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atg13 #3266

Closed ValWood closed 4 years ago

ValWood commented 4 years ago

from PMID:32909946 In S. cerevisiae

Atg1 kinase activity is controlled by other Atg proteins. In S. cerevisiae, two scaffold proteins Atg13 and Atg17 are required for activating Atg1 kinase during nitrogen starvation-induced non- selective bulk autophagy (Kamada et al., 2000; Yeh et al., 2010; Yeh et al., 2011). In this Atg1 acti- vation mode, monomeric Atg13, which can directly bind Atg1, makes multivalent interactions with dimeric Atg17, and thereby generates supramolecular assemblies, allowing concentration-depen- dent Atg1 autophosphorylation and autoactivation (Yeh et al., 2011; Fujioka et al., 2014; Yamamoto et al., 2016).

Unlike the situation in S. cerevisiae where Atg11 is dispensable for nitrogen starvation-induced bulk autophagy, in mammals, the Atg11-domain-harboring ortholog of S. cerevisiae Atg11, called FIP200 or RB1CC1, is essential for bulk autophagy (Hara et al., 2008; Ganley et al., 2009). Similarly, Atg11 orthologs in Drosophila melanogaster, Arabidopsis thaliana, and two yeast species Kluyveromyces marxianus and Schizosaccharomyces pombe are also indis- pensable for bulk autophagy (Kim et al., 2013; Sun et al., 2013; Li et al., 2014; Yamamoto et al., 2015). Mammalian and Drosophila Atg11/FIP200 proteins have been shown to promote Atg1 kinase activity (Ganley et al., 2009; Nagy et al., 2014). However, it is unclear how Atg11/FIP200 proteins enhance Atg1 kinase activity during bulk autophagy. Here, we show that in the fission yeast S. pombe, Atg11 but not Atg13 is required for the Atg1 kinase activity. Atg11 promotes Atg1 activation by dimerizing Atg1. Contrary to what has been widely assumed, we find that Atg1 activation can occur through cis-autophosphorylation of Atg1. These findings shed new light on the Atg1 activation mechanism and the molecular roles of Atg11/ FIP200 proteins.

So it seems that atg11 is a 'true' kinase regulator. Because at13 is not demonstrated to be a kinase activator in fission yeast, could you remove:

atg13 | autophagy associated protein kinase regulatory subunit Atg13 |   | activation of protein kinase activity |   | GO_Central | Schizosaccharomyces pombe | IBA | PANTHER:PTN001268151SGD:S000006389 | uncharacterized pthr13430 | protein |   | PMID:21873635 | 20170228

and

atg13 | autophagy associated protein kinase regulatory subunit Atg13 |   | activation of protein kinase activity |   | GO_Central | Schizosaccharomyces pombe | IBA | PANTHER:PTN001268151SGD:S000006389 | uncharacterized pthr13430 | protein |   | PMID:21873635 | 20170228

I will update the product and remove

atg13 | autophagy associated protein kinase regulatory subunit Atg13 |   | protein kinase regulator activity |   | PomBase | Schizosaccharomyces pombe | ISO | SGD:S000006389 | uncharacterized pthr13430 | protein |   | GO_REF:0000024 | 20181024

cheers Val

ValWood commented 4 years ago

Also if possible remove

atg13 | autophagy associated protein kinase regulatory subunit Atg13 |   | protein kinase binding |   | GO_Central | Schizosaccharomyces pombe | IBA | PANTHER:PTN001268151UniProtKB:O75143 | uncharacterized pthr13430 | protein |   | PMID:21873635 | 20171005

Since we are trying to avoid 'function' or 'family' specific binding terms (it is unsustainable to curate kinase binding fully, because 100's of proteins bind to 100's of kinases)

@pgaudet do you have any paint rules about transfer of binding terms? I thought binding wasn't transferred?

marcfeuermann commented 4 years ago

Here binding seemed consistent since atg13 it is part of the kinase complex. However, I understand that it is dangerous to propagate such terms. I've removed all the annotations as requested.

ValWood commented 4 years ago

Yeah ~I just don't use anything below 'protein binding' generally at all binding terms - but would be correct so I don't mind if it stays but I would filter it ;)