PI42B_HUMAN
ID PI42B_HUMAN Reviewed; 416 AA.
AC P78356; Q5U0E8; Q8TBP2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 beta {ECO:0000305};
DE EC=2.7.1.149 {ECO:0000305|PubMed:26774281};
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-beta;
DE AltName: Full=Diphosphoinositide kinase 2-beta;
DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II beta;
DE Short=PI(5)P 4-kinase type II beta;
DE Short=PIP4KII-beta;
DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-beta;
GN Name=PIP4K2B {ECO:0000312|HGNC:HGNC:8998}; Synonyms=PIP5K2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH
RP TNFRSF1A, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9038203; DOI=10.1074/jbc.272.9.5861;
RA Castellino A.M., Parker G.J., Boronenkov I.V., Anderson R.A., Chao M.V.;
RT "A novel interaction between the juxtamembrane region of the p55 tumor
RT necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase.";
RL J. Biol. Chem. 272:5861-5870(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-150, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH PIP4K2A, SUBCELLULAR
RP LOCATION, UBIQUITINATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20583997; DOI=10.1042/bj20100341;
RA Bultsma Y., Keune W.-J., Divecha N.;
RT "PIP4Kbeta interacts with and modulates nuclear localization of the high-
RT activity PtdIns5P-4-kinase isoform PIP4Kalpha.";
RL Biochem. J. 430:223-235(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [11]
RP FUNCTION.
RX PubMed=31091439; DOI=10.1016/j.celrep.2019.04.070;
RA Wang D.G., Paddock M.N., Lundquist M.R., Sun J.Y., Mashadova O.,
RA Amadiume S., Bumpus T.W., Hodakoski C., Hopkins B.D., Fine M., Hill A.,
RA Yang T.J., Baskin J.M., Dow L.E., Cantley L.C.;
RT "PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent
RT Mechanism.";
RL Cell Rep. 27:1991.e5-2001.e5(2019).
RN [12] {ECO:0007744|PDB:1BO1}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-416, AND HOMODIMERIZATION.
RX PubMed=9753329; DOI=10.1016/s0092-8674(00)81741-9;
RA Rao V.D., Misra S., Boronenkov I.V., Anderson R.A., Hurley J.H.;
RT "Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein
RT kinase fold flattened for interfacial phosphorylation.";
RL Cell 94:829-839(1998).
RN [13] {ECO:0007744|PDB:3WZZ, ECO:0007744|PDB:3X01, ECO:0007744|PDB:3X05, ECO:0007744|PDB:3X06, ECO:0007744|PDB:3X07, ECO:0007744|PDB:3X08, ECO:0007744|PDB:3X09, ECO:0007744|PDB:3X0A, ECO:0007744|PDB:3X0B, ECO:0007744|PDB:3X0C}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 31-416 OF WILD-TYPE APOENZYME AND
RP IN COMPLEXES WITH ATP ANALOG; GTP ANALOG; AMP AND GMP AND MUTANTS MET-201;
RP LEU-205 AND ALA-368 IN COMPLEXES WITH AMP AND GMP, FUNCTION, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26774281; DOI=10.1016/j.molcel.2015.12.011;
RA Sumita K., Lo Y.H., Takeuchi K., Senda M., Kofuji S., Ikeda Y.,
RA Terakawa J., Sasaki M., Yoshino H., Majd N., Zheng Y., Kahoud E.R.,
RA Yokota T., Emerling B.M., Asara J.M., Ishida T., Locasale J.W., Daikoku T.,
RA Anastasiou D., Senda T., Sasaki A.T.;
RT "The Lipid Kinase PI5P4Kbeta Is an Intracellular GTP Sensor for Metabolism
RT and Tumorigenesis.";
RL Mol. Cell 61:187-198(2016).
