The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
14-3-3 ligand
Functional site description:
14-3-3 proteins interact with specific phosphoserine or phosphothreonine containing motifs.
ELMs with same func. site: LIG_14-3-3_1  LIG_14-3-3_2  LIG_14-3-3_3 
ELM Description:
The shorter mode 1 interacting phospho-motif for 14-3-3 proteins with key conservation RxxSxP. Pro is excluded -1 and +1 of the pSer due to tight backbone interactions. Other residue preferences in the x positions affect binding affinity and some combinations may be disfavoured. The typical kinases phosphorylating mode 1 peptides are likely to have a positive charge preference preceding the phosphorylated residue.
Pattern: R.[^P]([ST])[^P]P
Pattern Probability: 0.0008077
Present in taxons: Arabidopsis thaliana Bos taurus Caenorhabditis elegans Dictyostelium discoideum Eukaryota Gallus gallus Homo sapiens Mus musculus Petroselinum crispum Rattus norvegicus Saccharomyces cerevisiae Schizosaccharomyces pombe Xenopus laevis
Interaction Domain:
14-3-3 (PF00244) 14-3-3 protein (Stochiometry: 1 : 1)
PDB Structure: 1QJB
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1QJB" title="" target="_blank"><img src="/media/pdb.ico.png"/>1QJB</a>
o See 16 Instances for LIG_14-3-3_1
o Abstract
The 14-3-3 proteins constitute a family of conserved proteins present in all eukaryotic organisms so far investigated, including seven isotypes in human cells. They occur as homo- or heterodimers. They are involved in important cellular processes such as signal transduction, cell-cycle control, apoptosis, stress response and malignant transformation. More than one hundred different binding partners for these proteins have been reported so far. 14-3-3 proteins were the first signaling molecules to be identified as discrete phosphoserine/threonine binding modules, although cases of phosphorylation-independent interaction have been reported. While many details of the biochemical and cellular functions of 14-3-3 proteins remain to be elucidated, they are known to act as adaptor molecules to mediate protein-protein interactions, the subcellular localisation and to regulate enzyme activities. Though 14-3-3 proteins perform different functions for different ligands, general mechanisms of 14-3-3 action include changes in activity of bound ligands, altered association of bound ligands with other cellular components, and changes in intracellular localization of 14-3-3-bound cargo.

The classical mode 1 and mode 2 binding motifs are compatible with phosphorylation by e.g. PKA, PKB and other kinases with a positive charge preference and it is likely that these are the typical kinases phosphorylating 14-3-3-binding sites. On the other hand the C-terminal peptide from plant H+ ATPases - QSYpTV* - lacks a positive charge and will be phosphorylated by another class of kinase. This does raise the question of how often non-canonical 14-3-3 binding peptides will lack a positive residue preceding the phosphorylation site.

14-3-3 proteins are targeted by certain fungal toxins and bacterial virulence factors. Fusicoccin toxin stabilises an H+ ATPase phosphopeptide interaction with 14-3-3 (Wurtele,2003). The non-phosphorylated Pseudomonas exoS peptide LLDALDL binds in the reverse orientation to the phosphorylated peptides and it is possible that there are cellular equivalents of this binding mode (Ottmann,2007). It is thought that all non-phosphorylated peptides will bind in the reverse orientation.
o 17 selected references:

o 14 GO-Terms:

o 16 Instances for LIG_14-3-3_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P54253 ATXN1
ATX1_HUMAN
772 777 KPAATRKRRWSAPESRKLEK TP 4 Homo sapiens (Human)
2 
P04049 RAF1
RAF1_HUMAN
618 623 HSLPKINRSASEPSLHRAAH TP 1 Homo sapiens (Human)
1 
O35147 Bad
BAD_RAT
134 139 ELSPFRGRSRSAPPNLWAAQ TP 1 Rattus norvegicus (Norway rat)
1 
Q99683 MAP3K5
M3K5_HUMAN
963 968 AGSNEYLRSISLPVPVLVED TP 1 Homo sapiens (Human)
1 
P03076 Middle T anti
MT_POVM3
254 259 NPTYSVMRSHSYPPTRVLQQ TP 2 Mouse polyomavirus (strain 3)
1 
P98177 FOXO4
FOXO4_HUMAN
29 34 FEPQSRPRSCTWPLPRPEIA TP 3 Homo sapiens (Human)
1 
1 
Q9EPK5 Wwtr1
WWTR1_MOUSE
86 91 AGGAQHVRSHSSPASLQLGT TP 3 Mus musculus (House mouse)
O15151 MDM4
MDM4_HUMAN
364 369 NDVPDCRRTISAPVVRPKDA TP 3 Homo sapiens (Human)
1 
1 
P04049 RAF1
RAF1_HUMAN
256 261 GSLSQRQRSTSTPNVHMVST TP 2 Homo sapiens (Human)
1 
2 
P46937 YAP1
YAP1_HUMAN
124 129 ALTPQHVRAHSSPASLQLGA TP 2 Homo sapiens (Human)
1 
P46937-2 YAP1
YAP1_HUMAN
124 129 ALTPQHVRAHSSPASLQLGA TP 3 Homo sapiens (Human)
Q61337 Bad
BAD_MOUSE
109 114 GAMETRSRHSSYPAGTEEDE TP 3 Mus musculus (House mouse)
Q61337 Bad
BAD_MOUSE
133 138 ELSPFRGRSRSAPPNLWAAQ TP 5 Mus musculus (House mouse)
1 
1 
P08965 mei2
MEI2_SCHPO
435 440 FGSVPLGRTESSPAWGTSGY TP 4 Schizosaccharomyces pombe 972h-
1 
2 
P46938 Yap1
YAP1_MOUSE
109 114 ALTPQHVRAHSSPASLQLGA TP 2 Mus musculus (House mouse)
1 
Q9GZV5 WWTR1
WWTR1_HUMAN
86 91 AGGAQHVRSHSSPASLQLGT TP 4 Homo sapiens (Human)
1 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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