ELM
The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
«LIG_TRAF6_MATH_1« »LIG_TRFH_1»

LIG_Trf4_IWRxY_1

Accession:
Functional site class:
Trf4 PAP-associated domain ligand
Functional site description:
The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) RNA quality control complex is a key player in RNA surveillance. Within this complex Air1/2 employs its 5th zinc knuckle and a conserved IWRxY motif within the linker connecting the 4th and 5th zinc knuckles for binding Trf4, while other regions of the protein (including an MTR4 arch domain-interacting (AIM) motif) contact Mtr4, thus ultimately fulfilling a bridging function within the complex. The motif is present in the close paralogs Air1 and Air2 and it seems to be strictly conserved from yeasts to human, since it is also present in the human ortholog ZCCHC7.
ELM Description:
The IWRxY motif is located at the beginning of the linker between the 4th and 5th zinc knuckles of Air1/2, right after the 4th zinc knuckle (Fasken,2011; Hamill,2010). The conserved starting Ile residue of the motif is only separated by two residues from the last Cys of the 4th zinc knuckle. This is probably the reason why, although the motif resides within a linker, it is not predicted to be natively disordered.
In the complex (3NYB) between yeast Air2 (Q12476) and Trf4 (P53632) the motif is partly helical, a helix is formed by part of the 4th zinc knuckle, the residues separating it from the motif and the first two residues of the motif I139 and the conserved W140 (UniProt numbering). W140 fits into a hydrophobic pocket, while the first residue after the helix, R141 coordinates several salt bridges with both E378 and E381 of Trf4. With the following residue, A142, the Air2 chain turns back and the following conserved Y143 forms a hydrogen bond with the sidechain of E378 of Trf4 through its OH group (so a change to Phe in this position would destroy this contact; Hamill,2010). L145 also makes hydrophobic contacts and it is highly conserved in yeasts and in vertebrates, except for S. pombe Air1. The structural features of the bound motif are in good agreement with the alignments of Air1 and Air2 showing that while the I139 position has slight sequence variability among similarly sized hydrophobic residues Ile, Leu and Val, the W140, R141 and Y143 positions are strictly conserved in all the species.

Pattern: [IVL]WR.Y
Pattern Probability: 8.990e-07
Present in taxon: Eukaryota
Interaction Domain:
PAP/25A-associated (IPR002058) This domain is found in poly(A) polymerases and has been shown to have polynucleotide adenylyltransferase activity (Stochiometry: 1 : 1)
o See 4 Instances for LIG_Trf4_IWRxY_1
o Abstract
The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex is a major player in RNA surveillance and decay pathways. The TRAMP complex can be considered as a nuclear exosome cofactor that recruits the exosome to degrade certain unwanted RNA species (Fasken,2011).

Within the complex, the RNA-binding protein Air1/2 performs a bridging function between the poly(A) polymerase (Trf4/5) and RNA helicase (Mtr4) subunits (Holub,2012). Air1/2 interacts with Trf4 through its 4th and 5th zinc knuckles and a conserved IWRxY motif at the beginning of the linker connecting them (Fasken,2011; Holub,2012), while other regions of the protein (including an N-terminal MTR4 arch domain-interacting (AIM) motif LIG_MTR4_AIM_1) contact Mtr4 (Falk,2014). The motif is present in the close paralogs Air1 and Air2 and it seems to be strictly conserved from yeasts to human, as it is also present in the human ortholog ZCCHC7 that is known to interact with PAPD5 and PAPD7, the human orthologs of Trf4 (Fasken,2011). Human TRAMP-like proteins are involved in the turnover of pre-rRNA 5'ETS fragments (Sudo,2016). In S. pombe there is a single TRAMP-like complex that consists of Mtr4, Cid14, and Air1 (Keller,2010).

