PDBsum entry 1bo1

Go to PDB code: 
protein Protein-protein interface(s) links
Transferase PDB id
Protein chain
326 a.a. *
Waters ×19
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Phosphatidylinositol phosphate kinase type ii beta
Structure: Protein (phosphatidylinositol phosphate kinase iibeta). Chain: a, b. Synonym: pipk. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: bl21(de3). Other_details: human enzyme cloned into e.Coli.
Biol. unit: Dimer (from PQS)
3.00Å     R-factor:   0.229     R-free:   0.299
Authors: V.D.Rao,S.Misra,I.V.Boronenkov,R.A.Anderson,J.H.Hurley
Key ref:
V.D.Rao et al. (1998). Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation. Cell, 94, 829-839. PubMed id: 9753329 DOI: 10.1016/S0092-8674(00)81741-9
02-Aug-98     Release date:   07-Oct-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P78356  (PI42B_HUMAN) -  Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
416 a.a.
326 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 1-phosphatidylinositol-5-phosphate 4-kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

1-Phosphatidyl-myo-inositol Metabolism
      Reaction: ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate = ADP + 1-phosphatidyl- 1D-myo-inositol 4,5-bisphosphate
+ 1-phosphatidyl-1D-myo-inositol 5-phosphate
+ 1-phosphatidyl- 1D-myo-inositol 4,5-bisphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     intracellular signal transduction   8 terms 
  Biochemical function     nucleotide binding     8 terms  


DOI no: 10.1016/S0092-8674(00)81741-9 Cell 94:829-839 (1998)
PubMed id: 9753329  
Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.
V.D.Rao, S.Misra, I.V.Boronenkov, R.A.Anderson, J.H.Hurley.
Phosphoinositide kinases play central roles in signal transduction by phosphorylating the inositol ring at specific positions. The structure of one such enzyme, type IIbeta phosphatidylinositol phosphate kinase, reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to one superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 A basic flat face that suggests an electrostatic mechanism for plasma membrane targeting. Conserved basic residues form a putative phosphatidylinositol phosphate specificity site. The substrate-binding site is open on one side, consistent with dual specificity for phosphatidylinositol 3- and 5-phosphates. A modeled complex with membrane-bound substrate and ATP shows how a phosphoinositide kinase can phosphorylate its substrate in situ at the membrane interface.
  Selected figure(s)  
Figure 1.
Figure 1. Tertiary and Quaternary Structure of PIPKIIβ(A) Ribbon drawing of PIPKIIβ monomer prepared with MOLSCRIPT ([34]) and Raster3D ( [40]).(B) Schematic of the PIPKIIβ fold. The conserved ATP-binding core elements are colored green.(C) Ribbon representation of the PIPKIIβ dimer. The subunits are colored yellow (molecule A) and red (molecule B).
Figure 3.
Figure 3. Molecular Surface of the PIPKIIβ DimerThe surface is colored according to electrostatic potential using GRASP ([42]) in (A) sagittal and (B) normal projections relative to the presumed plane of the membrane. Saturating red indicated φ < −10 kT/e, and saturating blue indicates φ > 10 kT/e, where T = 293°K. ATP and the inositol (1,5) bisphosphate moiety of the PI5P headgroup are shown in yellow bonds docked into one of the two active sites. (C) Docking of PIPKIIβ dimer onto a membrane surface, using the DMPC crystal structure as a model. The asterisk and arrow indicate the putative TNF receptor–binding site.
  The above figures are reprinted by permission from Cell Press: Cell (1998, 94, 829-839) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21206902 D.S.Lieber, O.Elemento, and S.Tavazoie (2010).
Large-scale discovery and characterization of protein regulatory motifs in eukaryotes.
  PLoS One, 5, e14444.  
19896968 J.H.Clarke, M.Wang, and R.F.Irvine (2010).
Localization, regulation and function of Type II phosphatidylinositol 5-phosphate 4-kinases.
  Adv Enzyme Regul, 50, 12-18.  
20559679 K.Kwiatkowska (2010).
One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane.
  Cell Mol Life Sci, 67, 3927-3946.  
20525901 K.Ohshima, and K.Igarashi (2010).
Inference for the initial stage of domain shuffling: tracing the evolutionary fate of the PIPSL retrogene in hominoids.
  Mol Biol Evol, 27, 2522-2533.  
20066467 M.J.Schell (2010).
Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling.
  Cell Mol Life Sci, 67, 1755-1778.  
20569199 M.Wang, N.J.Bond, A.J.Letcher, J.P.Richardson, K.S.Lilley, R.F.Irvine, and J.H.Clarke (2010).
Genomic tagging reveals a random association of endogenous PtdIns5P 4-kinases IIalpha and IIbeta and a partial nuclear localization of the IIalpha isoform.
