ELM
The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
«TRG_Golgi_diPhe_1« »TRG_LysEnd_GGAAcLL_2»

TRG_LysEnd_GGAAcLL_1

Accession:
Functional site class:
Trans-Golgi Network-Endosome-Lysosome-sorting signals
Functional site description:
DxxLL acidic dileucine motifs act as sorting signals between the trans-Golgi network (TGN) and the endosomal-lysosomal compartment. Generally found near the protein C-terminus, they interact with GGA proteins which in turn can recruit clathrin.
ELMs with same func. site: TRG_LysEnd_GGAAcLL_1 TRG_LysEnd_GGAAcLL_2
ELM Description:
Sorting signal located at the C-terminus of type I transmembrane proteins from the Trans Golgi Network (TGN) targeted to the lysosomal-endosomal compartment. It interacts with the VHS domain of GGAs adaptor proteins, allowing the incorporation of cargo receptors and their cargo into clathrin coated vesicles budding from the TGN. Phosphorylation of a Serine residue upstream of the motif by casein kinase 2 could regulate the recognition of the motif at the TGN. It has been demonstrated that for the cation dependent mannose 6-phosphate receptor, phosphorylation of this Ser enhances the binding of the signal to its recognition module, the VHS domain of GGAs, by creating an additional point of attcahment to it (Kato,2002).
Pattern: D..LL.{1,2}$
Pattern Probability: 9.585e-07
Present in taxons: Bos taurus Coelomata Gallus gallus Homo sapiens Mus musculus Rattus norvegicus Xenopus laevis
Interaction Domain:
VHS (PF00790) VHS domain (Stochiometry: 1 : 1)
PDB Structure: 1LF8
o See 6 Instances for TRG_LysEnd_GGAAcLL_1
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 trans Golgi network is a major site of membrane protein sorting. The sorting events at the TGN involve transmembrane receptors bearing sorting determinants in their cytoplasmic tails. The interaction of such sorting signals with adaptor proteins such as the GGAs (Golgi-localized, gamma ear-containing, ARF-binding protein) is responsible for the targeting of the receptors (and therefore their cargo). DxxLL acidic diLeucine signals interact with the VHS domains of the GGA adaptor proteins which in turn can bind to clathrin and ARF factor (regulator of coat assembly at the TGN). GGAs act by recruiting the receptors into TGN-derived clathrin-coated vesicles for transport to endosomes. Further sorting to lysosomes or the cell surface may then occur.

