PDBsum entry 1pkt

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Phosphotransferase PDB id
Protein chain
76 a.a. *
* Residue conservation analysis
PDB id:
Name: Phosphotransferase
Title: Structure of the pi3k sh3 domain and analysis of the sh3 family
Structure: Phosphatidylinositol 3-kinase p85-alpha subunit sh3 domain. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
NMR struc: 30 models
Authors: S.Koyama,H.Yu,D.C.Dalgarno,T.B.Shin,L.D.Zydowsky, S.L.Schreiber
Key ref: S.Koyama et al. (1993). Structure of the PI3K SH3 domain and analysis of the SH3 family. Cell, 72, 945-952. PubMed id: 7681364
07-Mar-94     Release date:   31-May-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P27986  (P85A_HUMAN) -  Phosphatidylinositol 3-kinase regulatory subunit alpha
724 a.a.
76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     phosphatidylinositol 3-kinase complex   1 term 
  Biochemical function     phosphatidylinositol 3-kinase regulator activity     1 term  


Cell 72:945-952 (1993)
PubMed id: 7681364  
Structure of the PI3K SH3 domain and analysis of the SH3 family.
S.Koyama, H.Yu, D.C.Dalgarno, T.B.Shin, L.D.Zydowsky, S.L.Schreiber.
Src homology 3 (SH3) domains, which are found in many proteins involved in intracellular signal transduction, mediate specific protein-protein interactions. The three-dimensional structure of the SH3 domain in the p85 subunit of the phosphatidylinositol 3-kinase (PI3K) has been determined by multidimensional NMR methods. The molecule consists of four short helices, two beta turns, and two antiparallel beta sheets. The beta sheets are highly similar to corresponding regions in the SH3 domain of the tyrosine kinase Src, even though the sequence identity of the two domains is low. There is a unique 15 amino acid insert in PI3K that contains three short helices. There are substantial differences in the identity of the amino acids that make up the receptor site of SH3 domains. The results suggest that while the overall structures of the binding sites in the PI3K and Src SH3 domains are similar, their ligand binding properties may differ.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19919182 R.Batra-Safferling, J.Granzin, S.Mödder, S.Hoffmann, and D.Willbold (2010).
Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding.
  Biol Chem, 391, 33-42.
PDB codes: 3i5r 3i5s
19915146 H.Wu, S.C.Shekar, R.J.Flinn, M.El-Sibai, B.S.Jaiswal, K.I.Sen, V.Janakiraman, S.Seshagiri, G.J.Gerfen, M.E.Girvin, and J.M.Backer (2009).
Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110alpha and are disrupted in oncogenic p85 mutants.
  Proc Natl Acad Sci U S A, 106, 20258-20263.  
18537543 V.N.Uversky (2008).
Amyloidogenesis of natively unfolded proteins.
  Curr Alzheimer Res, 5, 260-287.  
17010654 N.Dimasi (2007).
Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction.
  Int J Biochem Cell Biol, 39, 109-123.
PDB code: 2d0n
16135792 S.Y.Ren, E.Bolton, M.G.Mohi, A.Morrione, B.G.Neel, and T.Skorski (2005).
Phosphatidylinositol 3-kinase p85{alpha} subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences.
  Mol Cell Biol, 25, 8001-8008.  
11536355 B.P.Krueger, and P.A.Kollman (2001).
Molecular dynamics simulations of a highly charged peptide from an SH3 domain: possible sequence-function relationship.
  Proteins, 45, 4.  
11141062 N.Okishio, T.Tanaka, R.Fukuda, and M.Nagai (2001).
Role of the conserved acidic residue Asp21 in the structure of phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and nuclear magnetic resonance studies.
  Biochemistry, 40, 119-129.  
10861385 N.Okishio, M.Nagai, R.Fukuda, S.Nagatomo, and T.Kitagawa (2000).
Interactions of phosphatidylinositol 3-kinase Src homology 3 domain with its ligand peptide studied by absorption, circular dichroism, and UV resonance raman spectroscopies.
  Biopolymers, 57, 208-217.  
10933808 R.Kleene, B.Classen, J.Zdzieblo, and M.Schrader (2000).
SH3 binding sites of ZG29p mediate an interaction with amylase and are involved in condensation-sorting in the exocrine rat pancreas.
  Biochemistry, 39, 9893-9900.  
10805734 Z.S.Zhao, E.Manser, and L.Lim (2000).
Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation.
  Mol Cell Biol, 20, 3906-3917.  
9539718 J.I.Guijarro, M.Sunde, J.A.Jones, I.D.Campbell, and C.M.Dobson (1998).
Amyloid fibril formation by an SH3 domain.
  Proc Natl Acad Sci U S A, 95, 4224-4228.  
