PDBsum entry 1hsq

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Phosphoric diester hydrolase PDB id
Protein chain
71 a.a. *
* Residue conservation analysis
PDB id:
Name: Phosphoric diester hydrolase
Title: Solution structure of the sh3 domain of phospholipase cgamma
Structure: PhospholipasE C-gamma (sh3 domain). Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: grb2
NMR struc: 1 models
Authors: D.Kohda,H.Hatanaka,M.Odaka,F.Inagaki
Key ref: D.Kohda et al. (1993). Solution structure of the SH3 domain of phospholipase C-gamma. Cell, 72, 953-960. PubMed id: 7681365
13-Jun-94     Release date:   31-Aug-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P19174  (PLCG1_HUMAN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
1290 a.a.
71 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   1 term 


Cell 72:953-960 (1993)
PubMed id: 7681365  
Solution structure of the SH3 domain of phospholipase C-gamma.
D.Kohda, H.Hatanaka, M.Odaka, V.Mandiyan, A.Ullrich, J.Schlessinger, F.Inagaki.
SH3 (Src homology 3) domains are found in many signaling proteins and appear to function as binding modules for cytoplasmic target proteins. The solution structure of the SH3 domain of human phospholipase C-gamma (PLC-gamma) was determined by two-dimensional 1H NMR analysis. This SH3 domain is composed of eight antiparallel beta strands consisting of two successive "Greek key" motifs, which form a barrel-like structure. The conserved aliphatic and aromatic residues form a hydrophobic pocket on the molecular surface, and the conserved carboxylic residues are localized to the periphery. The hydrophobic pocket may serve as a binding site for target proteins. Analysis of the slowly exchanging amide protons by NMR measurements indicates that despite containing a high content of beta structure, the SH3 domain of PLC-gamma is flexible.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20930476 F.Inagaki (2010).
[On the occasion of retirement from Graduate School of Pharmaceutical Sciences, Hokkaido University].
  Yakugaku Zasshi, 130, 1251-1262.  
20084418 K.Prymula, K.SaƂapa, and I.Roterman (2010).
"Fuzzy oil drop" model applied to individual small proteins built of 70 amino acids.
  J Mol Model, 16, 1269-1282.  
19531496 K.L.Everett, T.D.Bunney, Y.Yoon, F.Rodrigues-Lima, R.Harris, P.C.Driscoll, K.Abe, H.Fuchs, Angelis, P.Yu, W.Cho, and M.Katan (2009).
Characterization of phospholipase C gamma enzymes with gain-of-function mutations.
  J Biol Chem, 284, 23083-23093.  
16061254 L.Deng, C.A.Velikovsky, C.P.Swaminathan, S.Cho, and R.A.Mariuzza (2005).
Structural basis for recognition of the T cell adaptor protein SLP-76 by the SH3 domain of phospholipase Cgamma1.
  J Mol Biol, 352, 1.
PDB codes: 1ywo 1ywp
11682324 M.Vidal, V.Gigoux, and C.Garbay (2001).
SH2 and SH3 domains as targets for anti-proliferative agents.
  Crit Rev Oncol Hematol, 40, 175-186.  
  11206067 A.Rath, and A.R.Davidson (2000).
The design of a hyperstable mutant of the Abp1p SH3 domain by sequence alignment analysis.
  Protein Sci, 9, 2457-2469.  
  11206052 Y.Kuroda, K.Tani, Y.Matsuo, and S.Yokoyama (2000).
Automated search of natively folded protein fragments for high-throughput structure determination in structural genomics.
  Protein Sci, 9, 2313-2321.  
10535955 P.Koehl, and M.Levitt (1999).
Structure-based conformational preferences of amino acids.
  Proc Natl Acad Sci U S A, 96, 12524-12529.  
10570253 R.L.Williams (1999).
Mammalian phosphoinositide-specific phospholipase C.
  Biochim Biophys Acta, 1441, 255-267.  
10574999 W.L.Lee, E.M.Ostap, H.G.Zot, and T.D.Pollard (1999).
Organization and ligand binding properties of the tail of Acanthamoeba myosin-IA. Identification of an actin-binding site in the basic (tail homology-1) domain.
  J Biol Chem, 274, 35159-35171.  
9819209 K.L.Maxwell, and A.R.Davidson (1998).
Mutagenesis of a buried polar interaction in an SH3 domain: sequence conservation provides the best prediction of stability effects.
  Biochemistry, 37, 16172-16182.  
9838022 M.Katan (1998).
Families of phosphoinositide-specific phospholipase C: structure and function.
  Biochim Biophys Acta, 1436, 5.  
9629920 R.K.Rasmussen, H.Ji, J.S.Eddes, R.L.Moritz, G.E.Reid, R.J.Simpson, and D.S.Dorow (1998).
Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins.