CC -!- FUNCTION: Participates in the biosynthesis of phosphatidylinositol 4,5-
CC bisphosphate (PubMed:9038203, PubMed:26774281). Preferentially utilizes
CC GTP, rather than ATP, for PI(5)P phosphorylation and its activity
CC reflects changes in direct proportion to the physiological GTP
CC concentration (PubMed:26774281). Its GTP-sensing activity is critical
CC for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate
CC insulin signaling through a catalytic-independent mechanism. They
CC interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2
CC synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3
CC (PubMed:31091439). {ECO:0000269|PubMed:26774281,
CC ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:9038203}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:12280,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57795,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.149;
CC Evidence={ECO:0000305|PubMed:26774281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281;
CC Evidence={ECO:0000305|PubMed:26774281};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83423,
CC ChEBI:CHEBI:84968, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26774281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993;
CC Evidence={ECO:0000305|PubMed:26774281};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + GTP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + GDP + H(+); Xref=Rhea:RHEA:55964,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:83423, ChEBI:CHEBI:84968;
CC Evidence={ECO:0000269|PubMed:26774281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965;
CC Evidence={ECO:0000305|PubMed:26774281};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for phosphatidylinositol-5- phosphate
CC {ECO:0000269|PubMed:20583997};
CC KM=88 uM for ATP {ECO:0000269|PubMed:26774281};
CC KM=236 uM for GTP {ECO:0000269|PubMed:26774281};
CC Vmax=0.2 pmol/min/ug enzyme {ECO:0000269|PubMed:20583997};
CC Vmax=57 umol/min/mg enzyme toward ATP {ECO:0000269|PubMed:26774281};
CC Vmax=88 umol/min/mg enzyme toward GTP {ECO:0000269|PubMed:26774281};
CC -!- SUBUNIT: Homodimer. Binds TNFRSF1A (PubMed:9038203). Interacts with
CC PIP4K2A; the interaction suppresses ubiquitination by the SPOP/CUL3
CC complex (PubMed:20583997). {ECO:0000269|PubMed:20583997,
CC ECO:0000269|PubMed:9038203}.
CC -!- INTERACTION:
CC P78356; Q6NT76: HMBOX1; NbExp=5; IntAct=EBI-947090, EBI-2549423;
CC P78356-2; Q96GN5: CDCA7L; NbExp=3; IntAct=EBI-11532361, EBI-5278764;
CC P78356-2; P68400: CSNK2A1; NbExp=3; IntAct=EBI-11532361, EBI-347804;
CC P78356-2; Q9UBY9: HSPB7; NbExp=3; IntAct=EBI-11532361, EBI-739361;
CC P78356-2; Q9C086: INO80B; NbExp=3; IntAct=EBI-11532361, EBI-715611;
CC P78356-2; Q16719-2: KYNU; NbExp=3; IntAct=EBI-11532361, EBI-12351611;
CC P78356-2; P40692: MLH1; NbExp=3; IntAct=EBI-11532361, EBI-744248;
CC P78356-2; O43395: PRPF3; NbExp=3; IntAct=EBI-11532361, EBI-744322;
CC P78356-2; P20618: PSMB1; NbExp=3; IntAct=EBI-11532361, EBI-372273;
CC P78356-2; Q9NQG5: RPRD1B; NbExp=3; IntAct=EBI-11532361, EBI-747925;
CC P78356-2; P52739-2: ZNF131; NbExp=3; IntAct=EBI-11532361, EBI-10213055;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000269|PubMed:20583997}. Cytoplasm {ECO:0000269|PubMed:20583997}.
CC Note=Associated with the plasma membrane and the endoplasmic reticulum.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78356-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78356-2; Sequence=VSP_010384, VSP_010385;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, pancreas,
CC skeletal muscle and kidney. Detected at lower levels in placenta, lung
CC and liver. {ECO:0000269|PubMed:9038203}.
CC -!- PTM: Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is
CC stimulated by PtdIns5P levels. {ECO:0000269|PubMed:20583997}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000269|PubMed:19369195}.
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DR EMBL; U85245; AAB48596.1; -; mRNA.
DR EMBL; BT019614; AAV38420.1; -; mRNA.
DR EMBL; BC027459; AAH27459.1; -; mRNA.
DR CCDS; CCDS11329.1; -. [P78356-1]
DR RefSeq; NP_003550.1; NM_003559.4. [P78356-1]
DR PDB; 1BO1; X-ray; 3.00 A; A/B=1-416.
DR PDB; 3WZZ; X-ray; 2.60 A; A/B=31-416.
DR PDB; 3X01; X-ray; 2.15 A; A/B=31-416.
DR PDB; 3X02; X-ray; 2.45 A; A/B=31-416.
DR PDB; 3X03; X-ray; 2.70 A; A/B=31-416.
DR PDB; 3X04; X-ray; 2.60 A; A/B=31-416.
DR PDB; 3X05; X-ray; 2.50 A; A/B=31-416.
