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PROSITE documentation PDOC51181 [for PROSITE entry PS51182]

Tensin phosphatase and C2 domain profiles





Description

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 lacks the canonical Ca(2+) ligands found in classical C2 domains (see <PDOC00380>), and in this respect it is similar to the C2 domains of PKC-type [1,2]. The tensin-type C2 domain can bind phospholipid membranes in a Ca(2+) independent manner [3]. In the tumor suppressor protein PTEN, the best characterized 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 [1,3].

The crystal structure of the PTEN tumor suppressor has been solved (see <PDB:1D5R>) [3]. The lipid phosphatase domain has a structure similar to the dual specificity phosphatase (see <PDOC00323>). However, PTEN has a larger active site pocket that could be important to accomodate PI(3,4,5)P3. The tensin-type C2 domain has a structure similar to the classical C2 domain that mediates the Ca2+ dependent membrane recruitment of several signaling proteins. However the tensin-type C2 domain lacks two of the three conserved loops that bind Ca2+.

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.

Each profile covers the whole domain for which it was developed.

Note:

PTEN homologues in fungi have the tensin phosphatase domain, but they lack the C2 domain.

Last update:

February 2006 / First entry.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

C2_TENSIN, PS51182; C2 tensin-type domain profile  (MATRIX)

PPASE_TENSIN, PS51181; Phosphatase tensin-type domain profile  (MATRIX)


References

1AuthorsMaehama T. Taylor G.S. Dixon J.E.
TitlePTEN and myotubularin: novel phosphoinositide phosphatases.
SourceAnnu. Rev. Biochem. 70:247-279(2001).
PubMed ID11395408
DOI10.1146/annurev.biochem.70.1.247

2AuthorsLeslie N.R. Downes C.P.
TitlePTEN: the down side of PI 3-kinase signalling.
SourceCell. Signal. 14:285-295(2002).
PubMed ID11858936

3AuthorsLee J.O. Yang H. Georgescu M.M. Di Cristofano A. Maehama T. Shi Y. Dixon J.E. Pandolfi P. Pavletich N.P.
TitleCrystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
SourceCell 99:323-334(1999).
PubMed ID10555148



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