Pseudophosphatases

The page is incomplete.

Pseudophosphatases are proteins with strong structural and sequence similarity to active phosphatases, but that have sequence changes to the active site that make them catalytically inactive. They are found in all eukaryotes and tend to be deeply conserved, suggesting that they continue to have important biological functions.

List of pseudophosphatases

CC1 fold

CC1 fold phosphatases have an active site of CxxxxxR, and pseudophosphatases are computationally defined by loss of the C or R, which largely correlates with experimental evidence. Some CC1 phosphatases have dual domains, with one active and one an inactive pseudophosphatase domain. Some subfamilies that have pseudophosphatase domains in human include

• CDC14 subfamily, where CDC14A and CDC14B have dual phosphatase domains, with the first being a pseudophosphatase.
• Several myotubularin subfamilies are consistently inactive, and serve as regulators of active myotubularins. These include the MTMR5 (SBF), MTMR10 and MTMR9, covering 6 human genes.
• The DSP family includes pseudophosphatase subfamilies STYX, STYXL1, and a single member of the DSP3 subfamily, DUSP27.

HP fold

HP1 family

PFKFB subfamily

PFKFB has two enzymatic domains: 6-phosphofructo-2-kinase domain and fructose-2,6-bisphosphatase domain.

• Human PFKFB3 has low bisphosphatase activity, which is probably due to the R to S substitution at R motif [1, 2].
• Yeast PFK26 is inactive as indicated by the fructose-2,6-bisphosphatase moiety [3], which probably due to H to S substitution at RH motif.
• Yeast YLR345W is predicted to be inactive, since the substitution of H by C at RH motif is observed.

STS subfamily

C. elegans has an expansion in STS subfamily. It has five members, however, none of them has SH3 or UBA domain that are common among STSs. We observed substitutions in three STSs from RH..R..Hx to RC..A..Ds, --..K..Dn, RS..R..Ha, respectively.

Note: old version Pseudophosphatases (obsolete)

References

1. Manes NP and El-Maghrabi MR. The kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate. Arch Biochem Biophys. 2005 Jun 15;438(2):125-36. DOI:10.1016/j.abb.2005.04.011 |
2. Cavalier MC, Kim SG, Neau D, and Lee YH. Molecular basis of the fructose-2,6-bisphosphatase reaction of PFKFB3: transition state and the C-terminal function. Proteins. 2012 Apr;80(4):1143-53. DOI:10.1002/prot.24015 |
3. Kretschmer M, Langer C, and Prinz W. Mutation of monofunctional 6-phosphofructo-2-kinase in yeast to bifunctional 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase. Biochemistry. 1993 Oct 19;32(41):11143-8. DOI:10.1021/bi00092a025 |