The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
RPA32C ligand-binding site
Functional site description:
The RPA interacting motif is conserved in eukaryotes DNA repair and replication proteins UNG2, XPA, RAD14, TIPIN and SMARCAL1. It is involved in DNA replication and other DNA processing pathways by binding to RPA. This protein-mediated RPA conformation is also known as ‘hand-off’ model. The interaction between RPA interacting motif and RPA32C are weak but specific.
ELMs with same func. site: LIG_RPA_C_Fungi  LIG_RPA_C_Insects  LIG_RPA_C_Plants  LIG_RPA_C_Vert 
ELM Description:
The RPA interacting motif is embedded in DNA replication and repair proteins UNG2 (P13051), XPA (P23025), TIPIN (Q9BVW5), SMARCAL1 (Q9NZC9) and RAD14 (P28519) and essential for RPA (PF08784) binding. This motif generally cooperates with the RPA32 C-terminal residues, adopting a compact globular α/β domain structure consisting of a right-handed three-helix bundle and a short three-stranded antiparallel β sheet. The binding involves hydrophobic and electrostatic interactions, which are mainly mediated by conserved hydrophobic and positively charged residues. The first amino acid of the motif is LYS or ARG, in rare cases SER. These amino acid residues interact with the negatively charged side chain of RAP32. The highly conserved hydrophobic amino acid isoleucine in the second position forms hydrophobic contacts with the side chains of S257 or T258. The charged amino acids in position five and six play an important role in the binding interaction of the motif by binding Y256 of RPA32. The aromatic ring of Y256 occupies a central position at the surface of RPA32 and participates in van der Waals contacts with the protons of positively charged amino acids. Alanine in the ninth position contributes in hydrophobic interactions with amino acid residues Y256 and T267 of the RPA32 molecule. The mostly positive charged amino acids in the twelfth and thirteenth position form hydrogen bonds with the backbone carbonyl of S250 and contribute in water-mediated hydrogen bonds with the RPA32C backbone hydroxyl group of T267. The last amino acid in the motif is LYS or ARG. These positively charged amino acids electrostatically interact with E252 of the RPA32 molecule (Mer,2000, 1DPU). The structure of SMARCAL1 binding to RPA32C shows a longer motif than described, but these amino acids are not highly conserved in other binding proteins and therefore are not required for binding to RPA32C, they just provide a better binding affinity (Xie,2014, 4MQV).
Pattern: [KRS]I[^P][^P][NK][KR][^P][^P]A[^P][^P][RKL][RKL][^P][^P][RK]
Pattern Probability: 1.210e-08
Present in taxon: Vertebrata
Interaction Domain:
RPA_C (PF08784) Replication protein A C terminal (Stochiometry: 1 : 1)
o See 4 Instances for LIG_RPA_C_Vert
o Abstract
Replication protein A (RPA) is a conserved eukaryotic single stranded DNA (ssDNA) binding protein and essential for DNA replication, recombination and repair. RPA consists of three subunits RPA70, RPA32 and RPA14, named after their molecular weight 70, 32 and 14 kDa, that form a stable complex (Fanning,2006). All three subunits consist primarily of OB fold domains that form the trimrization core and are responsible for ssDNA binding. Furthermore RPA70 N-terminal domain and RPA32 C-terminal domain can recruit a variety of DNA processing proteins in response to genomic stress and DNA damage (Xie,2014). The C terminus of subunit RPA32 contains a specific surface that interacts with a variety of DNA damage response proteins and therefore this region is required for base excision repair, nucleotide excision repair and S-phase checkpoint activation. RPA32C mediating the assembly of DNA repair complexes via a hand-off mechanism. In early steps of nucleotide excision repair and the repair of double-strand breaks by homologous recombination, RPA binds to the ssDNA opposite or adjacent to the site of DNA damage and interacts with one of the damage-recognition proteins (Mer,2000).
o 5 selected references:

o 12 GO-Terms:

o 4 Instances for LIG_RPA_C_Vert
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
202 217 QQRIERNKQLALERRQAKLL TP 6 Homo sapiens (Human)
P23025 XPA
27 42 RASIERKRQRALMLRQARLA TP 4 Homo sapiens (Human)
P13051 UNG
73 88 LDRIQRNKAAALLRLAARNV TP 3 Homo sapiens (Human)
12 27 RKKIEENRQKALARRAEKLL TP 8 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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