LIG_PP1
ELM server details
ELM
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Functional site class:
 PP1 docking motif
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. However they recognize a common PP1 binding motif in their regulatory subunits which provide the substrate targeting specificity. The interaction is mainly through the hydrophobic patch of PP1 and the RVXF motif of the regulatory subunit. PP1 is involved in regulating diverse cellular functions including glycogen metabolism, muscle contraction, the exit from mitosis and the splicing of RNA.
ELM(s): LIG_PP1
LIG_PP1 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}[VI][^P][FW].
Present in taxon(s): Eukaryota  
Not represented in taxon(s):

o See instances for LIG_PP1


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 et.al., 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 H and Bollen M, 2003).
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 et.al., 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 (James et.al., 2001). The hydrophobic groove of PP1c interacts with the RVXF motif 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 et.al., 2007). These mostly mediate substrate target selection but some are inhibitors of PP1 for example phospho-DARPP-32.

o Selected references

Aggen JB, Nairn AC, Chamberlin R
Regulation of protein phosphatase-1.
Chem Biol 2000 Jan;7(1) : R13-23.
PMID: 10662690

Armstrong CG, Doherty MJ, Cohen PT
Identification of the separate domains in the hepatic glycogen-targeting subunit of protein phosphatase 1 that interact with phosphorylase a, glycogen and protein phosphatase 1.
Biochem J 1998 Dec 15;336() : 699-704.
PMID: 9841883

Beullens M, Van Eynde A, Vulsteke V, Connor J, Shenolikar S, Stalmans W, Bollen M
Molecular determinants of nuclear protein phosphatase-1 regulation by NIPP-1.
J Biol Chem 1999 May 14;274(20) : 14053-61.
PMID: 10318819

Cohen PT
Protein phosphatase 1--targeted in many directions.
J Cell Sci 2002 Jan 15;115() : 241-56.
PMID: 11839776

Dombek KM, Voronkova V, Raney A, Young ET
Functional analysis of the yeast Glc7-binding protein Reg1 identifies a protein phosphatase type 1-binding motif as essential for repression of ADH2 expression.
Mol Cell Biol 1999 Sep;19(9) : 6029-40.
PMID: 10454550

Egloff MP, Johnson DF, Moorhead G, Cohen PT, Cohen P, Barford D
Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1.
EMBO J 1997 Apr 15;16(8) : 1876-87.
PMID: 9155014

Hsu LC
Identification and functional characterization of a PP1-binding site in BRCA1.
Biochem Biophys Res Commun 2007 Aug 24;360(2) : 507-12.
PMID: 17603999

Kees U, Kaltmann B, Marcucci F, Hultner L, Staber F, Krammer PH
Frequency and activity of immune interferon (IFN-gamma)- and colony-stimulating factor-producing human peripheral blood T lymphocytes.
Eur J Immunol 1984 Apr;14(4) : 368-73.
PMID: 6426971

Liu J, Wu J, Oliver C, Shenolikar S, Brautigan DL
Mutations of the serine phosphorylated in the protein phosphatase-1-binding motif in the skeletal muscle glycogen-targeting subunit.
Biochem J 2000 Feb 15;346() : 77-82.
PMID: 10657242

Maynes JT, Bateman KS, Cherney MM, Das AK, Luu HA, Holmes CF, James MN
Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1.
J Biol Chem 2001 Nov 23;276(47) : 44078-82.
PMID: 11535607

Moorhead GB, Trinkle-Mulcahy L, Ulke-Lemee A
Emerging roles of nuclear protein phosphatases.
Nat Rev Mol Cell Biol 2007 Mar;8(3) : 234-44.
PMID: 17318227

Neduva V, Linding R, Su-Angrand I, Stark A, de Masi F, Gibson TJ, Lewis J, Serrano L, Russell RB
Systematic discovery of new recognition peptides mediating protein interaction networks.
PLoS Biol 2005 Dec;3(12) : e405.
PMID: 16279839

Terrak M, Kerff F, Langsetmo K, Tao T, Dominguez R
Structural basis of protein phosphatase 1 regulation.
Nature 2004 Jun 17;429(6993) : 780-4.
PMID: 15164081

Wakula P, Beullens M, Ceulemans H, Stalmans W, Bollen M
Degeneracy and function of the ubiquitous RVXF motif that mediates binding to protein phosphatase-1.
J Biol Chem 2003 May 23;278(21) : 18817-23.
PMID: 12657641

o This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
  Cell growth and/or maintenance
  cell cycle
  glycogen metabolism
  protein amino acid dephosphorylation
  muscle contraction
  signal transduction
Cellular Component
  nucleus
  protein phosphatase type 1 complex
  cytosol
Molecular Function
  protein binding
  protein phosphatase 1 binding
  type 1 serine/threonine specific protein phosphatase inhibitor
  Binding
  protein phosphatase inhibitor