The DxxLL acidic diLeucine motifs interacting with GGAs have a very strong preference for Asp at the +1 position. This is in contrast to the acidic diLeucine motifs which bind to the sigma subunit of Adaptin-containing Adapter Protein (AP) complexes also involved in clathrin mediated vesicular transport: The AP complexes have a preference for Glu in the ExxLL acidic dileucine motifs (TRG_DiLeu_BaEn_1).
o 5 selected references:


o 6 GO-Terms:
Biological Process:
Intracellular Protein Transport (also annotated in these classes: LIG_EF_ALG2_ABM_1 LIG_EF_ALG2_ABM_2 TRG_ER_diLys_1 TRG_LysEnd_APsAcLL_1 TRG_LysEnd_APsAcLL_3 TRG_LysEnd_GGAAcLL_2 )
Protein Targeting (also annotated in these classes: TRG_ER_diArg_1 TRG_ER_diLys_1 TRG_ER_KDEL_1 TRG_Golgi_diPhe_1 TRG_LysEnd_APsAcLL_1 TRG_LysEnd_APsAcLL_3 TRG_LysEnd_GGAAcLL_2 )
Cellular Compartment:
Cytosol (also annotated in these classes: CLV_C14_Caspase3-7 CLV_Separin_Fungi CLV_Separin_Metazoa DEG_APCC_DBOX_1 DEG_APCC_KENBOX_2 DEG_APCC_TPR_1 DEG_Cend_DCAF12_1 DEG_Cend_FEM1AC_1 DEG_Cend_FEM1B_2 DEG_Cend_KLHDC2_1 DEG_Cend_TRIM7_1 DEG_COP1_1 DEG_CRBN_cyclicCter_1 DEG_Kelch_actinfilin_1 DEG_Kelch_Keap1_1 DEG_Kelch_Keap1_2 DEG_Kelch_KLHL12_1 DEG_Kelch_KLHL3_1 DEG_MDM2_SWIB_1 DEG_Nend_Nbox_1 DEG_Nend_UBRbox_1 DEG_Nend_UBRbox_2 DEG_Nend_UBRbox_3 DEG_Nend_UBRbox_4 DEG_ODPH_VHL_1 DEG_SCF_FBW7_1 DEG_SCF_FBW7_2 DEG_SCF_FBXO31_1 DEG_SCF_SKP2-CKS1_1 DEG_SCF_TRCP1_1 DEG_SIAH_1 DOC_AGCK_PIF_1 DOC_AGCK_PIF_2 DOC_AGCK_PIF_3 DOC_ANK_TNKS_1 DOC_CDC14_PxL_1 DOC_CKS1_1 DOC_CYCLIN_D_Helix_1 DOC_CYCLIN_RevRxL_6 DOC_CYCLIN_RxL_1 DOC_CYCLIN_yClb1_LxF_4 DOC_CYCLIN_yClb3_PxF_3 DOC_CYCLIN_yCln2_LP_2 DOC_GSK3_Axin_1 DOC_MAPK_DCC_7 DOC_MAPK_FxFP_2 DOC_MAPK_gen_1 DOC_MAPK_GRA24_9 DOC_MAPK_HePTP_8 DOC_MAPK_JIP1_4 DOC_MAPK_MEF2A_6 DOC_MAPK_NFAT4_5 DOC_MAPK_RevD_3 DOC_MIT_MIM_1 DOC_PP1_MyPhoNE_1 DOC_PP1_RVXF_1 DOC_PP1_SILK_1 DOC_PP2A_B56_1 DOC_PP2A_KARD_1 DOC_PP2B_LxvP_1 DOC_PP2B_PxIxIT_1 DOC_PUB_PIM_1 DOC_RSK_DDVF_1 DOC_SPAK_OSR1_1 