| Accession: | |
|---|---|
| Functional site class: | Adaptin binding Endosome-Lysosome-Basolateral sorting signals |
| Functional site description: | Endocytosis and/or vesicular sorting signals for membrane proteins. Depending on organism, cell type as well as the nature of the adaptin complex bound, they can target either to cell surface or to specific, internal membrane-bound organelles (endosomes, lysosomes, melanosomes, synaptic vesicles, etc.) All these motifs are believed to bind to the sigma subunit of activated adaptin complexes (AP-1, AP-2 and AP-3). These clathrin-associated complexes are ancient and found in most eukaryotes. Dileucine motifs are variable (especially at their negatively charged positions and at the hydrophobic residues) and the various motif subtypes tend to have slightly different functions (Mattera,2011). One should avoid confusing the adaptin sigma-binding classical dileucine motifs discussed here, and the GGA-binding lysosomal targeting motifs (sometimes also called dileucine motifs). |
| ELMs with same func. site: | TRG_DiLeu_BaEn_1 TRG_DiLeu_BaEn_2 TRG_DiLeu_BaEn_3 TRG_DiLeu_BaEn_4 TRG_DiLeu_BaLyEn_6 TRG_DiLeu_LyEn_5 |
| ELM Description: | The strict version of the dileucine motif is one of the most common variants, preferentially binding to AP-1 or AP-2 complexes. These motifs generally allow the proteins to reach the cell surface in multicellular animals, such as a basolateral localization in epithelia and/or reversible endocytosis into early endosomes. In neurons, such motifs are sometimes involved in somato-dendritic cell surface localization. The lack of a proline immediately preceding the two hydrophobic positions distinguishes these motifs from obligatory lysosomal (or axonal) targeting signals. Although historically called acidic dileucine motifs, one or both hydrophobic positions can also be exchanged for hydrophobic amino acids other than leucine. On the other hand, dileucine motifs are more restrictive at their N-terminal ends. Contrary to earlier suggestions (Kelly,2008), it has now become clearer that dileucine motifs strongly prefer glutamate versus aspartate at their first position (an observation also supported by evolutionary conservation analyses). Structurally, this is due to the distance between the motif main chain and the charged surface of the sigma subunit, with Asp being too short (4P6Z_V; 4NEE_E; 6DFF_L; 6OWT_N). Conversely, Asp-carrying motifs need additional strengthening features (such as the above-mentioned proline) to remain functional. These divergent instances are now also treated as a separate motif subtype in ELM. Addition of one or more extra glutamates before the first Glu can also act as a strengthening feature, although it is not required for functionality if the hydrophobic contact points are otherwise optimal. The classical motif variant apparently also exists in diverse eukaryotes, including fungi and plants. The latter dileucine motifs were implicated in membrane protein sorting to vacuoles or tonoplasts (Wang,2014). Thus, in these organisms, the motif appears to be functionally equivalent to other dileucine motif subtypes, including lysosomal targeting signals. |
| Pattern: | E..[^P]L[LIVM] |
| Pattern Probability: | 0.0009700 |
| Present in taxon: | Eukaryota |
| Interaction Domain: |
Clat_adaptor_s (PF01217)
Clathrin adaptor complex small chain
(Stochiometry: 1 : 1)
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