The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
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
o Abstract
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:

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
303 306 LFRDSPAGDHDYALPVGKQK TP 4 Homo sapiens (Human)
76 79 FSQLSLHNDHPYCSPPMTFS TP 3 Homo sapiens (Human)
Q16254 E2F4
389 392 LRLSPPPGDHDYIYNLDESE TP 2 Homo sapiens (Human)
P29747 CrebA
64 67 NGTQPIKTEHSYSLSSDVDS TP 4 Drosophila melanogaster (Fruit fly)
Q9JJD0 Thap11
234 237 EGFPDTGSDHSYSLSSGTTE TP 2 Mus musculus (House mouse)
134 137 PVNLSVFCDHNYTVEDTMHQ TP 3 Homo sapiens (Human)
321 324 YGTEVLQIEHSYCRQDINKE TP 1 Homo sapiens (Human)
1295 1298 SRVHVGSGDHDYCVRSRTPP TP 2 Homo sapiens (Human)
P08152 Egr2
162 165 MSQTQPELDHLYSPPPPPPP TP 1 Mus musculus (House mouse)
177 180 RTPNKQPSDHSYALLDLDSL TP 4 Homo sapiens (Human)
123 126 ISSQQVLLEHSYAFRNPMEA TP 1 Homo sapiens (Human)
139 142 EFQSQFIFEHSYSVMDSPKK TP 1 Homo sapiens (Human)
123 126 NSQEVATEDHNYSLKTPLTI TP 1 Homo sapiens (Human)
P06492 UL48
361 364 SPSEAVMREHAYSRARTKNN TP 1 Herpes simplex virus (type 1 / strain 17)
229 232 PAGAYIQNEHSYQVGSALLW TP 1 Homo sapiens (Human)
Q01094 E2F1
97 100 KRRLDLETDHQYLAESSGPA TP 3 Homo sapiens (Human)
O43889 CREB3
78 81 SNPCLVHHDHTYSLPRETVS TP 4 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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