  Electrophoresis, 19, 809-817.  
9593201 S.Knapp, P.T.Mattson, P.Christova, K.D.Berndt, A.Karshikoff, M.Vihinen, C.I.Smith, and R.Ladenstein (1998).
Thermal unfolding of small proteins with SH3 domain folding pattern.
  Proteins, 31, 309-319.  
9038203 A.M.Castellino, G.J.Parker, I.V.Boronenkov, R.A.Anderson, and M.V.Chao (1997).
A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase.
  J Biol Chem, 272, 5861-5870.  
9566119 D.C.Dalgarno, M.C.Botfield, and R.J.Rickles (1997).
SH3 domains and drug design: ligands, structure, and biological function.
  Biopolymers, 43, 383-400.  
9408950 H.V.Patel, S.R.Tzeng, C.Y.Liao, S.H.Chen, and J.W.Cheng (1997).
SH3 domain of Bruton's tyrosine kinase can bind to proline-rich peptides of TH domain of the kinase and p120cbl.
  Proteins, 29, 545-552.  
  9144769 J.E.Gready, S.Ranganathan, P.R.Schofield, Y.Matsuo, and K.Nishikawa (1997).
Predicted structure of the extracellular region of ligand-gated ion-channel receptors shows SH2-like and SH3-like domains forming the ligand-binding site.
  Protein Sci, 6, 983-998.  
9034330 K.Q.Hu, and J.Settleman (1997).
Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: a conformational mechanism for SH3 domain regulation.
  EMBO J, 16, 473-483.  
9303002 K.V.Kishan, G.Scita, W.T.Wong, P.P.Di Fiore, and M.E.Newcomer (1997).
The SH3 domain of Eps8 exists as a novel intertwined dimer.
  Nat Struct Biol, 4, 739-743.
PDB code: 1aoj
8805554 C.J.Morton, D.J.Pugh, E.L.Brown, J.D.Kahmann, D.A.Renzoni, and I.D.Campbell (1996).
Solution structure and peptide binding of the SH3 domain from human Fyn.
  Structure, 4, 705-714.
PDB codes: 1nyf 1nyg
  8605874 D.C.Chan, M.T.Bedford, and P.Leder (1996).
Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains.
  EMBO J, 15, 1045-1054.  
8630736 H.Park, M.I.Wahl, D.E.Afar, C.W.Turck, D.J.Rawlings, C.Tam, A.M.Scharenberg, J.P.Kinet, and O.N.Witte (1996).
Regulation of Btk function by a major autophosphorylation site within the SH3 domain.
  Immunity, 4, 515-525.  
8718852 M.T.Pisabarro, and L.Serrano (1996).
Rational design of specific high-affinity peptide ligands for the Abl-SH3 domain.
  Biochemistry, 35, 10634-10640.  
8824280 P.M.Finan, C.J.Soames, L.Wilson, D.L.Nelson, D.M.Stewart, O.Truong, J.J.Hsuan, and S.Kellie (1996).
Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.
  J Biol Chem, 271, 26291-26295.  
8994965 R.L.Williams, and M.Katan (1996).
Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead.
  Structure, 4, 1387-1394.  
8536694 D.S.Dorow, L.Devereux, G.F.Tu, G.Price, J.K.Nicholl, G.R.Sutherland, and R.J.Simpson (1995).
Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2.
  Eur J Biochem, 234, 492-500.  
  7708014 E.M.Phizicky, and S.Fields (1995).
Protein-protein interactions: methods for detection and analysis.
  Microbiol Rev, 59, 94.  
9383403 J.A.Simon, and S.L.Schreiber (1995).
Grb2 SH3 binding to peptides from Sos: evaluation of a general model for SH3-ligand interactions.
  Chem Biol, 2, 53-60.  
7536925 K.Alexandropoulos, G.Cheng, and D.Baltimore (1995).
Proline-rich sequences that bind to Src homology 3 domains with individual specificities.
  Proc Natl Acad Sci U S A, 92, 3110-3114.  
7782338 M.Sudol, P.Bork, A.Einbond, K.Kastury, T.Druck, M.Negrini, K.Huebner, and D.Lehman (1995).
Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain.
  J Biol Chem, 270, 14733-14741.  
7612269 S.B.Lee, and S.G.Rhee (1995).
Significance of PIP2 hydrolysis and regulation of phospholipase C isozymes.
  Curr Opin Cell Biol, 7, 183-189.  
  7534229 T.Erpel, G.Superti-Furga, and S.A.Courtneidge (1995).
Mutational analysis of the Src SH3 domain: the same residues of the ligand binding surface are important for intra- and intermolecular interactions.
  EMBO J, 14, 963-975.  