9485402 K.W.Plaxco, J.I.Guijarro, C.J.Morton, M.Pitkeathly, I.D.Campbell, and C.M.Dobson (1998).
The folding kinetics and thermodynamics of the Fyn-SH3 domain.
  Biochemistry, 37, 2529-2537.  
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.  
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.  
9334745 D.S.Riddle, J.V.Santiago, S.T.Bray-Hall, N.Doshi, V.P.Grantcharova, Q.Yi, and D.Baker (1997).
Functional rapidly folding proteins from simplified amino acid sequences.
  Nat Struct Biol, 4, 805-809.  
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.  
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.  
9326643 M.I.Wahl, A.C.Fluckiger, R.M.Kato, H.Park, O.N.Witte, and D.J.Rawlings (1997).
Phosphorylation of two regulatory tyrosine residues in the activation of Bruton's tyrosine kinase via alternative receptors.
  Proc Natl Acad Sci U S A, 94, 11526-11533.  
9704065 M.Thelen, and S.A.Didichenko (1997).
G-protein coupled receptor-mediated activation of PI 3-kinase in neutrophils.
  Ann N Y Acad Sci, 832, 368-382.  
8619552 E.J.Dropcho (1996).
Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis.
  Ann Neurol, 39, 659-667.  
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.  
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.  
8807900 S.Feng, T.M.Kapoor, F.Shirai, A.P.Combs, and S.L.Schreiber (1996).
Molecular basis for the binding of SH3 ligands with non-peptide elements identified by combinatorial synthesis.
  Chem Biol, 3, 661-670.
PDB codes: 1nlo 1nlp
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.  
7775428 K.Watanabe, T.Fukuchi, H.Hosoya, T.Shirasawa, K.Matuoka, H.Miki, and T.Takenawa (1995).
Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms.
  J Biol Chem, 270, 13733-13739.  
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.  
7592689 P.Xu, A.S.Zot, and H.G.Zot (1995).
Identification of Acan125 as a myosin-I-binding protein present with myosin-I on cellular organelles of Acanthamoeba.
  J Biol Chem, 270, 25316-25319.  
7598957 S.A.Benner (1995).
Predicting the conformation of proteins from sequences. Progress and future progress.
  J Mol Recognit, 8, 9.  
8618911 S.Feng, C.Kasahara, R.J.Rickles, and S.L.Schreiber (1995).
Specific interactions outside the proline-rich core of two classes of Src homology 3 ligands.
  Proc Natl Acad Sci U S A, 92, 12408-12415.
PDB codes: 1qwe 1qwf
7538439 T.Li, S.Tsukada, A.Satterthwaite, M.H.Havlik, H.Park, K.Takatsu, and O.N.Witte (1995).
Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain.
  Immunity, 2, 451-460.  
  7781603 T.Raabe, J.P.Olivier, B.Dickson, X.Liu, G.D.Gish, T.Pawson, and E.Hafen (1995).
Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
  EMBO J, 14, 2509-2518.  
7657668 W.Yang, S.N.Malek, and S.Desiderio (1995).
An SH3-binding site conserved in Bruton's tyrosine kinase and related tyrosine kinases mediates specific protein interactions in vitro and in vivo.
  J Biol Chem, 270, 20832-20840.  
7499280 X.Y.Wang, D.K.Fuhrer, M.S.Marshall, and Y.C.Yang (1995).
Interleukin-11 induces complex formation of Grb2, Fyn, and JAK2 in 3T3L1 cells.
  J Biol Chem, 270, 27999-28002.  
8590002 Y.Q.Gosser, J.Zheng, M.Overduin, B.J.Mayer, and D.Cowburn (1995).
The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct.
  Structure, 3, 1075-1086.
PDB code: 1awo
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.  
  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
8166672 G.C.Prendergast, and J.B.Gibbs (1994).
Ras regulatory interactions: novel targets for anti-cancer intervention?
  Bioessays, 16, 187-191.  
7634092 H.Baumann, S.Knapp, T.Lundbäck, R.Ladenstein, and T.Härd (1994).
Solution structure and DNA-binding properties of a thermostable protein from the archaeon Sulfolobus solfataricus.
  Nat Struct Biol, 1, 808-819.
PDB code: 1sso
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.  
  8264609 K.H.Holt, L.Olson, W.S.Moye-Rowley, and J.E.Pessin (1994).
Phosphatidylinositol 3-kinase activation is mediated by high-affinity interactions between distinct domains within the p110 and p85 subunits.
  Mol Cell Biol, 14, 42-49.  
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.  
  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.  
15335710 T.Pawson, and J.Schlessingert (1993).
SH2 and SH3 domains.
  Curr Biol, 3, 434-442.  
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