DOC_TBK1_STING_1 DOC_WD40_RPTOR_TOS_1 DOC_WW_Pin1_4 LIG_14-3-3_CanoR_1 LIG_14-3-3_ChREBP_3 LIG_14-3-3_CterR_2 LIG_ActinCP_CPI_1 LIG_ActinCP_TwfCPI_2 LIG_Actin_RPEL_3 LIG_Actin_WH2_1 LIG_Actin_WH2_2 LIG_ANK_PxLPxL_1 LIG_AP2alpha_1 LIG_AP2alpha_2 LIG_APCC_ABBA_1 LIG_APCC_Cbox_1 LIG_APCC_Cbox_2 LIG_AP_GAE_1 LIG_Arc_Nlobe_1 LIG_ARL_BART_1 LIG_BH_BH3_1 LIG_BIR_II_1 LIG_BIR_III_1 LIG_BIR_III_2 LIG_BIR_III_3 LIG_BIR_III_4 LIG_CaM_1-14-15-16_REV_1 LIG_CaM_1-26_7 LIG_CaM_1-5-10-14_3 LIG_CaM_1-8-14_4 LIG_CaM_1-8-9-10_5 LIG_CaM_1-8_REV_2 LIG_CaM_IQ_9 LIG_CaMK_CASK_1 LIG_CaM_NSCaTE_8 LIG_CAP-Gly_1 LIG_CAP-Gly_2 LIG_Clathr_ClatBox_1 LIG_Clathr_ClatBox_2 LIG_CNOT1_NIM_1 LIG_CSK_EPIYA_1 LIG_CtBP_PxDLS_1 LIG_deltaCOP1_diTrp_1 LIG_DLG_GKlike_1 LIG_Dynein_DLC8_1 LIG_EABR_CEP55_1 LIG_EF_ALG2_ABM_1 LIG_EF_ALG2_ABM_2 LIG_EH_1 LIG_eIF4E_1 LIG_eIF4E_2 LIG_EVH1_1 LIG_EVH1_2 LIG_EVH1_3 LIG_FAT_LD_1 LIG_FERM_MyoX_1 LIG_FZD_DVL_PDZ LIG_G3BP_FGDF_1 LIG_GBD_Chelix_1 LIG_GBD_WASP_1 LIG_GSK3_LRP6_1 LIG_GYF LIG_IBAR_NPY_1 LIG_IRF7_LxLS_2 LIG_IRFs_LxIS_1 LIG_KLC1_WD_1 LIG_KLC1_Yacidic_2 LIG_LIR_Apic_2 LIG_LIR_Gen_1 LIG_LIR_LC3C_4 LIG_LIR_Nem_3 LIG_LYPXL_L_2 LIG_LYPXL_S_1 LIG_LYPXL_yS_3 LIG_MYND_3 LIG_OCRL_FandH_1 LIG_PAM2_1 LIG_PAM2_2 LIG_PDZ_Class_1 LIG_PDZ_Class_2 LIG_PDZ_Class_3 LIG_PDZ_Wminus1_1 LIG_Pex14_1 LIG_Pex14_2 LIG_Pex14_3 LIG_Pex14_4 LIG_Pex3_1 LIG_PIP2_ANTH_1 LIG_PIP2_ENTH_1 LIG_PROFILIN_1 LIG_PTAP_UEV_1 LIG_PTB_Apo_2 LIG_PTB_Phospho_1 LIG_SH2_CRK LIG_SH2_GRB2like LIG_SH2_NCK_1 LIG_SH2_PTP2 LIG_SH2_SFK_2 LIG_SH2_SFK_CTail_3 LIG_SH2_STAT3 LIG_SH2_STAT5 LIG_SH2_STAT6 LIG_SH3_1 LIG_SH3_2 LIG_SH3_3 LIG_SH3_4 LIG_SH3_CIN85_PxpxPR_1 LIG_SH3_PxRPPK_7 LIG_SH3_PxxDY_5 LIG_SH3_PxxPPRxxK_8 LIG_SH3_PxxxRxxKP_6 LIG_SPRY_1 LIG_SUFU_1 LIG_SxIP_EBH_1 LIG_TPR LIG_TRAF2like_MATH_loPxQ_2 LIG_TRAF2like_MATH_shPxQ_1 LIG_TRAF3_MATH_PxP_3 LIG_TRAF4_MATH_1 LIG_TRAF6_MATH_1 LIG_TYR_ITAM LIG_TYR_ITIM LIG_TYR_ITSM LIG_UFM1_UFIM_1 LIG_VCP_SHPBox_1 LIG_VCP_VBM_3 LIG_VCP_VIM_2 LIG_Vh1_VBS_1 LIG_WH1 LIG_WRC_WIRS_1 LIG_WW_1 LIG_WW_2 LIG_WW_3 MOD_AAK1BIKe_LxxQxTG_1 MOD_CAAXbox MOD_CDC14_SPxK_1 MOD_CDK_SPK_2 MOD_CDK_SPxK_1 MOD_CDK_SPxxK_3 MOD_CK1_1 MOD_CK2_1 MOD_DYRK1A_RPxSP_1 MOD_GSK3_1 MOD_LATS_1 MOD_LOK_YxT_1 MOD_NEK2_1 