7664083 A.Musacchio, M.Saraste, and M.Wilmanns (1994).
High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides.
  Nat Struct Biol, 1, 546-551.
PDB codes: 1abo 1abq 1fyn
8066087 B.Rost, and C.Sander (1994).
Combining evolutionary information and neural networks to predict protein secondary structure.
  Proteins, 19, 55-72.  
7953536 C.J.Morton, and I.D.Campbell (1994).
SH3 domains. Molecular 'Velcro'.
  Curr Biol, 4, 615-617.  
7664069 D.Cowburn (1994).
Helical encounter.
  Nat Struct Biol, 1, 489-491.  
  7521298 D.Cussac, M.Frech, and P.Chardin (1994).
Binding of the Grb2 SH2 domain to phosphotyrosine motifs does not change the affinity of its SH3 domains for Sos proline-rich motifs.
  EMBO J, 13, 4011-4021.  
7881903 D.Kohda, H.Terasawa, S.Ichikawa, K.Ogura, H.Hatanaka, V.Mandiyan, A.Ullrich, J.Schlessinger, and F.Inagaki (1994).
Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2.
  Structure, 2, 1029-1040.
PDB codes: 1gfc 1gfd
  7520528 G.Panchamoorthy, T.Fukazawa, L.Stolz, G.Payne, K.Reedquist, S.Shoelson, Z.Songyang, L.Cantley, C.Walsh, and H.Band (1994).
Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn.
  Mol Cell Biol, 14, 6372-6385.  
7773778 H.Terasawa, D.Kohda, H.Hatanaka, S.Tsuchiya, K.Ogura, K.Nagata, S.Ishii, V.Mandiyan, A.Ullrich, and J.Schlessinger (1994).
Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos.
  Nat Struct Biol, 1, 891-897.  
7545075 H.Yu, and S.L.Schreiber (1994).
Signalling an interest.
  Nat Struct Biol, 1, 417-420.  
  8062828 K.Nagata, D.Kohda, H.Hatanaka, S.Ichikawa, S.Matsuda, T.Yamamoto, A.Suzuki, and F.Inagaki (1994).
Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.
  EMBO J, 13, 3517-3523.
PDB codes: 1hre 1hrf
7892170 M.T.Pisabarro, A.R.Ortiz, L.Serrano, and R.C.Wade (1994).
Homology modeling of the Abl-SH3 domain.
  Proteins, 20, 203-215.
PDB code: 1abl
7773779 N.Goudreau, F.Cornille, M.Duchesne, F.Parker, B.Tocqué, C.Garbay, and B.P.Roques (1994).
NMR structure of the N-terminal SH3 domain of GRB2 and its complex with a proline-rich peptide from Sos.
  Nat Struct Biol, 1, 898-907.  
7519238 Q.Zhu, M.Zhang, D.J.Rawlings, M.Vihinen, T.Hagemann, D.C.Saffran, S.P.Kwan, L.Nilsson, C.I.Smith, O.N.Witte, S.H.Chen, and H.D.Ochs (1994).
Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).
  J Exp Med, 180, 461-470.  
7945274 R.H.Sohn, and P.J.Goldschmidt-Clermont (1994).
Profilin: at the crossroads of signal transduction and the actin cytoskeleton.
  Bioessays, 16, 465-472.  
  7969134 R.R.Mattingly, A.Sorisky, M.R.Brann, and I.G.Macara (1994).
Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain.
  Mol Cell Biol, 14, 7943-7952.  
7656049 W.A.Lim, and F.M.Richards (1994).
Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition.
  Nat Struct Biol, 1, 221-225.  
  7987221 W.A.Lim, R.O.Fox, and F.M.Richards (1994).
Stability and peptide binding affinity of an SH3 domain from the Caenorhabditis elegans signaling protein Sem-5.
  Protein Sci, 3, 1261-1266.  
  8137811 Y.S.Yang, C.Garbay, M.Duchesne, F.Cornille, N.Jullian, N.Fromage, B.Tocque, and B.P.Roques (1994).
Solution structure of GAP SH3 domain by 1H NMR and spatial arrangement of essential Ras signaling-involved sequence.
  EMBO J, 13, 1270-1279.  
8402898 I.Gout, R.Dhand, I.D.Hiles, M.J.Fry, G.Panayotou, P.Das, O.Truong, N.F.Totty, J.Hsuan, and G.W.Booker (1993).
The GTPase dynamin binds to and is activated by a subset of SH3 domains.
  Cell, 75, 25-36.  
  8268793 M.J.Fry, G.Panayotou, G.W.Booker, and M.D.Waterfield (1993).
New insights into protein-tyrosine kinase receptor signaling complexes.
  Protein Sci, 2, 1785-1797.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.