The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
PCNA binding PIP box
Functional site description:
The PCNA binding PIP box motif is found in proteins involved in DNA replication, repair, methylation and cell cycle control.
ELM Description:
The classical PCNA binding PIP Box has a core amphipathic helix which docks by the hydrophobic face into a pocket on PCNA. The first helical turn provides an aliphatic residue, often Leucine. The second helical turn provides two hydrophobic positions, being most often Phenylalanine but almost always aromatic. Preceding the PIP box helix, an amide functional group is typically present either as the protein N-terminus, or as a Glutamine residue. Following the core PIP box helix, there are no required amino acid residues. However, there are usually additional interactions that contribute to the binding affinity, for example beta augmentation backbone interactions. Many PIP boxes have positively charged residues after the core helix and, for the PIP box degrons that also bind the Cdt2 ubiquitin ligase (DEG_CRL4_Cdt2_1 and DEG_CRL4_Cdt2_2), multiple positive charges are always present.
Pattern: ((^.{0,3})|(Q)).[^FHWY][ILM][^P][^FHILVWYP][HFM][FMY]..
Pattern Probability: 0.0000017
Present in taxons: cellular organisms Eukaryota
Interaction Domain:
PCNA_C (PF02747) Proliferating cell nuclear antigen, C-terminal domain (Stochiometry: 1 : 1)
PDB Structure: 2OD8
o See 18 Instances for LIG_PCNA_PIPBox_1
o Abstract
The PCNA binding site is a linear motif that mediates interaction with PCNA (Proliferating Cell Nuclear Antigen), the "sliding clamp" that associates proteins with the DNA replication fork. Among such proteins are enzymes involved in DNA replication, DNA repair and DNA methylation. Some proteins involved in cell cycle control also have PCNA binding sites. The site forms a short alpha helix which interacts with a patch on the outer surface of the clamp. The classical PCNA binding motif is termed the PIP Box. A variant PIP degron motif not only interacts with PCNA but also binds the CRL4-Cdt2 ubiquitin ligase for degradation after DNA damage or during S-phase. The PIP Box is remarkable in that it is one of the few linear motifs found in all kingdoms of life: Fen1 has a C-terminal PIP box-like motif in Eubacteria and Archaea as well as in Eukaryotes.
o 2 selected references:

o 7 GO-Terms:

o 18 Instances for LIG_PCNA_PIPBox_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P47110 POL32
338 347 SNKRLKKQGTLESFFKRKAK TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P07276 RAD2
995 1004 KKKGKQKRINEFFPREYISG TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P39748 FEN1
337 346 RQGSTQGRLDDFFKVTGSLS TP 2 Homo sapiens (Human)
Q03834 MSH6
27 36 QKKMKQSSLLSFFSKQVPSG TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P25336 MSH3
4 13 MAGQPTISRFFKKAVKSELT TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P26793 RAD27
340 349 LKSGIQGRLDGFFQVVPKTK TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P18858 LIG1
1 11 MQRSIMSFFHPKKEGKAKKP TP 1 Homo sapiens (Human)
P38630 RFC1
1 10 MVNISDFFGKNKKSVRSSTS TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P26358 DNMT1
164 173 RKSTRQTTITSHFAKGPAKR TP 1 Homo sapiens (Human)
P13051 UNG
4 13 MIGQKTLYSFFSPSPARKRH TP 1 Homo sapiens (Human)
P30261 cdc27
362 371 KNTAQSKPQQKSIMSFFGKK TP 1 Schizosaccharomyces pombe (Fission yeast)
P04819 CDC9
38 47 GKKPKQATLARFFTSMKNKP TP 4 Saccharomyces cerevisiae (Baker"s yeast)
P38766 RRM3
35 44 SHAYRQQTLSSFFMGCGKKS TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P12887 UNG1
21 30 ARKRKQTTIEDFFGTKKSTN TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q15054 POLD3
456 465 TAALGKANRQVSITGFFQRK TP 1 Homo sapiens (Human)
P38936 CDKN1A
144 153 GRKRRQTSMTDFYHSKRRLI TP 1 Homo sapiens (Human)
P28715 ERCC5
990 999 DAQQTQLRIDSFFRLAQQEK TP 1 Homo sapiens (Human)
P52701 MSH6
4 13 MSRQSTLYSFFPKSPALSDA TP 1 Homo sapiens (Human)
Please cite: The eukaryotic linear motif resource - 2018 update. (PMID:29136216)

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