Phosphatase Subfamily Auxilin

Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily Auxilin

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Evolution

Auxillins are metazoan-specific, and lost from nematodes.

Domain Structure

Most auxillins are 1000-1500 AA long, with an N-terminal GAK kinase domain, a PTEN-like phosphatase domain in the middle, and a DnaJ domain at the very C-terminus. One of the two human homologs, DNAJC6/Auxillin-1 has lost the kinase domain

Functions

Human GAK is known as Cyclin G-Associated Kinase, and associated with Cyclin G and CDK5 [1, 2, 2, 3, 4, 4, 4, 4, 5, 5, 5, 5, 5, 5, 6, 6, 6, 7, 7, 8, 9, 10, 10, 10, 10, 10, 11, 11, 12, 12, 13, 14, 15, 16, 16, 17, 17, 17, 18, 19, 20, 21, 21, 22, 23, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 40, 41, 42, 42, 43, 44, 45, 46, 47, 48]. GAK also binds AP1 and is required for endosomal sorting [49]. GAK can also localize to the nucleus and is required in a clathrin-dependent manner for mitosis [50].

Little is known about the phosphatase or kinase activities of auxilins, though one report shows that GAK phosphorylates and activates the PP2A complex [51]. The phosphatase domains of both are predicted to be inactive (HCx5R changed to HCx5A in both), though the human GAK phosphatase domain has been reported to bind phospholipids, which are also involved in clathrin-coated vesicles [52].

References

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