ELM
The Eukaryotic Linear Motif resource for
Functional Sites in Proteins

LIG_HCF-1_HBM_1

Accession:
Functional site class:
HCF-1 binding motif
Functional site description:
The Host Cell Factor-1 (HCF-1) is a transcriptional co-activator involved in a number of important gene regulatory complexes. HCF-1 is a chromatin associated protein and it interacts with a wide variety of cellular factors including co-activators and co-repressors that function in cell growth and cell division. It is conserved from human to nematodes. HCF-1 contains several domains that mediate specific interaction with different binding partners. In particular the N-terminal region contains six kelch repeats that fold into a six-bladed propeller domain. This propeller region is sufficient to target a number of interacting proteins by recognizing a conserved DHxY peptide sequence known as the HCF-1 binding motif (HBM).
ELM Description:
The HBM is a short well-conserved sequence motif matching [ED]HxY. (A reported exception is an NHNY in BAP1 but, as this is an isolated outlier, it has not been included in the current ELM regular expression.) The motif is typically found in transcriptional regulators that affect cell cycle. HBM belongs to the common category of beta propeller-binding motifs. Although there is not yet a solved structure for the HBM in complex with the kelch repeat propeller, the evidence for the interaction is strong and the motif description appears convincing, based on strong motif conservation in multiple protein families.
Pattern: [DE]H.Y
Pattern Probability: 0.0000507
Present in taxon: Metazoa
Interaction Domain:
Kelch_3 (PF13415) Galactose oxidase, central domain (Stochiometry: 4 : 1)
o See 17 Instances for LIG_HCF-1_HBM_1
HCF-1, the metazoan host cell factor-1 is a conserved cellular transcription factor also called VCAF1, C1, or CCF. This protein became of interest as an accessory protein required for the lytic mode of herpes simplex virus infection in association with the virion protein VP16 (Wysocka,2003; Kristie,2010). HCF-1 is exclusively nuclear and expressed in almost all mammalian cell types (Ajuh,2002). The homologues of HCF-1 are present both in vertebrates and invertebrates but with sufficient divergence that the lineages may have somewhat different functions. The association of HCF-1 with several transcription factors showed the possible role for the protein in gene transcription (Lu,1997; Lu,1998; Lu,2000). In addition HCF-1 may play an important role in spliceosome assembly and pre-mRNA splicing in mammals (Ajuh,2002), cell proliferation (Freiman,1997; Machida,2009) and cell cycle progression (Wysocka,2001). Interactions with several E2F factors are strong indications of the importance of HCF-1 for cell cycle regulation (Tyagi,2007).
The human HCF-1 polypeptide is synthesized as a large precursor that is subsequently cleaved at specific repeats located towards the centre of the protein that are specific targets of proteolysis. After cleavage the resulting family of polypeptides remain bound together through the action of two pairs of self association sequences, SAS1 and SAS2 (Wilson,2000). HCF-1 possesses several distinct polypeptide regions. The N-terminal region contains a Kelch domain consisting of six Kelch repeats, which are predicted to form a beta-propeller structure of linked beta sheets. The C-terminal region of HCF-1 encompasses two Fibronectin type III repeats. A classical bipartite nuclear localization signal (NLS), which is necessary for the nuclear localization of the protein, is located at the extreme C-terminus, just downstream of the FnIII repeats. HCF-1N is essential for G1 phase progression, whereas HCF-1C is important for proper cytokinesis. A number of transcriptional regulatory proteins contain a [DE]HxY motif designated the HCF-1 binding motif (HBM). The HBM interacts with the kelch domain, aiding recruitment of HCF-1 to the promoters it regulates. HBM-containing proteins include transcription factors such as E2Fs, Krox20, CREB3 as well as histone methyltransferases such as MLL and SET1A. The HCV transcriptional regulatory protein VP16 also contains the HBM motif and such usage may be more widespread for viral hijack of the cell cycle.
o 14 selected references:


