The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
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 same func. site: LIG_BRCT_BRCA1_1  LIG_BRCT_BRCA1_2  LIG_BRCT_MDC1_1 
ELM Description:
The LIG_BRCT_BRCA1_1 motif binds with low affinity to the BRCT domain of BRCA1. The motif has the consensus sequence S..F and these residues are specially recognized by the binding pocket in the BRCT domains. The high affinity motif has an additional bound lysine residue (S..F.K).
Pattern: .(S)..F
Pattern Probability: 0.0019115
Present in taxon: Eukaryota
Interaction Domain:
BRCT (PF00533) BRCA1 C Terminus (BRCT) domain (Stochiometry: 1 : 1)
PDB Structure: 3COJ
o See 5 Instances for LIG_BRCT_BRCA1_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). Metazoa 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 8 selected references:

o 5 GO-Terms:

o 5 Instances for LIG_BRCT_BRCA1_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q13085 ACACA
ACACA_HUMAN
1262 1266 CFSDSPPQSPTFPEAGHTSL TP 4 Homo sapiens (Human)
1 
Q6UWZ7 FAM175A
F175A_HUMAN
405 409 TDEEIEKMKGFGEYSRSPTF TP 3 Homo sapiens (Human)
1 
Q8WXE1 ATRIP
ATRIP_HUMAN
238 242 VVIKPEACSPQFGKTSFPTK TP 3 Homo sapiens (Human)
1 
Q99708 RBBP8
COM1_HUMAN
326 330 EELPTRVSSPVFGATSSIKS TP 2 Homo sapiens (Human)
1 
Q9BX63 BRIP1
FANCJ_HUMAN
989 993 KIVISRSTSPTFNKQTKRVS TP 4 Homo sapiens (Human)
1 
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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