The Eukaryote Linear Motif resource for Functional Sites in Proteins
Functional site class:
BRCT phosphopeptide ligands
Functional site description:
BRCT domains are protein modules mainly found in Eukaryota. BRCT domains are present in proteins that are associated with DNA damage response. They recognize and bind specific phosphorylated serine (pS) sequences. This phospho-protein mediated interaction of the BRCT domain has a central role in cell-cycle check point and DNA repair functions.
ELMs with this model: LIG_BRCT_BRCA1_1  LIG_BRCT_BRCA1_2  LIG_BRCT_MDC1_1 
Description:
The LIG_BRCT_MDC1_1 motif found in metazoa. The tandem BRCT repeats of MDC1 directly bind to the phosphorylated tail of H2AX (S..Y$), in a manner that is specific to the Carboxy-terminal Tyr residue. By homology, the equivalent motif may be S..F$ in plants or S..L$ in fungi but direct experimental evidence is lacking.
Pattern: .(S)..Y$
Pattern Probability: 0.0000026
Present in taxon: Metazoa
Interaction Domain:
BRCT (PF00533) BRCA1 C Terminus (BRCT) domain (Stochiometry: 1 : 1)
PDB Structure: 2AZM
<a style="white-space:nowrap;" href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2AZM" target="_blank"><img src="/media/pdb.ico.png"/>2AZM</a>
o See 1 Instance for LIG_BRCT_MDC1_1
o Abstract
BRCT domains were first identified in and named after the breast cancer susceptibility protein BRCA1 (Zhang,1999). They have alpha/beta structures that occur singly or as multiple repeats. BRCT domains are 80-100 amino acid in length and function as phosphopeptide ligands (Clapperton,2004). They are found in nuclear proteins that are typically associated with cell cycle checkpoint functions responsive to DNA damage (Glover,2004). An unusual feature of paired BRCT motifs is that the phosphopeptides bind across the domain-domain interface (Clapperton,2004). Available data when this entry was prepared suggest that BRCTs may bind exclusively to phosphoserine peptides. By contrast FHA domains, which are often found in a similar functional context, recognise phosphothreonine peptides (LIG_FHA_1). Many of the BRCT ligands are likely to be at pSQ motifs phosphorylated by the checkpoint kinases, ATM, ATR, DNA-PK (Glover,2004). BRCA1-binding motifs are S..F.K (high affinity) or S..F (lower affinity) (Clapperton,2004). Metazoan MDC1 binds histone H2AX C-terminal S..Y$ motifs (Lee,2005), which may be S..F$ in plants and S..L$ in fungi, but experimental evidence has been lacking. Also, a poorly characterised motif binding the TopBP1 BRCT may match the pattern S.II but more data is needed (Liu,2003). Since consensus motifs have so far been defined for just a few BRCT domains, the range of different binding motif patterns could be quite large.

o 3 selected references:

o 4 GO-Terms:

o 1 Instance for LIG_BRCT_MDC1_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
H2AX_HUMAN H2AFX 139 143 TVGPKAPSGGKKATQASQEY TP 4 Homo sapiens (Human)
1 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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