The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
Raptor interacting motif
Functional site description:
At least one (but perhaps more) motifs interact with raptor as part of TOR pathway function. TOR is a kinase that regulates translation in a pathway with broad effects on many other cellular processes. The best known raptor-binding motif is TOS (the TOR signalling motif).
ELM Description:
The TOS motif is found in substrates of the mTOR kinase. TOS interacts with the WD40-containing adaptor protein Raptor that is required to bring TOR together with its substrates. This motif expression is derived from the conservation observed in the 4E-BP translation initiation factors and the ribosomal s6-beta kinases and shows a strong beta amphipathicity. The motif alternates between hydrophobic and negatively charged residues. Although the structure of a TOS-Raptor complex is not yet known, the conservation might imply that the motif is bound in a sandwiched pocket. The terminal charged moiety can be either the carboxy-terminus (4E-BP1,2,3) or an amino acid (S6-beta kinase). TOS motifs reported in Hif1-alpha, Pld2 and AKTS1 do not match the motif expression in the ELM resource. The TOS motif is clearly not present in many proteins but the NUMB and NUMBL proteins do contain plausible candidates that might be worth investigating. The TOS motif as described here is found in Metazoa, slime mould and one basidiomycete, but not in other Fungi. If the phylogenetic distribution is larger, then the TOS motif will have diverged indifferent lineages.
Pattern: F[EDQS][MILV][ED][MILV]((.{0,1}[ED])|($))
Pattern Probability: 0.0000207
Present in taxon: Eukaryota
Interaction Domain:
WD40 (PF00400) WD domain, G-beta repeat (Stochiometry: 1 : 1)
o See 5 Instances for DOC_WD40_RPTOR_TOS_1
o Abstract
The mammalian target of rapamycin mTOR, also known as FRAP, is a member of the PIK-related superfamily of protein serine/theronine kinases that was first identified in Saccharomyces cerevisiae (Oshiro,2007). The TOR pathway is an emerging target for the treatment of cancer, diabetes and obesity. TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many of them are phosphorylated indirectly. TOR participates in at least two distinct multiprotein complexes TORC1 and TORC2. These complexes play important role in the regulation of cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription (Beugnet,2003). Two short motifs have been reported in the targets of TOR, the TOS motif (TOR signalling motif) and the RAIP motif. However, the RAIP motif is not characterised well enough to be included in ELM.
In mammals mTOR, (mammalian TOR), regulates protein synthesis through the phosphorylation and inactivation of the repressor of mRNA translation, eukaryotic initiation factor 4E-binding protein (4E-BP1), and through the phosphorylation and activation of S6 kinase (S6K1). mTOR exists in two distinct complexes within cells: one (mTORC1) that contains mTOR, mLst8 and raptor and another (mTORC2) containing mTOR, mLst8, mSin1 and rictor (Schalm,2002). In order to phosphorylate its substrates in the TORC1 complex, mTOR needs an adaptor protein (raptor) that binds to S6K1 and 4E-BP1 (16824195). The interaction of raptor with S6K1 and 4E-BP1 is mediated by the TOS motif that is present in the N-terminus of S6-beta kinases and C-terminus of 4E-BP1. The TOS motif is currently only known from metazoan organisms. However, the TORC1 complex and highly conserved raptor orthologues are present in both Saccharomyces cerevisiae (Kog1) and Schizosaccharomyces pombe (Mip1). It is possible that the TOS motif exists in other Eukaryotic lineages but diverges from the metazoan motif pattern and so needs rediscovery.
o 10 selected references:

o 4 GO-Terms:

o 5 Instances for DOC_WD40_RPTOR_TOS_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q13541 EIF4EBP1
114 118 RNSPEDKRAGGEESQFEMDI TP 5 Homo sapiens (Human)
5 10 MAAVFDLDLETEEGSEGEGE TP 2 Homo sapiens (Human)
P23443 RPS6KB1
28 33 AEDMAGVFDIDLDQPEDAGS TP 2 Homo sapiens (Human)
Q13542 EIF4EBP2
116 120 LNNHDRKHAVGDDAQFEMDI TP 4 Homo sapiens (Human)
O60516 EIF4EBP3
96 100 LKEQETEEEIPDDAQFEMDI TP 4 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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