The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
FHA phosphopeptide ligands
Functional site description:
The FHA domain is a signal transduction module which recognizes phosphothreonine containing peptides on the ligand proteins. FHA domains partake in many signalling processes but are especially prevalent in nuclear proteins that are involved in cell cycle checkpoint, DNA repair and transcriptional regulation.
ELMs with same func. site: LIG_FHA_1  LIG_FHA_2 
ELM Description:
LIG_FHA_1 motifs are short phosphothreonine modules binding FHA domains with large aliphatic amino acids at the pT+3 position. The motif has the consensus sequence of T..[IVL]. Proteins with FHA domains having this preference include the checkpoint kinase chk2 (Li,2002) and DNA repair protein rad9 (Byeon,2001).
Pattern: ..(T)..[ILV].
Pattern Probability: 0.0086622
Present in taxon: Eukaryota
Interaction Domain:
FHA (PF00498) FHA domain (Stochiometry: 1 : 1)
PDB Structure: 1K2N
o See 6 Instances for LIG_FHA_1
o Abstract
The forkhead-associated FHA domain is a phosphopeptide-binding domain first identified in a group of forkhead transcription factors (Hofmann,1995). FHA are small domains (<100 amino acids) that form a sandwich of two anti-parallel beta sheets. They are present in a wide variety of proteins from both prokaryotes and eukaryotes (Li,2000). The existence of FHA domains in a wide variety of proteins means they are involved in diverse cellular functions including signal transduction and vesicular transport. In plants, FHA domains participate in the regulation of receptor-like protein kinase signalling pathways (Lee,2003). There are many nuclear FHA-domain containing proteins: these have a variety of roles involved in cell-cycle checkpoint control, DNA repair, signal transduction, transcriptional regulation, and pre-mRNA splicing. Some of the FHA domain-containing proteins are present in the plasma membrane. While FHAs bind to phosphothreonine motifs, BRCT domains recognize phosphoserine motifs in otherwise similar nuclear regulatory contexts. Although weak in vitro binding of phosphoserine and phosphotyrosine peptides has been observed, all high affinity interactions utilize phosphothreonine, which may be an essential requirement for the biological ligands. The optimal FHA domain binding sequence is a phosphothreonine peptide with pT+3 specificity. So far there are two well characterised motifs: TXX[ILV] and TXX[DE]. While TXXC and TXXA have been observed, they are not currently modeled in ELM. The TXXC linear motif forms part of a larger induced fit interaction with the FHA domain (Li,2000; Yongkiettrakul,2004; Lee,2003). More variations among the FHA-binding motifs are expected to be found.
o 22 selected references:

o 7 GO-Terms:

o 6 Instances for LIG_FHA_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q8NQJ3 odhI
12 18 GTPEPQVETTSVFRADLLKE TP 7 Corynebacterium glutamicum ATCC 13032
P9WJA9 garA
19 25 TSDEVTVETTSVFRADFLSE TP 2 Mycobacterium tuberculosis H37Rv
P34217 PIN4
303 309 QLDFNDPDTLEIYSQLLLFK TP 5 Saccharomyces cerevisiae (Baker"s yeast)
P14737 RAD9
601 607 TIMSEVELTQELPEVEEQQD TP 2 Saccharomyces cerevisiae (Baker"s yeast)
866 872 YIAPEYAYTLKVDEKSDVYS TP 1 Arabidopsis thaliana (Thale cress)
O96017 CHEK2
66 72 LSSLETVSTQELYSIPEDQE TP 1 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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