The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
PP1-docking motif RVXF
Functional site description:
Protein phosphatase-1(PP1) is a major Ser/Thr protein phosphatase of the eukaryotic cell. PP1 naturally occurs as three different isoforms in vertebrates, encoded by the alpha, gamma1, and delta genes and in yeast the PP1 catalytic subunit is encoded by GLC7. PP1 is involved in regulating diverse cellular functions including glycogen metabolism, muscle contraction, the exit from mitosis and the splicing of RNA. The catalytic PP1 subunits recognize PP1-docking motifs in their regulatory subunits, which provide the substrate targeting specificity. The interaction is mainly through the hydrophobic patch of PP1 and the RVXF motif (DOC_PP1_RVXF_1) of the regulatory subunit. However, other PP1-docking motifs such as the SILK motif (DOC_PP1_SILK_1) and the MyPhoNE motif also play essential roles in regulating PP1 activity and substrate specificity (Hendrickx,2009).
ELMs with same tags:
ELM Description:
PP1c lacks intrinsic substrate specificity. The RVXF motif is found in regulatory subunits that either bridge PP1 with the substrates or inhibit PP1. A gap of one residue is also tolerated between R and V. The RVXF motif may also be flanked by positively charged amino acids at the N-terminus and negatively charged amino acids at the C-terminus. Even though PP1 exists in many isoforms, the consensus sequences of the PP1 binding motif is probably the same in all eukaryotes. This motif is probably always found in natively disordered polypeptide segments. However, something to watch out for is that the conserved hydrophobic residues will tend to generate false positives in globular domains.
Pattern: ..[RK].{0,1}[VIL][^P][FW].
Pattern Probability: 0.0008301
Present in taxon: Eukaryota
Interaction Domain:
Metallophos (PF00149) Calcineurin-like phosphoesterase (Stochiometry: 1 : 1)
PDB Structure: 1S70
o See 19 Instances for DOC_PP1_RVXF_1
o Abstract
Reversible protein serine/threonine phosphorylation is an important component of the intracellular signaling machinery. It regulates many of the process such as neurotransmission, muscle contraction, glycogen synthesis, T-cell activation, neuronal plasticity and cell proliferation (Aggen,2000). Protein serine/threonine phosphatases are divided into three structurally unrelated families. The PPM family comprises Mg2+-dependent enzymes, including protein phosphatase 2C (PP2C). The FCP family contains only one member, which is also Mg2+ dependent. All other protein serine/threonine phosphatases are classified in the PPP family, consisting of the subfamilies PP1, PP2A (including PP4 and PP6), PP2B, and PP5, all having a structurally related core and a similar catalytic mechanism (Ceulemans,2004).
In eukaryotes PP1 exists in a large number of isoforms. In humans PP1 is encoded by three highly related genes (PP1 alpha, PP1 beta/delta and PP1 gamma), and alternative splicing generates the gamma1 and gamma2 isoforms. While Saccharomyces cerevisiae is an exception, with only one PP1 gene (glc7), many eukaryotes have multiple PP1 genes - 8 in Arabidopsis thaliana, 4 in Drosophila melanogaster and a predicted 30 in Caenorhabditis elegans (Moorhead,2007). The function of all these isoforms are presently unclear.
The regulatory subunits recruit active PP1c to dephosphorylate phosphothreonine or phosphoserine residues in the target substrates. Three grooves (hydrophobic, C-terminal, and acidic) have been defined on the surface of PP1 (Maynes,2001). The hydrophobic groove of PP1c interacts with the RVXF motif (DOC_PP1_RVXF_1) in the regulatory proteins. The RVXF peptide backbone binds by beta-augmentation within the hydrophobic patch. So far more than 90 regulatory protein of PP1 with this characterised motif are documented (Moorhead,2007). These mostly mediate substrate target selection but some are inhibitors of PP1 for example phospho-DARPP-32. Generally, RVXF motifs cooperate with distinct PP1-docking motifs to bind PP1. Additional characterized PP1-docking motifs are the SILK motif (DOC_PP1_SILK_1) and the MyPhoNE (myosin phosphatase N-terminal element) motif.
o 14 selected references:

o 14 GO-Terms:

o 19 Instances for DOC_PP1_RVXF_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P51955 NEK2
381 387 LPSSVIKKKVHFSGESKENI TP 4 Homo sapiens (Human)
Q92667 AKAP1
151 158 LECPLSSPKGVLFSSKSAEV TP 5 Homo sapiens (Human)
P08353 RL1
190 196 PATPATPARVRFSPHVRVRH TP 3 Herpes simplex virus (type 1 / strain F)
P06400 RB1
871 878 GSNPPKPLKKLRFDIEGSDE TP 4 Homo sapiens (Human)
O35867 Ppp1r9a
455 461 EEEIPANRKIKFSCAPIKVF TP 8 Rattus norvegicus (Norway rat)
O14974 PPP1R12A
33 39 PVVKRQKTKVKFDDGAVFLA TP 1 Homo sapiens (Human)
P38398 BRCA1
896 902 GSLKKQSPKVTFECEQKEEN TP 4 Homo sapiens (Human)
Q16821 PPP1R3A
61 67 DTPSSGTRRVSFADSFGFNL TP 2 Homo sapiens (Human)
O35274 Ppp1r9b
573 579 SVLRNTKGRVRFMIGRERPG TN 1 Rattus norvegicus (Norway rat)
Q90623 PPP1R12A
33 39 PVVKRKKTKVKFDDGAVFLA TP 1 Gallus gallus (Chicken)
Q00816 REG1
462 469 KSNKPTKNRHIHFNDRVEQC TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P28006 GAC1
67 74 EIFCTSPEKNVRFAIELTTV TP 3 Saccharomyces cerevisiae (Baker"s yeast)
P34758 SCD5
271 277 KNLNFKSKKVRFSEHITFQD TP 3 Saccharomyces cerevisiae (Baker"s yeast)
P34758 SCD5
238 244 SSAKTGDQKVDFDSFASLLL TP 3 Saccharomyces cerevisiae (Baker"s yeast)
5 12 MDPKDRKKIQFSVPAPPSQL TP 1 Homo sapiens (Human)
O88809 Dcx
52 58 LSNEKKAKKVRFYRNGDRYF TP 1 Mus musculus (House mouse)
Q96QC0 PPP1R10
395 402 LTRKGRKRKSVTWPEEGKLR TP 1 Homo sapiens (Human)
O35274 Ppp1r9b
446 452 EEDPAPSRKIHFSTAPIQVF TP 3 Rattus norvegicus (Norway rat)
Q12972 PPP1R8
198 204 PKRKRKNSRVTFSEDDEIIN TP 1 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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