The Trf4p surface bound by the Air2 motif and zinc knuckle is highly conserved in a wide range of eukaryotes (Hamill,2010). There is a structure available for the complex (3NYB) between yeast Air2 (Q12476) and Trf4 (P53632) which justifies the high conservation of the IWRxY residues, since they mediate various contacts with Trf4 (Hamill,2010). The full interaction surface with Trf4 is considerably larger than the motif interface. While the 4th zinc knuckle (residues 123–136) is only tethered to Trf4p via the adjacent motif and has little direct contact with Trf4p, the 5th zinc knuckle makes an extensive interaction. The motif and the 5th knuckle are separated by a flexible linker not visible in the structure (Hamill,2010). Mutations to Zn knuckles 4 or 5 or the IWRxY motif in Air1 or 2 cause temperature-sensitive growth defects in S. cerevisiae, most probably through compromising the integrity of the TRAMP complex (Fasken,2011; Holub,2012).
o 4 selected references:


o 12 GO-Terms:
Biological Process:
Mrna Processing (also annotated in these classes: LIG_ARS2_EDGEI_1 LIG_MTR4_AIM_1 )
Nuclear Rna Surveillance (also annotated in these classes: LIG_ARS2_EDGEI_1 LIG_MTR4_AIM_1 LIG_Mtr4_Air2_1 LIG_Mtr4_Trf4_1 LIG_Mtr4_Trf4_2 LIG_Nrd1CID_NIM_1 )
Regulation Of Mrna Catabolic Process (also annotated in these classes: LIG_ARS2_EDGEI_1 LIG_MTR4_AIM_1 )
Rrna Processing (also annotated in these classes: LIG_MTR4_AIM_1 )
Snrna Catabolic Process (also annotated in these classes: LIG_MTR4_AIM_1 )
Rna Catabolic Process (also annotated in these classes: LIG_MTR4_AIM_1 )
Cellular Compartment:
Nucleolus (also annotated in these classes: DOC_CDC14_PxL_1 LIG_Mtr4_Air2_1 LIG_Mtr4_Trf4_1 LIG_Mtr4_Trf4_2 LIG_Nrd1CID_NIM_1 MOD_CDC14_SPxK_1 MOD_Plk_2-3 )
Protein-Containing Complex (also annotated in these classes: LIG_ARS2_EDGEI_1 LIG_MSH2_SHIPbox_1 LIG_MTR4_AIM_1 LIG_WRC_WIRS_1 )
Tramp Complex (also annotated in these classes: LIG_MTR4_AIM_1 LIG_Mtr4_Air2_1 LIG_Mtr4_Trf4_1 LIG_Mtr4_Trf4_2 LIG_Nrd1CID_NIM_1 LIG_Rrp6Rrp47_Mtr4_1 )
Nucleus (also annotated in these classes: CLV_C14_Caspase3-7 CLV_Separin_Fungi CLV_Separin_Metazoa CLV_TASPASE1 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 DEG_COP1_1 DEG_CRL4_CDT2_1 DEG_CRL4_CDT2_2 DEG_Kelch_Keap1_1 DEG_Kelch_Keap1_2 DEG_MDM2_SWIB_1 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 DEG_SPOP_SBC_1 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_yClb5_NLxxxL_5 DOC_CYCLIN_yCln2_LP_2 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_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_PP2B_PxIxIT_1 DOC_PP4_FxxP_1 DOC_PP4_MxPP_1 DOC_USP7_MATH_1 DOC_USP7_MATH_2 DOC_USP7_UBL2_3 DOC_WW_Pin1_4 LIG_14-3-3_CanoR_1 