The Eukaryote 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_2 motifs are short phosphothreonine peptide modules contains acidic amino acids at the pT+3 position. The motif has the consensus sequence of T..[ED]. FHA domains with this preference are found in checkpoint/repair proteins MRC1 and Rad9 of fungi and metazoan Xrcc1 (Luo,2004) and Xrcc4 (Koch,2004).
Pattern: ..(T)..[DE].
Pattern Probability: 0.0082864
Present in taxon: Eukaryota
Interaction Domain:
FHA (PF00498) FHA domain (Stochiometry: 1 : 1)
PDB Structure: 1K3Q
<a href="" title="" target="_blank"><img src="/media/pdb.ico.png"/>1K3Q</a>
o See 6 Instances for LIG_FHA_2
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 4 selected references:

o 7 GO-Terms:

o 6 Instances for LIG_FHA_2
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P18887 XRCC1
521 527 YAGSTDENTDSEEHQEPPDL TP 2 Homo sapiens (Human)
P14737 RAD9
190 196 EENASLEVTEADATFVQMAE TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P14737 RAD9
153 159 LRKKMTFQTPTDPLEQKTFK TP 2 Saccharomyces cerevisiae (Baker"s yeast)
Q924T3 Xrcc4
229 235 EHGLYDGSTDEESGAPVQAA TP 1 Mus musculus (House mouse)
Q9P7T4 mrc1
643 649 SQVDSLVPTQLDSTIPTQID TP 2 Schizosaccharomyces pombe (Fission yeast)
Q13426 XRCC4
231 237 RDPVYDESTDEESENQTDLS TP 4 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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