  Biochem J, 430, 215-221.  
20583997 Y.Bultsma, W.J.Keune, and N.Divecha (2010).
PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha.
  Biochem J, 430, 223-235.  
19951917 G.D.Fairn, K.Ogata, R.J.Botelho, P.D.Stahl, R.A.Anderson, P.De Camilli, T.Meyer, S.Wodak, and S.Grinstein (2009).
An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis.
  J Cell Biol, 187, 701-714.  
19580826 T.Sasaki, S.Takasuga, J.Sasaki, S.Kofuji, S.Eguchi, M.Yamazaki, and A.Suzuki (2009).
Mammalian phosphoinositide kinases and phosphatases.
  Prog Lipid Res, 48, 307-343.  
18050271 E.Szymańska, A.Sobota, E.Czuryło, and K.Kwiatkowska (2008).
Expression of PI(4,5)P(2)-binding proteins lowers the PI(4,5)P(2 )level and inhibits FcgammaRIIA-mediated cell spreading and phagocytosis.
  Eur J Immunol, 38, 260-272.  
18753295 J.H.Clarke, P.C.Emson, and R.F.Irvine (2008).
Localization of phosphatidylinositol phosphate kinase IIgamma in kidney to a membrane trafficking compartment within specialized cells of the nephron.
  Am J Physiol Renal Physiol, 295, F1422-F1430.  
17290217 A.Nakano-Kobayashi, M.Yamazaki, T.Unoki, T.Hongu, C.Murata, R.Taguchi, T.Katada, M.A.Frohman, T.Yokozeki, and Y.Kanaho (2007).
Role of activation of PIP5Kgamma661 by AP-2 complex in synaptic vesicle endocytosis.
  EMBO J, 26, 1105-1116.  
17623810 D.V.Babushok, K.Ohshima, E.M.Ostertag, X.Chen, Y.Wang, P.K.Mandal, N.Okada, C.S.Abrams, and H.H.Kazazian (2007).
A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids.
  Genome Res, 17, 1129-1138.  
17303380 J.P.Richardson, M.Wang, J.H.Clarke, K.J.Patel, and R.F.Irvine (2007).
Genomic tagging of endogenous type IIbeta phosphatidylinositol 5-phosphate 4-kinase in DT40 cells reveals a nuclear localisation.
  Cell Signal, 19, 1309-1314.  
16888807 M.Jarquin-Pardo, A.Fitzpatrick, F.J.Galiano, E.A.First, and J.N.Davis (2007).
Phosphatidic acid regulates the affinity of the murine phosphatidylinositol 4-phosphate 5-kinase-Ibeta for phosphatidylinositol-4-phosphate.
  J Cell Biochem, 100, 112-128.  
17382260 T.Strahl, and J.Thorner (2007).
Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae.
  Biochim Biophys Acta, 1771, 353-404.  
17520274 Y.S.Mao, and H.L.Yin (2007).
Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases.
  Pflugers Arch, 455, 5.  
16434494 H.Schulze, M.Korpal, J.Hurov, S.W.Kim, J.Zhang, L.C.Cantley, T.Graf, and R.A.Shivdasani (2006).
Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis.
  Blood, 107, 3868-3875.  
16563698 K.A.Hinchliffe, and R.F.Irvine (2006).
Regulation of type II PIP kinase by PKD phosphorylation.
  Cell Signal, 18, 1906-1913.  
16880396 M.Krauss, V.Kukhtina, A.Pechstein, and V.Haucke (2006).
Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes.
  Proc Natl Acad Sci U S A, 103, 11934-11939.  
16801950 S.G.Schwab, M.Knapp, P.Sklar, G.N.Eckstein, C.Sewekow, M.Borrmann-Hassenbach, M.Albus, T.Becker, J.F.Hallmayer, B.Lerer, W.Maier, and D.B.Wildenauer (2006).
Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.
  Mol Psychiatry, 11, 837-846.  
17050532 W.Holmes, and G.Jogl (2006).
Crystal structure of inositol phosphate multikinase 2 and implications for substrate specificity.
  J Biol Chem, 281, 38109-38116.
PDB codes: 2iew 2if8
16244704 E.D.Scheeff, and P.E.Bourne (2005).
Structural evolution of the protein kinase-like superfamily.
  PLoS Comput Biol, 1, e49.  
15613384 J.R.Bradford, and D.R.Westhead (2005).
Improved prediction of protein-protein binding sites using a support vector machines approach.
  Bioinformatics, 21, 1487-1494.  
16052242 M.R.Wenk (2005).
The emerging field of lipidomics.
  Nat Rev Drug Discov, 4, 594-610.  
