CPLM-019785

Genbank Nucleotide ID

Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha

Protein Synonyms/Alias

PIP5K1-alpha; PtdIns(4)P-5-kinase 1 alpha; 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha; Phosphatidylinositol 4-phosphate 5-kinase type I alpha; PIP5KIalpha

Homo sapiens (Human)

Position	Peptide	Type	References
79	SGETTYKKTTSSALK	ubiquitination	[1]
103	TVGSLSTKPERDVLM	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
206	KEAEFLQKLLPGYYM	ubiquitination	[6, 9]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry.
Meierhofer D, Wang X, Huang L, Kaiser P.
J Proteome Res. 2008 Oct;7(10):4566-76. [PMID: 18781797]
[3] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[4] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[9] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

Catalyzes the phosphorylation of phosphatidylinositol 4- phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as actin cytoskeleton organization, cell adhesion, migration and phagocytosis. Required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of RAC1 to the plasma membrane. Together with PIP5K1C is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle ingestion by activating WAS that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B is required after stimulation of G-protein coupled receptors for stable platelet adhesion. Plays a role during calcium-induced keratinocyte differentiation. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate that mobilize internal calcium and drive keratinocyte differentiation. Together with PIP5K1C have a role during embryogenesis. Functions also in the nucleus where acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs.

DOMAIN 81 449 PIPK.
CROSSLNK 103 103 Glycyl lysine isopeptide (Lys-Gly)

Alternative splicing; ATP-binding; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Nucleus; Reference proteome; Transferase; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0030027; C:lamellipodium; IDA:UniProtKB.
GO:0016607; C:nuclear speck; IDA:UniProtKB.
GO:0032587; C:ruffle membrane; IDA:UniProtKB.
GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0019900; F:kinase binding; IDA:UniProtKB.
GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
GO:0032863; P:activation of Rac GTPase activity; IMP:UniProtKB.
GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
GO:0010761; P:fibroblast migration; IEA:Compara.
GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
GO:0030216; P:keratinocyte differentiation; TAS:UniProtKB.
GO:0006909; P:phagocytosis; TAS:UniProtKB.
GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
GO:0072661; P:protein targeting to plasma membrane; IMP:UniProtKB.
GO:0097178; P:ruffle assembly; IMP:UniProtKB.
GO:0007165; P:signal transduction; TAS:ProtInc.
GO:0044281; P:small molecule metabolic process; TAS:Reactome.

IPR023610; PInositol-4-P-5-kinase.
IPR027483; PInositol-4-P-5-kinase_C.
IPR002498; PInositol-4-P-5-kinase_core.
IPR027484; PInositol-4-P-5-kinase_N.
IPR016034; PInositol-4P-5-kinase_core_sub.