 

o Instances for LIG_PP1

SequencePositionSubsequence
(Click for evidence information)		PDBGene NameProtein DescriptionOrganism
BRCA1_HUMAN 896-902 SLKKQSPKVTFECEQKEE - Name=BRCA1; Synonyms=RNF53; Breast cancer type 1 susceptibility protein (RING finger protein 53). Homo sapiens (Human).
MYPT1_HUMAN 33-39 VVKRQKTKVKFDDGAVFL 1S70
1S70
 Name=PPP1R12A; Synonyms=MBS, MYPT1; Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase- targeting subunit 1) (Myosin phosphatase target subunit 1) (Protein phosphatase myosin-binding subunit). Homo sapiens (Human).
PP1R8_HUMAN 198-204 KRKRKNSRVTFSEDDEII - Name=PPP1R8; Synonyms=ARD1, NIPP1; Nuclear inhibitor of protein phosphatase 1 (NIPP-1) (Protein phosphatase 1 regulatory inhibitor subunit 8) [Includes: Activator of RNA decay (EC 3.1.4.-) (ARD-1)]. Homo sapiens (Human).
NEB2_RAT 446-452 EDPAPSRKIHFSTAPIQV - Name=Ppp1r9b; Neurabin-2 (Neurabin-II) (Spinophilin) (Protein phosphatase 1 regulatory subunit 9B) (Neural tissue-specific F-actin-binding protein II) (p130) (PP1bp134). Rattus norvegicus (Rat).
NEB1_RAT 455-461 EEIPANRKIKFSCAPIKV - Name=Ppp1r9a; Neurabin-1 (Neurabin-I) (Neural tissue-specific F-actin-binding protein I) (Protein phosphatase 1 regulatory subunit 9A) (p180) (PP1bp175). Rattus norvegicus (Rat).
PP1RA_HUMAN 395-402 TRKGRKRKSVTWPEEGKLR - Name=PPP1R10; Synonyms=CAT53, FB19, PNUTS; Serine/threonine-protein phosphatase 1 regulatory subunit 10 (Phosphatase 1 nuclear targeting subunit) (MHC class I region proline- rich protein CAT53) (FB19 protein) (PP1-binding protein of 114 kDa) (p99). Homo sapiens (Human).
DCX_MOUSE 52-58 SNEKKAKKVRFYRNGDRY - Name=Dcx; Synonyms=Dcn; Neuronal migration protein doublecortin (Lissencephalin-X) (Lis-X) (Doublin). Mus musculus (Mouse).
PPR1B_HUMAN 5-12 MDPKDRKKIQFSVPAPPS - Name=PPP1R1B; Synonyms=DARPP32; Protein phosphatase 1 regulatory subunit 1B (Dopamine- and cAMP- regulated neuronal phosphoprotein) (DARPP-32). Homo sapiens (Human).
SCD5_YEAST 238-244 SAKTGDQKVDFDSFASLL - Name=SCD5; Synonyms=FTB1; OrderedLocusNames=YOR329C; Protein SCD5 (Protein FTB1). Saccharomyces cerevisiae (Baker's yeast).
SCD5_YEAST 271-277 NLNFKSKKVRFSEHITFQ - Name=SCD5; Synonyms=FTB1; OrderedLocusNames=YOR329C; Protein SCD5 (Protein FTB1). Saccharomyces cerevisiae (Baker's yeast).
GAC1_YEAST 67-74 IFCTSPEKNVRFAIELTTV - Name=GAC1; OrderedLocusNames=YOR178C; Serine/threonine-protein phosphatase 1 regulatory subunit GAC1. Saccharomyces cerevisiae (Baker's yeast).
HEX2_YEAST 462-469 SNKPTKNRHIHFNDRVEQC - Name=HEX2; Synonyms=REG1, SPP43, SRN1; OrderedLocusNames=YDR028C; ORFNames=YD9813.06C; Protein HEX2 (Protein SRN1) (Protein REG1). Saccharomyces cerevisiae (Baker's yeast).
A4D0T6_HUMAN 61-67 TPSSGTRRVSFADSFGFN - Name=PPP1R3A; ORFNames=tcag7.100; Protein phosphatase 1, regulatory (Inhibitor) subunit 3A (Glycogen and sarcoplasmic reticulum binding subunit, skeletal muscle). Homo sapiens (Human).