Phosphatase Subfamily PHLPP
Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PHLPP (PH domain and leucine rich repeat protein phosphatase)
PHLPP stands for PH domain and leucine rich repeat protein phosphatase.
Contents
Evolution
The PHLPP subfamily is found across bilateria. Human has two members, PHLPP1/SCOP andPHLPP2, which most likely originated from vertebrate whole genome duplication.
Domain
The PHLPP subfamily has a N-terminal PH domain, leucine rich repeats, phosphatase domain, and a C-terminal PDZ-domain binding motif.
Functions
PHLPP1 and PHLPP2 dephosphorylates and inactivates kinases of AKT family at Ser-473 of human AKT1 [1, 2]. PHLPP1 prefers to dephosphorylate AKT2 and PHLPP2 prefers AKT3 [2]. The position Ser-473 located in hydrophobic motif is conserved across bilateria and among the three human members. It is also found in one sponge AKT, but not all three sponge AKTs (see alignment in KinBase).
The PHLPP subfamily also dephosphorylates PKC at Ser-660 of human PKC-beta [3]. The position Ser-660 located in hydrophobic motif is conserved across metazoa (replaced by Thr in sea urchin) (see KinBase).
PHLPP1 and PHLPP2 are implicated in different kinds of cancers, such as colon cancer [4], hypopharyngeal squamous cell carcinomas [5].
References
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