The Eukaryote Linear Motif resource for Functional Sites in Proteins
LIG_RAPTOR_TOS_1 246
 
 << LIG_PTB_Phospho_1 <<  Menu  >> LIG_Rb_LxCxE_1 >> 
 
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).
ELMs: LIG_RAPTOR_TOS_1
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])|($)) (Probability: 0.0000207)
Present in taxons: Eukaryota
Interaction Domain:

WD40 (PF00400)
WD domain, G-beta repeat
(Stochiometry: 1 : 1)

o See 5 Instances for LIG_RAPTOR_TOS_1


o Abstract

mTOR the mammalian target of rapamycin, also known as FRAP, is a member of a superfamily of protein serine/theronine kinases termed PIK-related (Oshiro, 2007), that was first identified in Saccharomyces cerevisiae. The TOR pathway is an emerging target for the treatment of cancer, diabetes and obesity (Eguchi S, 2007).

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 A, 2003).

Two short motifs have been reported in the targets of TOR, the TOS motif (TOR signalling motif) and the RAIP motif. (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 S, 2002).

In order to phosphorylate its substrates in the TORC1 complex, mTOR needs an adaptor protein (raptor), that’s binds to S6K1 and 4E-BP1 (Eguchi et al., 2006). 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 budding yeast (Kog1) and fission yeast (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 LIG_RAPTOR_TOS_1
(click table headers for sorting)
SequenceStartEndSubsequence
Instance LogicPDB Organism
KS6B2_HUMAN 5 10 MAAVFDLDLETEEGSEGEGE true positive --- Homo sapiens (Human)
KS6B1_HUMAN 28 33 AEDMAGVFDIDLDQPEDAGS true positive --- Homo sapiens (Human)
4EBP2_HUMAN 116 120 LNNHDRKHAVGDDAQFEMDI true positive --- Homo sapiens (Human)
4EBP3_HUMAN 96 100 LKEQETEEEIPDDAQFEMDI true positive --- Homo sapiens (Human)
4EBP1_HUMAN 114 118 RNSPEDKRAGGEESQFEMDI true positive --- Homo sapiens (Human)
Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)
feedback@elm.eu.org