o 9 GO-Terms:
Biological Process:
Positive Regulation Of Cell Proliferation (also annotated in these classes: DEG_COP1_1 LIG_RB_pABgroove_1 LIG_SH2_GRB2like LIG_TRAF4_MATH_1 )
Regulation Of Cell Cycle (also annotated in these classes: LIG_14-3-3_CanoR_1 LIG_14-3-3_CterR_2 LIG_RBL1_LxSxE_2 LIG_RB_LxCxE_1 LIG_RB_pABgroove_1 MOD_CDK_SPK_2 MOD_CDK_SPxxK_3 MOD_Plk_1 )
Virus-Host Interaction (also annotated in these classes: LIG_BH_BH3_1 LIG_RB_pABgroove_1 )
Regulation Of Transcription (also annotated in these classes: DEG_COP1 LIG_CORNRBOX LIG_NRBOX LIG_RB_pABgroove_1 LIG_WRPW_1 )
Cellular Compartment:
Transcription Factor Complex (also annotated in these classes: DOC_MAPK_DCC_7 DOC_MAPK_MEF2A_6 LIG_CSL_BTD_1 LIG_Menin_MBM1_1 LIG_RB_pABgroove_1 )
Viral Tegument (also annotated in class: )
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_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_Trf4_IWRxY_1 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:
Transcription Factor (also annotated in these classes: LIG_CSL_BTD_1 LIG_NBox_RRM_1 LIG_RB_LxCxE_1 )
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_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_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 )


o 17 Instances for LIG_HCF-1_HBM_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q5VV67 PPRC1
PPRC1_HUMAN
1295 1298 SRVHVGSGDHDYCVRSRTPP TP 2 Homo sapiens (Human)
4
Q9H5L6 THAP9
THAP9_HUMAN
123 126 NSQEVATEDHNYSLKTPLTI TP 1 Homo sapiens (Human)
Q9BT49 THAP7
THAP7_HUMAN
229 232 PAGAYIQNEHSYQVGSALLW TP 1 Homo sapiens (Human)
Q8TBB0 THAP6
THAP6_HUMAN
139 142 EFQSQFIFEHSYSVMDSPKK TP 1 Homo sapiens (Human)
Q7Z6K1 THAP5
THAP5_HUMAN
321 324 YGTEVLQIEHSYCRQDINKE TP 1 Homo sapiens (Human)
Q9H0W7 THAP2
THAP2_HUMAN
123 126 ISSQQVLLEHSYAFRNPMEA TP 1 Homo sapiens (Human)
Q9NVV9 THAP1
THAP1_HUMAN
134 137 PVNLSVFCDHNYTVEDTMHQ TP 4 Homo sapiens (Human)
4
Q8WTV1 THAP3
THAP3_HUMAN
177 180 RTPNKQPSDHSYALLDLDSL TP 5 Homo sapiens (Human)
4
Q9JJD0 Thap11
THA11_MOUSE
234 237 EGFPDTGSDHSYSLSSGTTE TP 2 Mus musculus (House mouse)
4
P08152 Egr2
EGR2_MOUSE
162 165 MSQTQPELDHLYSPPPPPPP TP 1 Mus musculus (House mouse)
4
P29747 CrebA
CREBA_DROME
64 67 NGTQPIKTEHSYSLSSDVDS TP 5 Drosophila melanogaster (Fruit fly)
4
O43889 CREB3
CREB3_HUMAN
78 81 SNPCLVHHDHTYSLPRETVS TP 5 Homo sapiens (Human)
4
Q16254 E2F4
E2F4_HUMAN
389 392 LRLSPPPGDHDYIYNLDESE TP 2 Homo sapiens (Human)
4
Q9NWW0 HCFC1R1
HPIP_HUMAN
76 79 FSQLSLHNDHPYCSPPMTFS TP 3 Homo sapiens (Human)
4
Q9NS37 CREBZF
ZHANG_HUMAN
303 306 LFRDSPAGDHDYALPVGKQK TP 5 Homo sapiens (Human)
4
P06492 UL48
VP16_HHV11
361 364 SPSEAVMREHAYSRARTKNN TP 1 Herpes simplex virus (type 1 / strain 17)
4
Q01094 E2F1
E2F1_HUMAN
97 100 KRRLDLETDHQYLAESSGPA TP 3 Homo sapiens (Human)
4
Please cite: ELM-the Eukaryotic Linear Motif resource-2024 update. (PMID:37962385)

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