TI - FIP200 , a possible counterpart of yeast Atg17 ? . AB - It was previously shown that FIP200 interacted with TSC1 and PHOSphorylation of S6 kinase after amino acid stimulation was impaired in cells treated with FIP200 siRNA . However , this effect was observed only moderately in FIP200-/- MEFs . We also failed to detect clear defect in this pathway as we tested the PHOSphorylation levels of 4E-BP1 ( Fig 5 A ) . There might be adaptation to the FIP200-deficient conditions in permanently knocked out cells . However , our present study does not exclude the possibility that FIP200 functions with the TSC complex . FIP200 may function both upstream and downstream of mTOR , but the downstream effect can be dominant when we analyze autophagy . As FIP200 interacts with ULK1 and 2 and is essential for autophagy , one might speculate that this protein is a counterpart of yeast Atg13 or 17 . Indeed , although FIP200 ( 1594 aa ) is much larger than Atg17 ( 417 aa ) , FIP200 shares several features with yeast Atg17 . First , both Atg17 and FIP200 have multiple coiled-coil domains . Second , just as Atg17 is required for Atg1 kinase activity , the PHOSphorylation status of ULK1 is reduced in FIP200-deficient cells , which may indicate diminished ULK1 activity ( Fig 8 ) . It is therefore likely that Atg17 and FIP200 can support the function of Atg1 and ULKs , respectively . We also found that ULK1 kinase activity per cell was reduced in FIP200-/- cells ( unpublished data ) . However , as ULK1 expression level itself was also lower in FIP200-/- cells than in wild-type cells ( Fig 8 ) , we could not conclude how much specific activity of ULK1 reduced in the absence of FIP200 . Third , the C-terminal region of ULK1 is essential for both FIP200 interaction and ULK1 puncta formation , suggesting that interaction with FIP200 is important for membrane targeting . This is consistent with the previous finding that yeast Atg17 is required for PAS targeting of Atg1 , which is particularly apparent in the atg11 mutant . Fourth , FIP200 has multiple binding partners other than ULK1 and 2 . Similarly , systematic analyses of yeast protein interactions by two hybrid analysis and mass spectrometry identified many potential Atg17 -interacting proteins , some of which are unrelated to autophagy . Therefore , both Atg17 and FIP200 may function as a scaffold for multiple proteins . Finally , homologues of Atg17 are present in Kluyveromyces lactis and Eremothecium gossypii , where FIP200 homologue is missing . On the other hand , FIP200 homologues are found in Homo sapiens , Mus musculus , Gallus gallus and D.melanogaster , where Atg17 homologues are absent , but not in Saccharomyces cerevisiae . This mutual exclusiveness suggests that these two groups of proteins may serve similar functions for which one , but not both , proteins are required . Identification and analysis of a functional homologue of mammalian Atg13 , a critical factor of this complex , will further clarify the functional relationship between yeast and mammalian Atg1 complex .