PI42B_MOUSE
ID PI42B_MOUSE Reviewed; 416 AA.
AC Q80XI4; Q8VHB2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 beta {ECO:0000305};
DE EC=2.7.1.149 {ECO:0000250|UniProtKB:P78356};
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|MGI:MGI:1934234}; Synonyms=Pip5k2b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-416.
RC STRAIN=Swiss Webster / NIH;
RX PubMed=12438746; DOI=10.1159/000064062;
RA Kleiter N., Artner I., Gmachl N., Ghaffari-Tabrizi N., Kratochwil K.;
RT "Mutagenic transgene insertion into a region of high gene density and
RT multiple linkage disruptions on mouse chromosome 11.";
RL Cytogenet. Genome Res. 97:100-105(2002).
RN [3]
RP PROTEIN SEQUENCE OF 79-86; 110-123; 189-202; 267-275; 291-301 AND 389-405,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-322 AND SER-326, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=29727621; DOI=10.1016/j.molcel.2018.03.037;
RA Lundquist M.R., Goncalves M.D., Loughran R.M., Possik E.,
RA Vijayaraghavan T., Yang A., Pauli C., Ravi A., Verma A., Yang Z.,
RA Johnson J.L., Wong J.C.Y., Ma Y., Hwang K.S., Weinkove D., Divecha N.,
RA Asara J.M., Elemento O., Rubin M.A., Kimmelman A.C., Pause A.,
RA Cantley L.C., Emerling B.M.;
RT "Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid
RT Metabolism By Facilitating Autophagy.";
RL Mol. Cell 70:531.e9-544.e9(2018).
CC -!- FUNCTION: Participates in the biosynthesis of phosphatidylinositol 4,5-
CC bisphosphate. Preferentially utilizes GTP, rather than ATP, for PI(5)P
CC phosphorylation and its activity reflects changes in direct proportion
CC to the physiological GTP concentration. Its GTP-sensing activity is
CC critical for metabolic adaptation. In collaboration with PIP4K2A, has a
CC role in mediating autophagy in times of nutrient stress
CC (PubMed:29727621). Required for autophagosome-lysosome fusion and the
CC regulation of cellular lipid metabolism (PubMed:29727621). PIP4Ks
CC negatively regulate insulin signaling through a catalytic-independent
CC mechanism. They interact with PIP5Ks and suppress PIP5K-mediated
CC PtdIns(4,5)P2 synthesis and insulin-dependent conversion to
CC PtdIns(3,4,5)P3 (By similarity). {ECO:0000250|UniProtKB:P78356,
CC ECO:0000269|PubMed:29727621}.
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:0000250|UniProtKB:P78356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281;
CC Evidence={ECO:0000250|UniProtKB:P78356};
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:0000250|UniProtKB:P78356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993;
CC Evidence={ECO:0000250|UniProtKB:P78356};
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:0000250|UniProtKB:P78356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965;
CC Evidence={ECO:0000250|UniProtKB:P78356};
CC -!- SUBUNIT: Homodimer. Binds TNFRSF1A. Interacts with PIP4K2A; the
CC interaction suppresses ubiquitination by the SPOP/CUL3 complex (By
CC similarity). Probably interacts with PIP5K1A; the interaction inhibits
CC PIP5K1A kinase activity (By similarity). {ECO:0000250|UniProtKB:P78356,
CC ECO:0000250|UniProtKB:Q8TBX8}.
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 {ECO:0000250}.
CC Cytoplasm {ECO:0000250}. Note=Associated with the plasma membrane and
CC the endoplasmic reticulum. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is
CC stimulated by PtdIns5P levels. {ECO:0000250|UniProtKB:P78356}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250|UniProtKB:P78356}.
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DR EMBL; BC047282; AAH47282.1; -; mRNA.
DR EMBL; AY050219; AAL18245.1; -; mRNA.
DR CCDS; CCDS25329.1; -.
DR RefSeq; NP_473392.1; NM_054051.1.
DR AlphaFoldDB; Q80XI4; -.
DR SMR; Q80XI4; -.
DR BioGRID; 223820; 14.
DR IntAct; Q80XI4; 1.
DR STRING; 10090.ENSMUSP00000018691; -.
DR iPTMnet; Q80XI4; -.
DR PhosphoSitePlus; Q80XI4; -.
DR EPD; Q80XI4; -.
DR MaxQB; Q80XI4; -.
DR PaxDb; Q80XI4; -.
DR PRIDE; Q80XI4; -.
DR ProteomicsDB; 289564; -.
DR Antibodypedia; 72369; 188 antibodies from 25 providers.
DR DNASU; 108083; -.
DR Ensembl; ENSMUST00000018691; ENSMUSP00000018691; ENSMUSG00000018547.
DR GeneID; 108083; -.
DR KEGG; mmu:108083; -.
DR UCSC; uc007leq.1; mouse.
DR CTD; 8396; -.
DR MGI; MGI:1934234; Pip4k2b.
DR VEuPathDB; HostDB:ENSMUSG00000018547; -.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000159874; -.
DR HOGENOM; CLU_004312_7_0_1; -.
DR InParanoid; Q80XI4; -.
DR OMA; MKSHENA; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; Q80XI4; -.
DR TreeFam; TF354315; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8847453; Synthesis of PIPs in the nucleus.
DR BioGRID-ORCS; 108083; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Pip4k2b; mouse.
DR PRO; PR:Q80XI4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80XI4; protein.
DR Bgee; ENSMUSG00000018547; Expressed in cortical plate and 254 other tissues.
DR ExpressionAtlas; Q80XI4; baseline and differential.
DR Genevisible; Q80XI4; MM.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:1902635; P:1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:0090217; P:negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
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 Acetylation; ATP-binding; Cell membrane; Cytoplasm;
KW Direct protein sequencing; 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:0000250|UniProtKB:P78356"
FT CHAIN 2..416
FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2
FT beta"
FT /id="PRO_0000185471"
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:0000250|UniProtKB:P78356"
FT BINDING 203..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 214
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 369
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P78356"
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:0000250|UniProtKB:P78356"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 416 AA; 47319 MW; F967720CF3979550 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
RAEEEECEND GVGGSLLCSY GTPPDSPGNL LSFPRFFGPG EFDPSVDVYA MKSHESAPKK
EVYFMAIIDI LTPYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFNEF MSNILT
