The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
CAP-Gly Domain Ligands
Functional site description:
CAP-Gly domains are central to the regulatory interactions at the plus ends of microtubules. They are found in a number of microtubule-interacting proteins with very diverse architectures. CAP-Gly domains harboring an intact GKNDG binding site motif recognise C-terminal EEY/F$ or WxxGCY$ C-terminal motifs of EB proteins, alpha-tubulin, CLIP-170 and SLAINs. In the case of alpha-tubulin, the terminal tyrosine residue is subject to a cycle of detyrosination-tyrosination.
ELMs with same func. site: LIG_CAP-Gly_1  LIG_CAP-Gly_2 
ELM Description:
Short, acidic and aromatic carboxy terminal sequence found in a small group of microtubule-associated-proteins. The EEY/F$ motif is highly conserved and so far limited to a few known proteins, alpha-tubulin, EB proteins and CLIP170. The current regular expression is mainly modelled on the metazoan sequences. While there is the possibility that the motif has drifted in other lineages, it retrieves almost all alpha-tubulins in Swiss-Prot. It has a low but finite rate of false positives.
Pattern: [ED].{0,2}[ED].{0,2}[EDQ].{0,1}[YF]$
Pattern Probability: 0.0000040
Present in taxon: Eukaryota
Interaction Domain:
CAP_GLY (PF01302) CAP-Gly domain (Stochiometry: 1 : 1)
PDB Structure: 2E4H
o See 3 Instances for LIG_CAP-Gly_1
o Abstract
The cytoskeleton-associated protein-glycine-rich domain (CAP-Gly; PF01302) is a small, approximately 80-residue protein module conserved in organisms from yeast to human. CAP-Gly domains have central functions in many proteins, including cytoplasmic linker proteins (CLIPs and CLIPRs), the large subunit of the dynactin complex (DCTN1, or p150glued), tubulin folding cofactors B and E, centrosome-associated protein-350 (CAP350), the kinesin protein KIF13b and the familial cylindromatosis tumor suppressor CYLD. These proteins are implicated in essential cellular processes such as chromosome segregation, establishment and maintenance of cell polarity, intracellular organelle and vesicle transport, cell migration, intracellular signaling and oncogenesis.

The CAP-Gly domains of microtubule-associated-proteins (MAPs) are characterized by the conserved GKNDG motif, which is responsible for targeting to the carboxy terminal EEY/F sequence motifs of CLIP-170, EB proteins, and alpha-tubulin. In addition to recognizing the terminal tyrosine the the CAP-Gly domains of CLIPs can also specifically recognize the preceding tryptophan residue of the C-terminal WxxGCY sequence motif of SLAINs.

The CAP-Gly EEY/F interaction is essential for the recruitment of the dynactin complex by CLIP170 (through p150glued) and for activation of CLIP-170. Furthermore, in most eukaryotic cells, the EEY/F tail of alpha-tubulin is subjected to an enzymatic detyrosination-tyrosination cycle in which the C-terminal tyrosine is repeatedly cleaved and added back. Suppression of this cycle leads to defects in spindle positioning, abnormal cell morphology, disorganized neuronal networks and tumour progression, underscoring the importance of this post-translational modification. Alpha-tubulin tyrosination has been linked to the ability of the microtubule plus end to recruit the CAP-Gly proteins p150glued, CLIP-170 and CLIP-115. Thus, the CAP-Gly-EEY/F interaction plays a fundamental role in the tubulin detyrosination-tyrosination cycle by controlling CAP-Gly proteins and as a consequence microtubule function.
o 10 selected references:

o 11 GO-Terms:

o 3 Instances for LIG_CAP-Gly_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q15691 MAPRE1
263 268 TDEGFVIPDEGGPQEEQEEY TP 7 Homo sapiens (Human)
P30622 CLIP1
1434 1438 CEICEMFGHWATNCNDDETF TP 5 Homo sapiens (Human)
443 451 YEEVGVDSVEGEGEEEGEEY TP 4 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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