The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
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:
Based on in vitro experiments (see references) this much more restricted pattern has been described for di-Leucine motifs interacting with the AP3 adaptor complex. It is found in a subset of proteins targeted to melanosomes, endosomes and lysosomes.
Pattern: [DET]E[RK].PL[LI]
Pattern Probability: 0.0000015
Present in taxon: Vertebrata
Interaction Domain:
Clat_adaptor_s (PF01217) Clathrin adaptor complex small chain (Stochiometry: 1 : 1)
o See 3 Instances for TRG_LysEnd_APsAcLL_3
o 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.
o 4 selected references:

o 5 GO-Terms:

o 3 Instances for TRG_LysEnd_APsAcLL_3
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q90372 QNR-71
546 552 FFFPKSTERNPLLKSKPGIV TP 6 Coturnix japonica (Japanese quail)
P11344 Tyr
512 518 KKKQPQEERQPLLMDKDDYH TP 2 Mus musculus (House mouse)
Q14108 SCARB2
470 476 KGQGSMDEGTADERAPLIRT TP 10 Homo sapiens (Human)
Please cite: ELM — the eukaryotic linear motif resource in 2020. (PMID:31680160)

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