15771780 S.Cheek, K.Ginalski, H.Zhang, and N.V.Grishin (2005).
A comprehensive update of the sequence and structure classification of kinases.
  BMC Struct Biol, 5, 6.  
15902656 S.Li, L.Tiab, X.Jiao, F.L.Munier, L.Zografos, B.E.Frueh, Y.Sergeev, J.Smith, B.Rubin, M.A.Meallet, R.K.Forster, J.F.Hejtmancik, and D.F.Schorderet (2005).
Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy.
  Am J Hum Genet, 77, 54-63.  
16365163 T.Strahl, H.Hama, D.B.DeWald, and J.Thorner (2005).
Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus.
  J Cell Biol, 171, 967-979.  
14701839 J.D.Chang, S.J.Field, L.E.Rameh, C.L.Carpenter, and L.C.Cantley (2004).
Identification and characterization of a phosphoinositide phosphate kinase homolog.
  J Biol Chem, 279, 11672-11679.  
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
12795693 J.D.Shaw, H.Hama, F.Sohrabi, D.B.DeWald, and B.Wendland (2003).
PtdIns(3,5)P2 is required for delivery of endocytic cargo into the multivesicular body.
  Traffic, 4, 479-490.  
12573692 J.H.Hurley (2003).
Membrane proteins: adapting to life at the interface.
  Chem Biol, 10, 2-3.  
12910457 S.Vucetic, C.J.Brown, A.K.Dunker, and Z.Obradovic (2003).
Flavors of protein disorder.
  Proteins, 52, 573-584.  
12215430 B.Barylko, P.Wlodarski, D.D.Binns, S.H.Gerber, S.Earnest, T.C.Sudhof, N.Grichine, and J.P.Albanesi (2002).
Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II.
  J Biol Chem, 277, 44366-44375.  
12191620 D.L.Burk, and A.M.Berghuis (2002).
Protein kinase inhibitors and antibiotic resistance.
  Pharmacol Ther, 93, 283-292.  
11891857 F.J.Galiano, E.T.Ulug, and J.N.Davis (2002).
Overexpression of murine phosphatidylinositol 4-phosphate 5-kinase type Ibeta disrupts a phosphatidylinositol 4,5 bisphosphate regulated endosomal pathway.
  J Cell Biochem, 85, 131-145.  
11733501 J.Kunz, A.Fuelling, L.Kolbe, and R.A.Anderson (2002).
Stereo-specific substrate recognition by phosphatidylinositol phosphate kinases is swapped by changing a single amino acid residue.
  J Biol Chem, 277, 5611-5619.  
12422220 K.Ling, R.L.Doughman, A.J.Firestone, M.W.Bunce, and R.A.Anderson (2002).
Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.
  Nature, 420, 89-93.  
11877391 M.Yamazaki, H.Miyazaki, H.Watanabe, T.Sasaki, T.Maehama, M.A.Frohman, and Y.Kanaho (2002).
Phosphatidylinositol 4-phosphate 5-kinase is essential for ROCK-mediated neurite remodeling.
  J Biol Chem, 277, 17226-17230.  
11714711 O.C.Ikonomov, D.Sbrissa, K.Mlak, M.Kanzaki, J.Pessin, and A.Shisheva (2002).
Functional dissection of lipid and protein kinase signals of PIKfyve reveals the role of PtdIns 3,5-P2 production for endomembrane integrity.
  J Biol Chem, 277, 9206-9211.  
12393916 S.M.Pitson, P.A.Moretti, J.R.Zebol, R.Zareie, C.K.Derian, A.L.Darrow, J.Qi, R.J.D'Andrea, C.J.Bagley, M.A.Vadas, and B.W.Wattenberg (2002).
The nucleotide-binding site of human sphingosine kinase 1.
  J Biol Chem, 277, 49545-49553.  
11514228 D.D.Boehr, W.S.Lane, and G.D.Wright (2001).
Active site labeling of the gentamicin resistance enzyme AAC(6')-APH(2") by the lipid kinase inhibitor wortmannin.
  Chem Biol, 8, 791-800.  
11311856 G.Vereb, A.Balla, P.Gergely, M.P.Wymann, H.Gülkan, S.Suer, and L.M.Heilmeyer (2001).
The ATP-binding site of brain phosphatidylinositol 4-kinase PI4K230 as revealed by 5'-p-fluorosulfonylbenzoyladenosine.
  Int J Biochem Cell Biol, 33, 249-259.  
11389851 H.Yamaguchi, M.Matsushita, A.C.Nairn, and J.Kuriyan (2001).
Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.
  Mol Cell, 7, 1047-1057.