MOD_NEK2_2 MOD_NMyristoyl MOD_PIKK_1 MOD_PK_1 MOD_PKA_1 MOD_PKA_2 MOD_PKB_1 MOD_PLK MOD_Plk_1 MOD_Plk_2-3 MOD_Plk_4 MOD_PRMT_GGRGG_1 MOD_ProDKin_1 MOD_SPalmitoyl_2 MOD_SPalmitoyl_4 MOD_TYR_CSK MOD_TYR_DYR ELM:old_LIG_14-3-3_1 ELM:old_LIG_14-3-3_2 ELM:old_LIG_14-3-3_3 TRG_AP2beta_CARGO_1 TRG_Cilium_Arf4_1 TRG_Cilium_RVxP_2 TRG_DiLeu_BaEn_1 TRG_DiLeu_BaEn_2 TRG_DiLeu_BaEn_3 TRG_DiLeu_BaEn_4 TRG_DiLeu_BaLyEn_6 TRG_DiLeu_LyEn_5 TRG_ENDOCYTIC_2 TRG_ER_diArg_1 TRG_ER_diLys_1 TRG_ER_FFAT_1 TRG_ER_FFAT_2 TRG_Golgi_diPhe_1 TRG_LysEnd_APsAcLL_1 TRG_LysEnd_APsAcLL_3 TRG_LysEnd_GGAAcLL_2 TRG_NES_CRM1_1 TRG_NESrev_CRM1_2 TRG_PTS1 TRG_PTS2 )
Plasma Membrane (also annotated in these classes: DEG_CRBN_cyclicCter_1 DOC_GSK3_Axin_1 LIG_CaM_1-17_6 LIG_CaM_1-26_7 LIG_CaM_1-5-10-14_3 LIG_CaM_1-8-14_4 LIG_CaM_1-8-9-10_5 LIG_CaM_1-8_REV_2 LIG_CaM_NSCaTE_8 LIG_EH_1 LIG_FAT_LD_1 LIG_SH2_SFK_2 LIG_SH2_SFK_CTail_3 LIG_SH2_STAP1 LIG_SH3_1 LIG_SH3_2 LIG_SH3_3 LIG_SH3_PxxDY_5 LIG_WW_1 TRG_Cilium_Arf4_1 TRG_DiLeu_BaEn_1 TRG_DiLeu_BaEn_2 TRG_DiLeu_BaEn_3 TRG_DiLeu_BaEn_4 TRG_DiLeu_BaLyEn_6 TRG_DiLeu_LyEn_5 TRG_ENDOCYTIC_2 TRG_ER_FFAT_1 TRG_ER_FFAT_2 )
Integral Plasma Membrane Protein (also annotated in these classes: LIG_TRAF4_MATH_1 LIG_WW_1 LIG_WW_2 )
Molecular Function:
Protein Binding (also annotated in these classes: CLV_C14_Caspase3-7 CLV_Separin_Fungi CLV_Separin_Metazoa DEG_APCC_TPR_1 DEG_Cend_DCAF12_1 DEG_Cend_FEM1AC_1 DEG_Cend_FEM1B_2 DEG_Cend_KLHDC2_1 DEG_Cend_TRIM7_1 DEG_COP1 DEG_COP1_1 DEG_CRBN_cyclicCter_1 DEG_CRL4_CDT2_1 DEG_CRL4_CDT2_2 DEG_ODPH_VHL_1 DEG_SCF_COI1_1 DEG_SCF_FBW7_1 DEG_SCF_FBW7_2 DEG_SCF_FBXO31_1 DEG_SCF_SKP2-CKS1_1 DEG_SCF_TIR1_1 DEG_SCF_TRCP1_1 DEG_SIAH_1 DOC_AGCK_PIF_1 DOC_AGCK_PIF_2 DOC_AGCK_PIF_3 DOC_ANK_TNKS_1 DOC_CKS1_1 DOC_MAPK_DCC_7 DOC_MAPK_GRA24_9 DOC_MAPK_HePTP_8 DOC_MAPK_JIP1_4 DOC_MAPK_MEF2A_6 DOC_MAPK_NFAT4_5 DOC_PIKK_1 DOC_PP1_MyPhoNE_1 DOC_PP1_RVXF_1 DOC_PP1_SILK_1 DOC_PP2A_B56_1 DOC_PP2A_KARD_1 DOC_PP2B_LxvP_1 DOC_RSK_DDVF_1 DOC_SPAK_OSR1_1 DOC_WD40_RPTOR_TOS_1 LIG_14-3-3_ChREBP_3 LIG_ActinCP_CPI_1 LIG_ActinCP_TwfCPI_2 LIG_ANK_PxLPxL_1 LIG_AP2alpha_1 LIG_AP2alpha_2 LIG_APCC_Cbox_1 LIG_APCC_Cbox_2 LIG_AP_GAE_1 LIG_ARL_BART_1 LIG_ARS2_EDGEI_1 