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:
Consensus derived from reported natural interactors which do not match the Mode 1 and Mode 2 ligands. Key conserved residues are missing. While the sequence range of 14-3-3 binders is certainly not fully defined, a pattern derived from outliers as here may be poorly predictive and matches should be treated with CAUTION. Validation is paramount.
Pattern: [RHK][STALV].([ST]).[PESRDIFTQ]
Pattern Probability: 0.0049480
Present in taxons: Arabidopsis thaliana Drosophila melanogaster Eukaryota Homo sapiens Mus musculus Nicotiana tabacum Rattus norvegicus Saccharomyces cerevisiae Schizosaccharomyces pombe Xenopus laevis
Interaction Domain:
14-3-3 (PF00244) 14-3-3 protein (Stochiometry: 1 : 1)
PDB Structure: 2V7D
<a style="white-space:nowrap;" href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2V7D" target="_blank"><img src="/media/pdb.ico.png"/>2V7D</a>
o See 22 Instances for LIG_14-3-3_3
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 11 selected references:

o 8 GO-Terms:

o 22 Instances for LIG_14-3-3_3
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
KSR1_MOUSE Ksr1 294 299 PSFPTLTRSKSHESQLGNRI TP 1 Mus musculus (House mouse)
1 
KSR1_MOUSE Ksr1 389 394 LPLARLRRTESVPSDINNPV TP 1 Mus musculus (House mouse)
1 
SLOB_DROME Slob 51 56 HKANGLKRSNSAIEFDVSAL TP 1 Drosophila melanogaster (Fruit fly)
1 
SLOB_DROME Slob 76 81 RQIYSSNRSASSEQDNSDLS TP 1 Drosophila melanogaster (Fruit fly)
2 
IRS1_HUMAN IRS1 371 376 RLHPPLNHSRSIPMPASRCS TP 1 Homo sapiens (Human)
1 
IRS1_HUMAN IRS1 638 643 DYMPMSPKSVSAPQQIINPI TP 1 Homo sapiens (Human)
1 
IRS1_HUMAN IRS1 267 272 MSDEFRPRSKSQSSSNCSNP TP 1 Homo sapiens (Human)
HDAC4_HUMAN HDAC4 629 634 GGHRPLSRAQSSPASATFPV TP 1 Homo sapiens (Human)
1 
RIM15_YEAST RIM15 1072 1077 FSLLDISRSSTPPLANPTNS TP 1 Saccharomyces cerevisiae (Baker"s yeast)
1 
PTN3_HUMAN PTPN3 356 361 VWNPAMRRSLSVEHLETKSL TP 1 Homo sapiens (Human)
1 
PTN3_HUMAN PTPN3 832 837 VNYVRSLRVDSEPVLVHCSA TP 1 Homo sapiens (Human)
1 
FOXO3_HUMAN FOXO3 29 34 FEPQSRPRSCTWPLQRPELQ TP 1 Homo sapiens (Human)
1 
ADA22_HUMAN ADAM22 831 836 ICENGRPRSNSWQGNLGGNK TP 2 Homo sapiens (Human)
1 
1 
ITB2_HUMAN ITGB2 755 760 NNDNPLFKSATTTVMNPKFA TP 4 Homo sapiens (Human)
1 
1 
FOXO3_HUMAN FOXO3 250 255 SGKAPRRRAVSMDNSNKYTK TP 1 Homo sapiens (Human)
1 
ADA22_HUMAN ADAM22 854 859 RGKRFRPRSNSTETLSPAKS TP 4 Homo sapiens (Human)
1 
MPIP2_HUMAN CDC25B 320 325 SKCQRLFRSPSMPCSVIRPI TP 5 Homo sapiens (Human)
1 
MPIP3_HUMAN CDC25C 213 218 VSRSGLYRSPSMPENLNRPR TP 4 Homo sapiens (Human)
1 
HG2A_HUMAN CD74 5 10 MHRRRSRSCREDQKPVMDDQ TP 2 Homo sapiens (Human)
1 
MDM4_HUMAN MDM4 339 344 SDCSKLTHSLSTSDITAIPE TP 3 Homo sapiens (Human)
1 
1 
KPCE_HUMAN PRKCE 343 348 SSPSEEDRSKSAPTSPCDQE TP 4 Homo sapiens (Human)
1 
1 
KPCE_HUMAN PRKCE 365 370 ELENNIRKALSFDNRGEEHR TP 4 Homo sapiens (Human)
1 
1 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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