PDB codes: 1ia9 1iah 1iaj
11468364 J.M.Higgins (2001).
Haspin-like proteins: a new family of evolutionarily conserved putative eukaryotic protein kinases.
  Protein Sci, 10, 1677-1684.  
11170411 L.Feng, M.Mejillano, H.L.Yin, J.Chen, and G.D.Prestwich (2001).
Full-contact domain labeling: identification of a novel phosphoinositide binding site on gelsolin that requires the complete protein.
  Biochemistry, 40, 904-913.  
11348594 Y.Tsujishita, S.Guo, L.E.Stolz, J.D.York, and J.H.Hurley (2001).
Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase.
  Cell, 105, 379-389.
PDB codes: 1i9y 1i9z
10673441 A.Dessen (2000).
Phospholipase A(2) enzymes: structural diversity in lipid messenger metabolism.
  Structure, 8, R15-R22.  
11123925 D.Sbrissa, O.C.Ikonomov, and A.Shisheva (2000).
PIKfyve lipid kinase is a protein kinase: downregulation of 5'-phosphoinositide product formation by autophosphorylation.
  Biochemistry, 39, 15980-15989.  
11114512 J.H.Hurley, Y.Tsujishita, and M.A.Pearson (2000).
Floundering about at cell membranes: a structural view of phospholipid signaling.
  Curr Opin Struct Biol, 10, 737-743.  
10678164 J.Kunz, M.P.Wilson, M.Kisseleva, J.H.Hurley, P.W.Majerus, and R.A.Anderson (2000).
The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity.
  Mol Cell, 5, 1.  
10870104 R.Eck, A.Bruckmann, R.Wetzker, and W.Künkel (2000).
A phosphatidylinositol 3-kinase of Candida albicans: molecular cloning and characterization.
  Yeast, 16, 933-944.  
10319815 A.Dessen, J.Tang, H.Schmidt, M.Stahl, J.D.Clark, J.Seehra, and W.S.Somers (1999).
Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism.
  Cell, 97, 349-360.
PDB code: 1cjy
9889150 D.M.Daigle, G.A.McKay, P.R.Thompson, and G.D.Wright (1999).
Aminoglycoside antibiotic phosphotransferases are also serine protein kinases.
  Chem Biol, 6, 11-18.  
10585939 D.Murray, A.Arbuzova, G.Hangyás-Mihályné, A.Gambhir, N.Ben-Tal, B.Honig, and S.McLaughlin (1999).
Electrostatic properties of membranes containing acidic lipids and adsorbed basic peptides: theory and experiment.
  Biophys J, 77, 3176-3188.  
10570119 G.D.Plowman, S.Sudarsanam, J.Bingham, D.Whyte, and T.Hunter (1999).
The protein kinases of Caenorhabditis elegans: a model for signal transduction in multicellular organisms.
  Proc Natl Acad Sci U S A, 96, 13603-13610.  
10508590 K.A.Hinchliffe, A.Ciruela, A.J.Letcher, N.Divecha, and R.F.Irvine (1999).
Regulation of type IIalpha phosphatidylinositol phosphate kinase localisation by the protein kinase CK2.
  Curr Biol, 9, 983-986.  
10574756 P.C.Driscoll, and A.L.Vuidepot (1999).
Peripheral membrane proteins: FYVE sticky fingers.
  Curr Biol, 9, R857-R860.  
10187762 R.A.Anderson, I.V.Boronenkov, S.D.Doughman, J.Kunz, and J.C.Loijens (1999).
Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes.
  J Biol Chem, 274, 9907-9910.  
10567352 R.K.McEwen, S.K.Dove, F.T.Cooke, G.F.Painter, A.B.Holmes, A.Shisheva, Y.Ohya, P.J.Parker, and R.H.Michell (1999).
Complementation analysis in PtdInsP kinase-deficient yeast mutants demonstrates that Schizosaccharomyces pombe and murine Fab1p homologues are phosphatidylinositol 3-phosphate 5-kinases.
  J Biol Chem, 274, 33905-33912.  
10367894 S.Misra, and J.H.Hurley (1999).
Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.
  Cell, 97, 657-666.
PDB code: 1vfy
10357805 S.Steinbacher, P.Hof, L.Eichinger, M.Schleicher, J.Gettemans, J.Vandekerckhove, R.Huber, and J.Benz (1999).
The crystal structure of the Physarum polycephalum actin-fragmin kinase: an atypical protein kinase with a specialized substrate-binding domain.
  EMBO J, 18, 2923-2929.
PDB code: 1cja
9838059 K.A.Hinchliffe, A.Ciruela, and R.F.Irvine (1998).
PIPkins1, their substrates and their products: new functions for old enzymes.
  Biochim Biophys Acta, 1436, 87.  
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.