LIG_BH_BH3_1 LIG_BIR_II_1 LIG_BIR_III_1 LIG_BIR_III_2 LIG_BIR_III_3 LIG_BIR_III_4 LIG_CaM_IQ_9 LIG_CaMK_CASK_1 LIG_CNOT1_NIM_1 LIG_deltaCOP1_diTrp_1 LIG_DLG_GKlike_1 LIG_Dynein_DLC8_1 LIG_EABR_CEP55_1 LIG_EF_ALG2_ABM_1 LIG_EF_ALG2_ABM_2 LIG_EH_1 LIG_eIF4E_1 LIG_eIF4E_2 LIG_EVH1_1 LIG_EVH1_2 LIG_FAT_LD_1 LIG_FHA_1 LIG_FHA_2 LIG_FXI_DFP_1 LIG_GLEBS_BUB3_1 LIG_HCF-1_HBM_1 LIG_IBAR_NPY_1 LIG_Integrin_isoDGR_2 LIG_IRF7_LxLS_2 LIG_IRFs_LxIS_1 LIG_KLC1_Yacidic_2 LIG_LEDGF_IBM_1 LIG_LIR_Apic_2 LIG_LIR_Gen_1 LIG_LIR_LC3C_4 LIG_LIR_Nem_3 LIG_LRP6_Inhibitor_1 LIG_LSD1_SNAG_1 LIG_LYPXL_L_2 LIG_LYPXL_S_1 LIG_LYPXL_SIV_4 LIG_LYPXL_yS_3 LIG_MAD2 LIG_Menin_MBM1_1 LIG_MLH1_MIPbox_1 LIG_MSH2_SHIPbox_1 LIG_MTR4_AIM_1 LIG_Mtr4_Air2_1 LIG_Mtr4_Trf4_1 LIG_Mtr4_Trf4_2 LIG_MYND_3 LIG_Nrd1CID_NIM_1 LIG_NRP_CendR_1 LIG_OCRL_FandH_1 LIG_PALB2_WD40_1 LIG_PDZ_Class_1 LIG_PDZ_Class_2 LIG_PDZ_Class_3 LIG_PDZ_Wminus1_1 LIG_Pex14_1 LIG_Pex14_2 LIG_Pex3_1 LIG_PTB_Apo_2 LIG_PTB_Phospho_1 LIG_RBL1_LxSxE_2 LIG_RB_pABgroove_1 LIG_REV1ctd_RIR_1 LIG_RPA_C_Plants LIG_RPA_C_Vert LIG_RuBisCO_WRxxL_1 LIG_SH2_CRK LIG_SH2_GRB2like LIG_SH2_NCK_1 LIG_SH2_SFK_2 LIG_SH2_SFK_CTail_3 LIG_SH2_STAP1 LIG_SH3_1 LIG_SH3_2 LIG_SH3_3 LIG_SH3_4 LIG_SH3_CIN85_PxpxPR_1 LIG_SH3_PxxDY_5 LIG_SPRY_1 LIG_SUFU_1 LIG_TRAF2like_MATH_loPxQ_2 LIG_TRAF2like_MATH_shPxQ_1 LIG_TRAF3_MATH_PxP_3 LIG_TRAF4_MATH_1 LIG_TRAF6_MATH_1 LIG_Trf4_IWRxY_1 LIG_UFM1_UFIM_1 LIG_VCP_SHPBox_1 LIG_VCP_VBM_3 LIG_VCP_VIM_2 LIG_Vh1_VBS_1 LIG_WD40_WDR5_VDV_1 LIG_WD40_WDR5_VDV_2 LIG_WD40_WDR5_WIN_1 LIG_WD40_WDR5_WIN_2 LIG_WD40_WDR5_WIN_3 LIG_WH1 LIG_WRC_WIRS_1 LIG_WW_1 LIG_WW_2 LIG_WW_3 MOD_Plk_2-3 MOD_Plk_4 MOD_PRMT_GGRGG_1 TRG_AP2beta_CARGO_1 TRG_Cilium_Arf4_1 TRG_Cilium_RVxP_2 TRG_DiLeu_BaEn_1 TRG_DiLeu_BaEn_2 TRG_DiLeu_BaEn_3 TRG_DiLeu_BaEn_4 TRG_DiLeu_BaLyEn_6 TRG_DiLeu_LyEn_5 TRG_ER_diLys_1 TRG_ER_FFAT_1 TRG_ER_FFAT_2 TRG_Golgi_diPhe_1 TRG_LysEnd_APsAcLL_1 TRG_LysEnd_APsAcLL_3 TRG_LysEnd_GGAAcLL_2 TRG_NES_CRM1_1 TRG_NESrev_CRM1_2 TRG_NLS_Bipartite_1 TRG_NLS_MonoCore_2 TRG_NLS_MonoExtC_3 TRG_NLS_MonoExtN_4 )


Please cite: ELM-the Eukaryotic Linear Motif resource-2024 update. (PMID:37962385)

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