The Eukaryote Linear Motif resource for Functional Sites in Proteins
LIG_MAPK_2 234
 
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Functional site class: MAPK docking motif
Functional site description: The docking interaction in the MAP kinase cascades is achieved through specific conserved regions on MAPKs (docking groove) and MAPK-interacting molecules (the MAPK docking motif). The docking motif is usually - but not always - the sequence of a substrate protein.
ELMs: LIG_MAPK_1 LIG_MAPK_2
Description: MAPK interacting molecules (e.g. MAPKKs, substrates, phosphatases) carry docking motifs that help to regulate specific interaction in the MAPK cascade.

The FXFP motif was first identified in the transcription factor LIN-1 (Jacobs at al, 1998): the motif is usually found C-terminal of the phosphorylation site. Binding and substrate phosphorylation can occur also in the absence of the proline residue; however its presence increases the binding affinity (Jacobs at al, 1999; Fantz et al, 2001).
Pattern: F.FP (Probability: 0.0000318)
Present in taxons: Eukaryota
Interaction Domain:

Pkinase (PF00069)
Protein kinase domain
(Stochiometry: 1 : 1)

o See 7 Instances for LIG_MAPK_2


o Abstract

MAPK (Mitogen-activated protein kinase) signalling pathways are characterized by a cascade of multiple kinases that contribute to regulate a variety of extracellular stimuli, thereby to control the cellular environment.

The MAPK family includes the ERKs (extracellular signal-regulated kinase), the JNKs (c-Jun N-terminal kinase), the p38 MAPKs and ERK5. The ERKs generally regulate cellular proliferation and differentiation processes in response to growth factors and other hormones while the JNKs and p38 MAPKs are primarily activated in response to extracellular stresses, such as U.V. irradiation, osmotic stress or inflammatory stimuli (Biondi and Nebreda, 2003).

MAPKs are serine/threonine kinases that tend to phosphorylate their substrates on S/T-P motif. As the sequence S/T-P is found in ~ 80% of all proteins additional factors are required to direct individual kinases towards the correct substrates (Bardwell, 2006). One way by which the MAPKs ensure their substrate specificity is by interaction through docking motifs, short amino acid stretches located on MAPK-interacting proteins.

The classical docking motif is characterized by a cluster of at least two positively charged amino acids followed by by a spacer of 2-to-6 residues from a hydrophobic-X-hydrophobic sequence, where the hydrophobic residues are long-chain aliphatics (usually Leu, Ile). Both in the spacer and in the sequence immediately C-terminal to the hydrophobic-X-hydrophobic element, there is a high propensity for the presence of Pro, Asn, and/or Gly, which are residues that are both turn-forming and helix-breaking (Bardwell, 2000).

Another type of docking motif is a short peptide containing the sequence FXFP that is usually downstream of the phosphorylation site. This motif was originally found to bind the ERK subfamily but lately it has been shown to promote the interaction with p38alpha and p38 beta2 (Jacobs et al., 1999; Galanis el at., 2001).

Substrates can contain the classical docking motif or the FXFP or often contain both. (Sharrocks et al., 2000).

o 9 selected references:

o 6 GO-Terms:

o 7 Instances for LIG_MAPK_2
(click table headers for sorting)
SequenceStartEndSubsequence
Instance LogicPDB Organism
RS3_HUMAN 77 80 LTAVVQKRFGFPEGSVELYA false positive 1S1H
 Homo sapiens (Human)
G5EDL0_CAEEL 420 423 PPSQSSTSFKFPSSTDSLKT true positive --- Caenorhabditis elegans
VINEX_MOUSE 630 633 RTSPRRSAFPFPITLQEPRS true positive --- Mus musculus (House mouse)
G5EFD2_CAEEL 309 312 SRSMNEPAFQFPDTAIDSSS true positive --- Caenorhabditis elegans
ELK1_HUMAN 395 398 PRSPAKLSFQFPSSGSAQVH true positive --- Homo sapiens (Human)
DUS1_HUMAN 339 342 RGTSTTTVFNFPVSIPVHST true positive --- Homo sapiens (Human)
ELK4_HUMAN 398 401 RLQGANTLFQFPSVLNSHGP true positive --- Homo sapiens (Human)

Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)

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