CPLM-000918

Genbank Nucleotide ID

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

Protein Synonyms/Alias

PIP5K1-gamma; PtdIns(4)P-5-kinase 1 gamma; Phosphatidylinositol 4-phosphate 5-kinase type I gamma; PIP5KIgamma

Homo sapiens (Human)

Position	Peptide	Type	References
97	TVGHLSSKPERDVLM	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
345	AQSTSDEKRPVGQKA	ubiquitination	[6, 8]
351	EKRPVGQKALYSTAM	ubiquitination	[7]
414	KKLEHTWKALVHDGD	ubiquitination	[1]

[1] A data set of human endogenous protein ubiquitination sites.
Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
[2] 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]
[3] 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]
[4] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[5] 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]
[6] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[7] 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]
[8] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[9] 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]
[10] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

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 vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth.

DOMAIN 75 443 PIPK.
REGION 641 668 Mediates interaction with TLN2.
MOD_RES 265 265 N6-acetyllysine.
MOD_RES 268 268 N6-acetyllysine.
MOD_RES 639 639 Phosphotyrosine; by EGFR (By similarity).
MOD_RES 649 649 Phosphotyrosine; by CSK.
MOD_RES 650 650 Phosphoserine; by CDK5, MAPK1 and CDK1.

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell adhesion; Cell junction; Cell membrane; Cell projection; Chemotaxis; Complete proteome; Cytoplasm; Disease mutation; Endocytosis; Exocytosis; Kinase; Membrane; Nucleotide-binding; Nucleus; Phagocytosis; Phosphoprotein; Reference proteome; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
GO:0005925; C:focal adhesion; TAS:UniProtKB.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
GO:0001931; C:uropod; TAS:UniProtKB.
GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IEA:EC.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0030036; P:actin cytoskeleton organization; TAS:UniProtKB.
GO:0034333; P:adherens junction assembly; TAS:UniProtKB.
GO:0007411; P:axon guidance; TAS:Reactome.
GO:0016337; P:cell-cell adhesion; TAS:UniProtKB.
GO:0072583; P:clathrin-mediated endocytosis; TAS:UniProtKB.
GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
GO:0006909; P:phagocytosis; TAS:UniProtKB.
GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
GO:0046854; P:phosphatidylinositol phosphorylation; IEA:GOC.
GO:0044281; P:small molecule metabolic process; TAS:Reactome.
GO:0048488; P:synaptic vesicle endocytosis; TAS:UniProtKB.
GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB.

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.