DR PDB; 3X06; X-ray; 2.65 A; A/B=31-416.
DR PDB; 3X07; X-ray; 2.60 A; A/B=31-416.
DR PDB; 3X08; X-ray; 2.75 A; A/B=31-416.
DR PDB; 3X09; X-ray; 2.70 A; A/B=31-416.
DR PDB; 3X0A; X-ray; 2.60 A; A/B=31-416.
DR PDB; 3X0B; X-ray; 2.60 A; A/B=31-416.
DR PDB; 3X0C; X-ray; 2.55 A; A/B=31-416.
DR PDB; 6K4G; X-ray; 2.70 A; A/B=31-416.
DR PDB; 6K4H; X-ray; 2.55 A; A/B=31-416.
DR PDB; 7EM1; X-ray; 2.65 A; A/B=31-416.
DR PDB; 7EM2; X-ray; 2.60 A; A/B=31-416.
DR PDB; 7EM3; X-ray; 3.10 A; A/B=31-416.
DR PDB; 7EM4; X-ray; 2.80 A; A/B=31-416.
DR PDB; 7EM5; X-ray; 2.80 A; A/B=31-416.
DR PDB; 7EM6; X-ray; 2.95 A; A/B=31-416.
DR PDB; 7EM7; X-ray; 3.45 A; A/B=31-416.
DR PDB; 7EM8; X-ray; 3.05 A; A/B=31-416.
DR PDB; 7N80; X-ray; 2.50 A; A/B=32-416.
DR PDB; 7N81; X-ray; 2.70 A; A/B=32-416.
DR PDBsum; 1BO1; -.
DR PDBsum; 3WZZ; -.
DR PDBsum; 3X01; -.
DR PDBsum; 3X02; -.
DR PDBsum; 3X03; -.
DR PDBsum; 3X04; -.
DR PDBsum; 3X05; -.
DR PDBsum; 3X06; -.
DR PDBsum; 3X07; -.
DR PDBsum; 3X08; -.
DR PDBsum; 3X09; -.
DR PDBsum; 3X0A; -.
DR PDBsum; 3X0B; -.
DR PDBsum; 3X0C; -.
DR PDBsum; 6K4G; -.
DR PDBsum; 6K4H; -.
DR PDBsum; 7EM1; -.
DR PDBsum; 7EM2; -.
DR PDBsum; 7EM3; -.
DR PDBsum; 7EM4; -.
DR PDBsum; 7EM5; -.
DR PDBsum; 7EM6; -.
DR PDBsum; 7EM7; -.
DR PDBsum; 7EM8; -.
DR PDBsum; 7N80; -.
DR PDBsum; 7N81; -.
DR AlphaFoldDB; P78356; -.
DR SMR; P78356; -.
DR BioGRID; 113985; 72.
DR IntAct; P78356; 38.
DR MINT; P78356; -.
DR STRING; 9606.ENSP00000482548; -.
DR BindingDB; P78356; -.
DR ChEMBL; CHEMBL5667; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P78356; -.
DR SwissLipids; SLP:000001885; -.
DR GlyGen; P78356; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P78356; -.
DR PhosphoSitePlus; P78356; -.
DR BioMuta; PIP4K2B; -.
DR DMDM; 47605991; -.
DR EPD; P78356; -.
DR jPOST; P78356; -.
DR MassIVE; P78356; -.
DR MaxQB; P78356; -.
DR PaxDb; P78356; -.
DR PeptideAtlas; P78356; -.
DR PRIDE; P78356; -.
DR ProteomicsDB; 57586; -. [P78356-1]
DR ProteomicsDB; 57587; -. [P78356-2]
DR Antibodypedia; 72369; 188 antibodies from 25 providers.
DR DNASU; 8396; -.
DR Ensembl; ENST00000613180.2; ENSP00000480776.1; ENSG00000277292.2. [P78356-1]
DR Ensembl; ENST00000619039.5; ENSP00000482548.1; ENSG00000276293.5. [P78356-1]
DR GeneID; 8396; -.
DR KEGG; hsa:8396; -.
DR MANE-Select; ENST00000619039.5; ENSP00000482548.1; NM_003559.5; NP_003550.1.
DR UCSC; uc002hqs.4; human. [P78356-1]
DR CTD; 8396; -.
DR DisGeNET; 8396; -.
DR GeneCards; PIP4K2B; -.
DR HGNC; HGNC:8998; PIP4K2B.
