EzCatDB: D00116
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DB codeD00116
RLCP classification3.103.70035.351 : Transfer
CATH domainDomain 13.30.800.10 : Phosphatidylinositol Phosphate Kinase II BetaCatalytic domain
Domain 23.30.810.10 : Phosphatidylinositol Phosphate Kinase Iibeta; ChainCatalytic domain
E.C.2.7.1.149
CSA1bo1


Enzyme Name
UniProtKBKEGG

P78356
Protein namePhosphatidylinositol 5-phosphate 4-kinase type-2 beta1-phosphatidylinositol-5-phosphate 4-kinase
type II PIP kinase
SynonymsEC 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
RefSeqNP_003550.1 (Protein)
NM_003559.4 (DNA/RNA sequence)
PfamPF01504 (PIP5K)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00562Inositol phosphate metabolism
MAP04070Phosphatidylinositol signaling system

UniProtKB:Accession NumberP78356
Entry namePI42B_HUMAN
ActivityATP + 1-phosphatidyl-1D-myo-inositol 5- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
SubunitHomodimer. Binds TNFRSF1A.
Subcellular locationEndoplasmic 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).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C11557C00008C04637
CompoundMagnesiumATP1-Phosphatidyl-1D-myo-inositol 5-phosphateADP1-Phosphatidyl-1D-myo-inositol 4,5-bisphosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidecarbohydrate,lipid,phosphate group/phosphate ionamine group,nucleotidecarbohydrate,lipid,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1bo1A01UnboundUnboundUnboundUnboundUnbound
1bo1B01UnboundUnboundUnboundUnboundUnbound
1bo1A02UnboundUnboundUnboundUnboundUnbound
1bo1B02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [4], [10], [12]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1bo1A01LYS 150
 
       ;       
invisible 133-136
1bo1B01LYS 150
 
GLY 133;GLY 136
 
1bo1A02LYS 218;ASP 278
SER 280;ASP 369(Magnesium binding)
 
invisible 307-341, 373-390
1bo1B02LYS 218;ASP 278
SER 280;ASP 369(Magnesium binding)
 
invisible 304-342, 373-396

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID7768349
JournalFASEB J
Year1995
Volume9
Pages576-96
AuthorsHanks SK, Hunter T
TitleProtein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
[2]
PubMed ID8869744
JournalAdv Enzyme Regul
Year1996
Volume36
Pages115-40
AuthorsLoijens JC, Boronenkov IV, Parker GJ, Anderson RA
TitleThe phosphatidylinositol 4-phosphate 5-kinase family.
[3]
CommentsX-ray crystallography
PubMed ID9003756
JournalEMBO J
Year1996
Volume15
Pages6810-21
AuthorsKobe B, Heierhorst J, Feil SC, Parker MW, Benian GM, Weiss KR, Kemp BE
TitleGiant protein kinases: domain interactions and structural basis of autoregulation.
Related PDB1koa
[4]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-416, AND HOMODIMERIZATION.
PubMed ID9753329
JournalCell
Year1998
Volume94
Pages829-39
AuthorsRao VD, Misra S, Boronenkov IV, Anderson RA, Hurley JH
TitleStructure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.
Related PDB1bo1
Related UniProtKBP78356
[5]
PubMed ID10187762
JournalJ Biol Chem
Year1999
Volume274
Pages9907-10
AuthorsAnderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC
TitlePhosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes.
[6]
PubMed ID10438618
JournalJ Mol Biol
Year1999
Volume291
Pages239-47
AuthorsGrishin NV
TitlePhosphatidylinositol phosphate kinase: a link between protein kinase and glutathione synthase folds.
[7]
PubMed ID10678164
JournalMol Cell
Year2000
Volume5
Pages1-11
AuthorsKunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA
TitleThe activation loop of phosphatidylinositol phosphate kinases determines signaling specificity.
[8]
PubMed ID14502432
JournalJ Membr Biol
Year2003
Volume194
Pages77-89
AuthorsDoughman RL, Firestone AJ, Anderson RA
TitlePhosphatidylinositol phosphate kinases put PI4,5P(2) in its place.
[9]
PubMed ID15464023
JournalEur J Pharmacol
Year2004
Volume500
Pages87-99
AuthorsOude Weernink PA, Schmidt M, Jakobs KH
TitleRegulation and cellular roles of phosphoinositide 5-kinases.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 197-461 IN COMPLEX WITH SUBSTRATE AND ADP.
PubMed ID15350214
JournalMol Cell
Year2004
Volume15
Pages689-701
AuthorsGonzalez B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL
TitleStructure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase.
Related PDB1w2c,1w2d,1w2f
Related UniProtKBP23677
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 185-459 IN COMPLEX WITH ADP.
PubMed ID15350215
JournalMol Cell
Year2004
Volume15
Pages703-11
AuthorsMiller GJ, Hurley JH
TitleCrystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase.
Related PDB1tzd
Related UniProtKBP17105
[12]
PubMed ID15771780
JournalBMC Struct Biol
Year2005
Volume5
Pages6
AuthorsCheek S, Ginalski K, Zhang H, Grishin NV
TitleA comprehensive update of the sequence and structure classification of kinases.

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.

createdupdated
2007-03-192009-02-26


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