LIG_14-3-3_ChREBP_3 LIG_14-3-3_CterR_2 LIG_ANK_PxLPxL_1 LIG_APCC_ABBA_1 LIG_APCC_Cbox_1 LIG_APCC_Cbox_2 LIG_ARL_BART_1 LIG_ARS2_EDGEI_1 LIG_BRCT_BRCA1_1 LIG_BRCT_BRCA1_2 LIG_BRCT_MDC1_1 LIG_CaM_1-14-15-16_REV_1 LIG_CaMK_CASK_1 LIG_CORNRBOX LIG_CSL_BTD_1 LIG_CtBP_PxDLS_1 LIG_CtBP_RRT_2 LIG_DCNL_PONY_1 LIG_EF_ALG2_ABM_1 LIG_EF_ALG2_ABM_2 LIG_EH1_1 LIG_FHA_1 LIG_FHA_2 LIG_GLEBS_BUB3_1 LIG_HCF-1_HBM_1 LIG_HOMEOBOX LIG_HP1_1 LIG_IRF7_LxLS_2 LIG_IRFs_LxIS_1 LIG_KEPE_1 LIG_KEPE_2 LIG_KEPE_3 LIG_LEDGF_IBM_1 LIG_LSD1_SNAG_1 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_1 LIG_MYND_2 LIG_MYND_3 LIG_NBox_RRM_1 LIG_NRBOX LIG_Nrd1CID_NIM_1 LIG_PALB2_WD40_1 LIG_PCNA_APIM_2 LIG_PCNA_PIPBox_1 LIG_PCNA_TLS_4 LIG_PCNA_yPIPBox_3 LIG_PTAP_UEV_1 LIG_RBL1_LxSxE_2 LIG_RB_LxCxE_1 LIG_RB_pABgroove_1 LIG_REV1ctd_RIR_1 LIG_RPA_C_Plants LIG_RPA_C_Vert LIG_RRM_PRI_1 LIG_Rrp6Rrp47_Mtr4_1 LIG_Sin3_1 LIG_Sin3_2 LIG_Sin3_3 LIG_SUFU_1 LIG_SUMO_SIM_anti_2 LIG_SUMO_SIM_par_1 LIG_TPR LIG_TRFH_1 LIG_UBA3_1 LIG_ULM_U2AF65_1 LIG_VCP_SHPBox_1 LIG_VCP_VBM_3 LIG_VCP_VIM_2 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_WRPW_1 LIG_WRPW_2 LIG_WW_2 MOD_AAK1BIKe_LxxQxTG_1 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_NEK2_1 MOD_NEK2_2 MOD_PIKK_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_SUMO_for_1 MOD_SUMO_rev_2 ELM:old_LIG_14-3-3_1 ELM:old_LIG_14-3-3_2 ELM:old_LIG_14-3-3_3 TRG_NES_CRM1_1 TRG_NESrev_CRM1_2 TRG_NLS_Bipartite_1 TRG_NLS_MonoCore_2 TRG_NLS_MonoExtC_3 TRG_NLS_MonoExtN_4 )
Molecular Function:
Protein Domain Specific Binding (also annotated in these classes: DEG_APCC_DBOX_1 DEG_APCC_KENBOX_2 DEG_Cend_DCAF12_1 DEG_Cend_FEM1AC_1 DEG_Cend_FEM1B_2 DEG_Cend_KLHDC2_1 DEG_Cend_TRIM7_1 DEG_Kelch_actinfilin_1 DEG_Kelch_Keap1_1 DEG_Kelch_Keap1_2 DEG_Kelch_KLHL3_1 DOC_MIT_MIM_1 LIG_14-3-3_CanoR_1 LIG_14-3-3_CterR_2 LIG_AP_GAE_1 LIG_ARS2_EDGEI_1 LIG_BRCT_BRCA1_1 LIG_BRCT_BRCA1_2 LIG_BRCT_MDC1_1 LIG_CAP-Gly_1 LIG_CSK_EPIYA_1 LIG_CSL_BTD_1 LIG_deltaCOP1_diTrp_1 LIG_EH_1 LIG_EVH1_1 LIG_EVH1_2 LIG_EVH1_3 LIG_FHA_1 LIG_FHA_2 LIG_G3BP_FGDF_1 LIG_MSH2_SHIPbox_1 LIG_MTR4_AIM_1 LIG_PAM2_1 LIG_PAM2_2 LIG_PDZ_Class_1 LIG_PDZ_Class_2 LIG_PDZ_Class_3 LIG_PDZ_Wminus1_1 LIG_PTB_Apo_2 LIG_PTB_Phospho_1 LIG_RRM_PRI_1 LIG_SH3_1 LIG_SH3_2 LIG_SH3_3 LIG_SH3_4 LIG_SH3_PxRPPK_7 LIG_SH3_PxxDY_5 LIG_SH3_PxxPPRxxK_8 LIG_SH3_PxxxRxxKP_6 LIG_TRFH_1 LIG_ULM_U2AF65_1 LIG_WH1 ELM:old_LIG_14-3-3_1 ELM:old_LIG_14-3-3_2 ELM:old_LIG_14-3-3_3 )
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_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_1 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)

ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement

AltStyle によって変換されたページ (->オリジナル) /