Difference between revisions of "Phosphatase Subfamily Auxilin"
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===Evolution=== | ===Evolution=== | ||
| − | Auxillins are metazoan-specific, and lost from nematodes. | + | Auxillins are metazoan-specific, and lost from nematodes. The DNAJ domain appears to be much older and has orthologs in Arabidopsis (JAC1) and yeast (Swa2) that are also involved in clathrin uncoating, but lack phosphatase and kinase domains |
===Domain Structure=== | ===Domain Structure=== | ||
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#Scheele pmid=11470803 | #Scheele pmid=11470803 | ||
#Lee pmid=16895969 | #Lee pmid=16895969 | ||
| + | #Kalli pmid=23823232 | ||
</biblio> | </biblio> | ||
Revision as of 06:49, 28 December 2014
Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily Auxilin
Header
Evolution
Auxillins are metazoan-specific, and lost from nematodes. The DNAJ domain appears to be much older and has orthologs in Arabidopsis (JAC1) and yeast (Swa2) that are also involved in clathrin uncoating, but lack phosphatase and kinase domains
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]. Both GAK and DNAJC6 are genetically implicated in Parkinson's disease and GAK physically associates with the Parkinson's kinase, LRRK2. Human DNAJC6 is only expressed in neuronal tissues, but GAK is widespread, and generally expressed higher in non-neuronal tissue. GAK and DNAJC6 bind clathrin heavy chain and are found in and required for the function of clathrin-associated vesicles, particularly by interacting with Hsc70 in uncoating of the vesicles [2]. GAK also binds AP1 and is required for endosomal sorting [3]. GAK can also localize to the nucleus and is required in a clathrin-dependent manner for mitosis [4].
Little is known about the phosphatase or kinase activities of auxilins, though one report shows that GAK phosphorylates and activates the PP2A complex [5]. The phosphatase domains of both are predicted to be inactive (HCx5R changed to HCx5A in both), and both GAK and DNAJC6 phosphatase domains have been shown to bind phospholipids, which are also involved in clathrin-coated vesicles [6, 7].
References
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- Error fetching PMID 9013862:
- Error fetching PMID 11470803:
- Error fetching PMID 17538018:
- Error fetching PMID 19654208:
- Error fetching PMID 22262175:
- Error fetching PMID 16895969:
- Error fetching PMID 23823232:
