| Accession: | |
|---|---|
| Functional site class: | Endosome-Lysosome-Basolateral sorting signals |
| Functional site description: | Sorting and internalisation signals directing type I transmembrane proteins from the cell surface or TGN to the lysosomal-endosomal compartment. Generally found near the C-terminus, they interact with adaptor protein complexes such as APs and GGAs. |
| ELMs with same func. site: | TRG_LysEnd_APsAcLL_1 TRG_LysEnd_APsAcLL_3 TRG_LysEnd_GGAAcLL_1 TRG_LysEnd_GGAAcLL_2 |
| ELM Description: | This targeting motif is interacting with the adaptor proteins AP1, AP2, AP3 and probably AP4 achieving internalisation and different levels of sorting within the cell. AP2 is involved in endocytosis at the plasma membrane, AP1 in sorting at the TGN, while AP3 is driving Lysosome/Endosome targeting. AP4 is suspected to be responsible for basolateral targeting. The di Leucine signals are used as signals in all these routes, in combination with other signals (for example Tyrosine based internalisation signals). It is unclear how the specificity for binding to APs is achieved but it seems that the bindign to AP2 is the less specific, allowing any missorted protein to be retrieved by internalisation. Experimental evidence for the specificty for AP binding is not always available, therefore a general pattern can be used to detect all signals of the type D/ExxxLL, and more specific patterns can be used (for AP3 for example, see TRG_LysEnd_APsAcLL_3). Remarkably, a D/ExxxLL motif is used by some virus proteins to be internalised, for ex HIV-1 protein Nef (Craig,1998). |
| Pattern: | [DERQ]...L[LVI] |
| Pattern Probability: | 0.0027577 |
| Present in taxon: | Vertebrata |
| Interaction Domain: |
Clat_adaptor_s (PF01217)
Clathrin adaptor complex small chain
(Stochiometry: 1 : 1)
|
 Abstract |
Lysosomes are acidic compartments within cells where lumenal hydrolases degrade endogenous and internalized macromolecules. Most soluble hydrolases transit by the Trans Golgi network (TGN) where they are sorted from secretory proteins before they are directed to the endosome and then the lysosomes. The sorting events at the TGN involve transmembrane receptors which are themselves bearing sorting determinants in their cytoplasmic tails. The interaction of such sorting signals with adaptor proteins such as APs and GGAs is responsible for the targeting of the receptors (and therefore their cargo). The acidic di Leu signals are interacting with the VHS domains of the GGAs adaptor proteins which in turn can bind to clathrin, ARF factor (regulator of coat assembly at the TGN) and other adaptors interacting with AP-1 gamma subunit. GGAs act by recruiting the receptors into TGN-derived clathrin-coated vesicles for transport to endosomes. The juxtamembrane di Leucine signals interact with AP1, AP2, AP3 and probably AP4 in trafficking events such as endocytosis, targeting to lysosomes or specialed compartments like melanosomes. |
6 selected references:
5 GO-Terms:
16 Instances for TRG_LysEnd_APsAcLL_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement