 << LIG_FAT_LD_1 << |
Menu | >> LIG_FHA_2 >> |
| 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: | LIG_FHA_1 LIG_FHA_2 |
| Description: | LIG_FHA_1 motifs are short phosphothreonine modules binding FHA domains with large aliphatic aminoacids 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 (Smerdon et al.,2002) and DNA repair protein rad9 (Byeon et al.,2001). |
| Pattern: | ..(T)..[ILV]. (Probability: 0.0086622) |
| Present in taxons: |
 Eukaryota
|
PDB Structure:  1K2N 
|
|
| Interaction Domain: |
|
|
| The forkhead-associated FHA domain is a phosphopeptide-binding domain first identified in a group of forkhead transcription factors (Hofmann and Bucher, 1995). FHA are small domains (<100 aminoacids) which form a sandwich of two antiparallel beta sheets (Walker et al., 2000). They are present in a wide variety of proteins from both prokaryotes and eukaryotes (Walker et al., 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 (Doren et al., 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 (Li et al., 2003). So far there are two well characterised motifs TXX[ILV] and TXX[DE] - while TXXC and TXXA have been observed, they are not currently modelled in ELM. The TXXC linear motif forms part of a larger induced fit interaction with the FHA domain (Byeon et al.,2004). More variations among the FHA-binding motifs are expected to be found. |
22 selected references:
7 GO-Terms:
5 Instances for LIG_FHA_1
(click table headers for sorting)
| Sequence | Start | End | Subsequence | Instance Logic | PDB | Organism |
|---|---|---|---|---|---|---|
 CHK2_HUMAN |
66 | 72 | LSSLETVSTQELYSIPEDQE | true positive | --- |
Homo sapiens
(Human)
|
|
CLV1_ARATH |
866 | 872 | YIAPEYAYTLKVDEKSDVYS | true positive | --- |
Arabidopsis thaliana
(Thale cress)
|
|
RAD9_YEAST |
601 | 607 | TIMSEVELTQELPEVEEQQD | true positive | 1K2N |
Saccharomyces cerevisiae
(Baker"s yeast)
|
|
Y1827_MYCTU |
19 | 25 | TSDEVTVETTSVFRADFLSE | true positive | 2KFU |
Mycobacterium tuberculosis
|
|
PIN4_YEAST |
303 | 309 | QLDFNDPDTLEIYSQLLLFK | true positive | 2A0T |
Saccharomyces cerevisiae
(Baker"s yeast)
|
Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)
ELM data can be downloaded and distributed for non-commercial use according to the ELM Software License Agreement