DB code: D00116

RLCP classification 3.103.70035.351 : Transfer
CATH domain 3.30.800.10 : Phosphatidylinositol Phosphate Kinase II Beta Catalytic domain
3.30.810.10 : Phosphatidylinositol Phosphate Kinase Iibeta; Chain Catalytic domain
E.C. 2.7.1.149
CSA 1bo1
M-CSA 1bo1
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P78356 Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
EC 2.7.1.149
1-phosphatidylinositol 5-phosphate 4-kinase 2-beta
Diphosphoinositide kinase 2-beta
Phosphatidylinositol 5-phosphate 4-kinase type II beta
PI(5)P 4-kinase type II beta
PIP4KII-beta
PtdIns(5)P-4-kinase isoform 2-beta
NP_003550.1 (Protein)
NM_003559.4 (DNA/RNA sequence)
PF01504 (PIP5K)
[Graphical View]

KEGG enzyme name
1-phosphatidylinositol-5-phosphate 4-kinase
type II PIP kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P78356 PI42B_HUMAN ATP + 1-phosphatidyl-1D-myo-inositol 5- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. Homodimer. Binds TNFRSF1A. Endoplasmic reticulum membrane, Peripheral membrane protein (By similarity). Cell membrane, Peripheral membrane protein (By similarity). Note=Associated with the plasma membrane and the endoplasmic reticulum (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP04070 Phosphatidylinositol signaling system
MAP00562 Inositol phosphate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C11557 C00008 C04637
E.C.
Compound Magnesium ATP 1-Phosphatidyl-1D-myo-inositol 5-phosphate ADP 1-Phosphatidyl-1D-myo-inositol 4,5-bisphosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide carbohydrate,lipid,phosphate group/phosphate ion amine group,nucleotide carbohydrate,lipid,phosphate group/phosphate ion
ChEBI 18420
15422
16761
PubChem 888
5957
6022
1bo1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bo1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bo1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bo1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4], [10], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bo1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 150 ; invisible 133-136
1bo1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 150 GLY 133;GLY 136
1bo1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 218;ASP 278 SER 280;ASP 369(Magnesium binding) invisible 307-341, 373-390
1bo1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 218;ASP 278 SER 280;ASP 369(Magnesium binding) invisible 304-342, 373-396

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.588-592
[4]
p.832-835
[10]
p.697
[11]
p.705-709
[12]
p.9-12

References
[1]
Resource
Comments
Medline ID
PubMed ID 7768349
Journal FASEB J
Year 1995
Volume 9
Pages 576-96
Authors Hanks SK, Hunter T
Title Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8869744
Journal Adv Enzyme Regul
Year 1996
Volume 36
Pages 115-40
Authors Loijens JC, Boronenkov IV, Parker GJ, Anderson RA
Title The phosphatidylinositol 4-phosphate 5-kinase family.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9003756
Journal EMBO J
Year 1996
Volume 15
Pages 6810-21
Authors Kobe B, Heierhorst J, Feil SC, Parker MW, Benian GM, Weiss KR, Kemp BE
Title Giant protein kinases: domain interactions and structural basis of autoregulation.
Related PDB 1koa
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-416, AND HOMODIMERIZATION.
Medline ID
PubMed ID 9753329
Journal Cell
Year 1998
Volume 94
Pages 829-39
Authors Rao VD, Misra S, Boronenkov IV, Anderson RA, Hurley JH
Title Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.
Related PDB 1bo1
Related UniProtKB P78356
[5]
Resource
Comments
Medline ID
PubMed ID 10187762
Journal J Biol Chem
Year 1999
Volume 274
Pages 9907-10
Authors Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC
Title Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10438618
Journal J Mol Biol
Year 1999
Volume 291
Pages 239-47
Authors Grishin NV
Title Phosphatidylinositol phosphate kinase: a link between protein kinase and glutathione synthase folds.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10678164
Journal Mol Cell
Year 2000
Volume 5
Pages 1-11
Authors Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA
Title The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 14502432
Journal J Membr Biol
Year 2003
Volume 194
Pages 77-89
Authors Doughman RL, Firestone AJ, Anderson RA
Title Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15464023
Journal Eur J Pharmacol
Year 2004
Volume 500
Pages 87-99
Authors Oude Weernink PA, Schmidt M, Jakobs KH
Title Regulation and cellular roles of phosphoinositide 5-kinases.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 197-461 IN COMPLEX WITH SUBSTRATE AND ADP.
Medline ID
PubMed ID 15350214
Journal Mol Cell
Year 2004
Volume 15
Pages 689-701
Authors Gonzalez B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL
Title Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase.
Related PDB 1w2c 1w2d 1w2f
Related UniProtKB P23677
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 185-459 IN COMPLEX WITH ADP.
Medline ID
PubMed ID 15350215
Journal Mol Cell
Year 2004
Volume 15
Pages 703-11
Authors Miller GJ, Hurley JH
Title Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase.
Related PDB 1tzd
Related UniProtKB P17105
[12]
Resource
Comments
Medline ID
PubMed ID 15771780
Journal BMC Struct Biol
Year 2005
Volume 5
Pages 6
Authors Cheek S, Ginalski K, Zhang H, Grishin NV
Title A comprehensive update of the sequence and structure classification of kinases.
Related PDB
Related UniProtKB

Comments
This enzyme is homologous to protein kinase A (D00114 in EzCatDB).
Although this enzyme is classified as 1-Phosphatidylinositol-4-phosphate 5-kinase (E.C. 2.7.1.68), this enzyme should be classified as 1-phosphatidylinositol-5-phosphate 4-kinase (E.C. 2.7.1.149), according to the literature [4].
According to the literature [1], [4], [12], the reaction proceeds as follows:
(0) Magnesium ion, which is bound to Asp369, stabilizes the transferred group, gamma-phosphate of ATP, and the leaving group, alpha-phosphate of ATP, whereas Lys150 stabilizes the leaving groups, alpha- and beta-phosphate groups, along with mainchain amide groups of Gly133/Gly136.
(1) Asp278 acts as a general base to deprotonate and activate the acceptor group of 4-hydroxyl group of the substrate.
(2) The activated hydroxyl group makes a nucleophilic attack on the transferred group, gamma-phosphate group of ATP, leading to the transition state, which should be stabilized by Lys150, Lys218, Gly133/Gly136 and the magnesium ion.
(3) The gamma-phosphate group of ATP is transferred to the 4-hydroxyl group.

Created Updated
2007-03-19 2009-02-26