4ADC8 View 3D Structure Click here
E7F355 View 3D Structure Click here
E7FC59 View 3D Structure Click here
E9Q0S6 View 3D Structure Click here