TRG_ENDOCYTIC_2

Accession:	ELME000120
Functional site class:	Y-based sorting signal
Functional site description:	Yxxphi sorting signal responsible for the interaction with mu subunit of AP (Adaptor Protein) complex
ELM Description:	Tyrosine-based sorting signal responsible for the interaction with mu subunit of AP (Adaptor Protein) complex
Pattern:	`Y..[LMVIF]`
Pattern Probability:	`0.0025875`
Present in taxons:	Eukaryota Homo sapiens Mus musculus Rattus norvegicus Saccharomyces cerevisiae
Interaction Domain:	Adap_comp_sub (PF00928) Adaptor complexes medium subunit family (Stochiometry: 1 : 1) PDB Structure: 1BXX

o See 15 Instances for TRG_ENDOCYTIC_2

o Abstract

Intracellular traffic of many membrane-bound proteins requires sequences facing the cytoplasm. In many instances the sorting information is encoded in short peptide motifs, typically 4-6 amino acids, which are referred to as sorting signals. These motifs determine which vescicular traffic pathway is used to transport a particular molecule and hence determine its final destination. The Yxxphi motif is a sorting signal found in the cytosolic tail of various membrane proteins as an endocytic motif and also directs traffic within the endosomal and the secretory pathways. The Yxxphi motif interacts with mu subunit of AP (Adaptor Protein) complex.

o 9 selected references:

Endocytosis and lysosomal targeting of epidermal growth factor receptors are mediated by distinct sequences independent of the tyrosine kinase domain.
Opresko LK, Chang CP, Will BH, Burke PM, Gill GN, Wiley HS
J Biol Chem 1995 Mar 3; 270 (9), 4325-33
PMID: 7876194
Recognition of sorting signals by clathrin adaptors.
Heilker R, Spiess M, Crottet P
Bioessays 1999 Jul; 21 (7), 558-67
PMID: 10472183
Recycling of furin from the plasma membrane. Functional importance of the cytoplasmic tail sorting signals and interaction with the AP-2 adaptor medium chain subunit.
Teuchert M, Berghofer S, Klenk HD, Garten W
J Biol Chem 1999 Dec 17; 274 (51), 36781-9
PMID: 10593987
Adaptors for clathrin-mediated traffic.
Kirchhausen T
Annu Rev Cell Dev Biol 1999; 15, 705-32
PMID: 10611976
The molecular machinery for lysosome biogenesis.
Mullins C, Bonifacino JS
Bioessays 2001 Apr; 23 (4), 333-43
PMID: 11268039
Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain.
Kawakami K, Takeshita F, Puri RK
J Biol Chem 2001 Jul 6; 276 (27), 25114-20
PMID: 11352909
Intracellular cycling of lysosomal enzyme receptors: cytoplasmic tails' tales.
Dell'Angelica EC, Payne GS
Cell 2001 Aug 24; 106 (4), 395-8
PMID: 11525725
Accessory protein recruitment motifs in clathrin-mediated endocytosis.
Brett TJ, Traub LM, Fremont DH
Structure (Camb) 2002 Jun; 10 (6), 797-809
PMID: 12057195
The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppO sorting signals at distinct sites.
Boll W, Rapoport I, Brunner C, Modis Y, Prehn S, Kirchhausen T
Traffic 2002 Aug; 3 (8), 590-600
PMID: 12121421

o 7 GO-Terms:

Biological Process:
Endocytosis (also annotated in these classes: LIG_AP2alpha_1 LIG_AP2alpha_2 LIG_Clathr_ClatBox_1 LIG_Clathr_ClatBox_2 LIG_EH_1 LIG_PIP2_ANTH_1 LIG_PIP2_ENTH_1 LIG_SH3_CIN85_PxpxPR_1 MOD_AAK1BIKe_LxxQxTG_1 TRG_AP2beta_CARGO_1 )
Receptor Mediated Endocytosis (also annotated in these classes: LIG_AP2alpha_1 LIG_AP2alpha_2 LIG_Clathr_ClatBox_1 LIG_Clathr_ClatBox_2 LIG_EH_1 LIG_NRP_CendR_1 LIG_PIP2_ANTH_1 )
Cellular Compartment:
Clathrin-Coated Endocytic Vesicle (also annotated in these classes: LIG_AP2alpha_1 LIG_AP2alpha_2 LIG_Clathr_ClatBox_1 LIG_Clathr_ClatBox_2 )
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_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_1 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_ER_FFAT_1 TRG_ER_FFAT_2 TRG_LysEnd_GGAAcLL_1 )
Molecular Function:
Internalization Receptor (also annotated in these classes: LIG_AP2alpha_1 )
Transmembrane Receptor Protein Tyrosine Kinase Adaptor Protein (also annotated in these classes: LIG_AP2alpha_1 )

o 15 Instances for TRG_ENDOCYTIC_2
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)

Acc., Gene-, Name	Start	End	Subsequence	Logic	#Ev.	Organism	Notes
P03522 G VGLG_VSIVA	501	504	LKHTKKRQIYTDIEMNRLGK	U	1	Vesicular stomatitis Indiana virus strain San Juan	1
Q9J3M8 gE GE_VZVO	582	585	SPYNQSMYYAGLPVDDFEDS	TP	4	Human herpesvirus 3 strain Oka vaccine	1
P05884 env ENV_SIVMK	723	726	MLAKLRQGYRPVFSSPPSYF	TP	2	Simian immunodeficiency virus - mac K6W	1
P04578 env ENV_HV1H2	712	715	IVNRVRQGYSPLSFQTHLPT	TP	6	HIV-1 M:B_HXB2R	1
P03383 env ENV_HTLV2	477	480	PQRLQNRHNQYSLINPETML	TP	2	Human T-lymphotropic virus 2	1
P51519 env ENV_BLV	487	490	FPPKPDSDYQALLPSAPEIY	U	1	Bovine leukemia virus	1
P11117 ACP2 PPAL_HUMAN	413	416	FRMQAQPPGYRHVADGEDHA	TP	5	Homo sapiens (Human)	1
P09793 Ctla4 CTLA4_MOUSE	201	204	RSPLTTGVYVKMPPTEPECE	TP	4	Mus musculus (House mouse)	1
P02786 TFRC TFR1_HUMAN	20	23	LFGGEPLSYTRFSLARQVDG	TP	1	Homo sapiens (Human)	1
P19814 Ttgn1 TGON3_RAT	350	353	RSKVTRRPKASDYQRLNLKL	TP	1	Rattus norvegicus (Norway rat)	1BXX 1BXX 1
P16410 CTLA4 CTLA4_HUMAN	201	204	RSPLTTGVYVKMPPTEPECE	TP	0	Homo sapiens (Human)	1
P00533 EGFR EGFR_HUMAN	998	1001	PSPTDSNFYRALMDEEDMDD	TP	0	Homo sapiens (Human)	1
P07306 ASGR1 ASGR1_HUMAN	5	8	MTKEYQDLQHLDNEESDHHQ	TP	0	Homo sapiens (Human)	1
P32004 L1CAM L1CAM_HUMAN	1176	1179	MKDETFGEYRSLESDNEEKA	TP	0	Homo sapiens (Human)	4
P11279 LAMP1 LAMP1_HUMAN	414	417	IVLIAYLVGRKRSHAGYQTI	TP	0	Homo sapiens (Human)	1

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

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