DR HPA; ENSG00000276293; Low tissue specificity.
DR MIM; 603261; gene.
DR neXtProt; NX_P78356; -.
DR OpenTargets; ENSG00000276293; -.
DR PharmGKB; PA162399640; -.
DR VEuPathDB; HostDB:ENSG00000276293; -.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000159874; -.
DR HOGENOM; CLU_004312_7_0_1; -.
DR InParanoid; P78356; -.
DR OMA; MKSHENA; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; P78356; -.
DR TreeFam; TF354315; -.
DR BRENDA; 2.7.1.149; 2681.
DR PathwayCommons; P78356; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8847453; Synthesis of PIPs in the nucleus.
DR SABIO-RK; P78356; -.
DR SignaLink; P78356; -.
DR SIGNOR; P78356; -.
DR BioGRID-ORCS; 8396; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; PIP4K2B; human.
DR EvolutionaryTrace; P78356; -.
DR GeneWiki; PIP4K2B; -.
DR GenomeRNAi; 8396; -.
DR Pharos; P78356; Tchem.
DR PRO; PR:P78356; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P78356; protein.
DR Bgee; ENSG00000276293; Expressed in cortical plate and 97 other tissues.
DR ExpressionAtlas; P78356; baseline and differential.
DR Genevisible; P78356; HS.
DR GO; GO:0005776; C:autophagosome; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB.
DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:1902635; P:1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0090217; P:negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity; IMP:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR DisProt; DP00054; -.
DR Gene3D; 3.30.800.10; -; 1.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell membrane; Cytoplasm; Endoplasmic reticulum; GTP-binding; Kinase;
KW Lipid metabolism; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..416
FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2
FT beta"
FT /id="PRO_0000185470"
FT DOMAIN 38..415
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 64..70
FT /note="Required for interaction with PIP5K1A"
FT /evidence="ECO:0000250|UniProtKB:Q8TBX8"
FT BINDING 202..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26774281,
FT ECO:0007744|PDB:3X03"
FT BINDING 203..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:26774281,
FT ECO:0007744|PDB:3X04"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26774281,
FT ECO:0007744|PDB:3X03"
FT BINDING 214
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:26774281,
FT ECO:0007744|PDB:3X04"
FT BINDING 369
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:26774281,
FT ECO:0007744|PDB:3X04"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 8
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 94
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 150
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80XI4"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT VAR_SEQ 270..281
FT /note="FLAQLKIMDYSL -> EILVLSPGRRIA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010384"
FT VAR_SEQ 282..416
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010385"
FT CONFLICT 250
FT /note="L -> P (in Ref. 2; AAV38420)"
FT /evidence="ECO:0000305"
FT HELIX 41..57
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 68..72
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 74..82
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:7N81"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 154..173
FT /evidence="ECO:0007829|PDB:3X01"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 183..191
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 194..202
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1BO1"
FT TURN 228..232
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 240..245
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 254..273
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 280..287
FT /evidence="ECO:0007829|PDB:3X01"
FT HELIX 288..303
FT /evidence="ECO:0007829|PDB:3X01"
FT TURN 344..346
FT /evidence="ECO:0007829|PDB:3X01"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:1BO1"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:1BO1"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:3X02"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1BO1"
FT HELIX 401..412
FT /evidence="ECO:0007829|PDB:3X01"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:3X02"
SQ SEQUENCE 416 AA; 47378 MW; 2288CD2883EACEBE CRC64;
MSSNCTSTTA VAVAPLSASK TKTKKKHFVC QKVKLFRASE PILSVLMWGV NHTINELSNV
PVPVMLMPDD FKAYSKIKVD NHLFNKENLP SRFKFKEYCP MVFRNLRERF GIDDQDYQNS
VTRSAPINSD SQGRCGTRFL TTYDRRFVIK TVSSEDVAEM HNILKKYHQF IVECHGNTLL
PQFLGMYRLT VDGVETYMVV TRNVFSHRLT VHRKYDLKGS TVAREASDKE KAKDLPTFKD
NDFLNEGQKL HVGEESKKNF LEKLKRDVEF LAQLKIMDYS LLVGIHDVDR AEQEEMEVEE
RAEDEECEND GVGGNLLCSY GTPPDSPGNL LSFPRFFGPG EFDPSVDVYA MKSHESSPKK
EVYFMAIIDI LTPYDTKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFNEF MSNILT
