PI42A_MOUSE
ID PI42A_MOUSE Reviewed; 405 AA.
AC O70172;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha {ECO:0000305};
DE EC=2.7.1.149 {ECO:0000250|UniProtKB:P48426};
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha;
DE AltName: Full=Diphosphoinositide kinase 2-alpha;
DE AltName: Full=Phosphatidylinositol 5-Phosphate 4-Kinase;
DE Short=PI5P4Kalpha;
DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II alpha;
DE Short=PI(5)P 4-kinase type II alpha;
DE Short=PIP4KII-alpha;
DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-alpha;
GN Name=Pip4k2a {ECO:0000312|MGI:MGI:1298206}; Synonyms=Pi5p4ka, Pip5k2a;
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 [MRNA].
RX PubMed=9535851; DOI=10.1074/jbc.273.15.8741;
RA Ishihara H., Shibasaki Y., Kizuki N., Wada T., Yazaki Y., Asano T., Oka Y.;
RT "Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third
RT isoform and deletion/substitution analysis of members of this novel lipid
RT kinase family.";
RL J. Biol. Chem. 273:8741-8748(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [3]
RP PROTEIN SEQUENCE OF 262-270, 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 FUNCTION IN THROMBOPOIESIS, AND SUBCELLULAR LOCATION.
RX PubMed=16434494; DOI=10.1182/blood-2005-07-2755;
RA Schulze H., Korpal M., Hurov J., Kim S.-W., Zhang J., Cantley L.C.,
RA Graf T., Shivdasani R.A.;
RT "Characterization of the megakaryocyte demarcation membrane system and its
RT role in thrombopoiesis.";
RL Blood 107:3868-3875(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, 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 [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20204506; DOI=10.1007/s11064-010-0146-y;
RA Huang Z., Anderson R.E., Cao W., Wiechmann A.F., Rajala R.V.S.;
RT "Light-induced tyrosine phosphorylation of rod outer segment membrane
RT proteins regulate the translocation, membrane binding and activation of
RT type II alpha phosphatidylinositol-5-phosphate 4-kinase.";
RL Neurochem. Res. 36:627-635(2011).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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: Catalyzes the phosphorylation of phosphatidylinositol 5-
CC phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring,
CC to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Has both
CC ATP- and GTP-dependent kinase activities. May exert its function by
CC regulating the levels of PtdIns5P, which functions in the cytosol by
CC increasing AKT activity and in the nucleus signals through ING2 (By
CC similarity). May regulate the pool of cytosolic PtdIns5P in response to
CC the activation of tyrosine phosphorylation (By similarity). Required
CC for lysosome-peroxisome membrane contacts and intracellular cholesterol
CC transport through modulating peroxisomal PtdIns(4,5)P2 level (By
CC similarity). In collaboration with PIP4K2B, has a role in mediating
CC autophagy in times of nutrient stress (PubMed:29727621). Required for
CC autophagosome-lysosome fusion and the regulation of cellular lipid
CC metabolism (PubMed:29727621). Negatively regulates insulin signaling
CC through a catalytic-independent mechanism. PIP4Ks interact with PIP5Ks
CC and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-
CC dependent conversion to PtdIns(3,4,5)P3 (By similarity). May be
CC involved in thrombopoiesis, and the terminal maturation of
CC megakaryocytes and regulation of their size (PubMed:16434494).
CC {ECO:0000250|UniProtKB:P48426, ECO:0000250|UniProtKB:Q9R0I8,
CC ECO:0000269|PubMed:16434494, 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:P48426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281;
CC Evidence={ECO:0000250|UniProtKB:P48426};
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:P48426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993;
CC Evidence={ECO:0000250|UniProtKB:P48426};
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:P48426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965;
CC Evidence={ECO:0000250|UniProtKB:P48426};
CC -!- ACTIVITY REGULATION: In rod outer segments, activated by light.
CC {ECO:0000250|UniProtKB:Q9R0I8}.
CC -!- SUBUNIT: Homodimer. Interacts with PIP4K2B; the interaction may
CC regulate localization to the nucleus (By similarity). Probably
CC interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase
CC activity (By similarity). {ECO:0000250|UniProtKB:P48426,
CC ECO:0000250|UniProtKB:Q8TBX8}.
CC -!- INTERACTION:
CC O70172; Q96A65: EXOC4; Xeno; NbExp=3; IntAct=EBI-644828, EBI-355383;
CC O70172; Q13496: MTM1; Xeno; NbExp=2; IntAct=EBI-644828, EBI-2864109;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20204506}.
CC Nucleus {ECO:0000250|UniProtKB:P48426}. Lysosome
CC {ECO:0000269|PubMed:29727621}. Cytoplasm {ECO:0000269|PubMed:20204506}.
CC Photoreceptor inner segment {ECO:0000305|PubMed:20204506}. Cell
CC projection, cilium, photoreceptor outer segment
CC {ECO:0000305|PubMed:20204506}. Note=May translocate from the cytosol to
CC the cell membrane upon activation of tyrosine phosphorylation. May
CC translocate from the inner to the outer segments of the rod
CC photoreceptor cells in response to light (PubMed:20204506).
CC Localization to the nucleus is modulated by the interaction with
CC PIP4K2B (By similarity). {ECO:0000250|UniProtKB:P48426,
CC ECO:0000269|PubMed:20204506}.
CC -!- TISSUE SPECIFICITY: Detected in rod photoreceptor cells.
CC {ECO:0000269|PubMed:20204506}.
CC -!- PTM: Phosphorylated in tyrosines. Phosphorylation is induced by light
CC and increases kinase activity. {ECO:0000250|UniProtKB:Q9R0I8}.
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DR EMBL; AB009615; BAA25676.1; -; mRNA.
DR EMBL; BC011097; AAH11097.1; -; mRNA.
DR CCDS; CCDS15712.1; -.
DR RefSeq; NP_032871.3; NM_008845.4.
DR AlphaFoldDB; O70172; -.
DR SMR; O70172; -.
DR BioGRID; 202170; 12.
DR DIP; DIP-49438N; -.
DR IntAct; O70172; 7.
DR MINT; O70172; -.
DR STRING; 10090.ENSMUSP00000006912; -.
DR iPTMnet; O70172; -.
DR PhosphoSitePlus; O70172; -.
DR SwissPalm; O70172; -.
DR EPD; O70172; -.
DR PaxDb; O70172; -.
DR PeptideAtlas; O70172; -.
DR PRIDE; O70172; -.
DR ProteomicsDB; 289563; -.
DR Antibodypedia; 25686; 367 antibodies from 33 providers.
DR DNASU; 18718; -.
DR Ensembl; ENSMUST00000006912; ENSMUSP00000006912; ENSMUSG00000026737.
DR GeneID; 18718; -.
DR KEGG; mmu:18718; -.
DR UCSC; uc008imb.1; mouse.
DR CTD; 5305; -.
DR MGI; MGI:1298206; Pip4k2a.
DR VEuPathDB; HostDB:ENSMUSG00000026737; -.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000156508; -.
DR HOGENOM; CLU_004312_7_0_1; -.
DR InParanoid; O70172; -.
DR OMA; LTRMHLM; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; O70172; -.
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; 18718; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Pip4k2a; mouse.
DR PRO; PR:O70172; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O70172; protein.
DR Bgee; ENSMUSG00000026737; Expressed in cerebellar nuclear complex and 275 other tissues.
DR ExpressionAtlas; O70172; baseline and differential.
DR Genevisible; O70172; MM.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell.
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; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
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:0035855; P:megakaryocyte development; 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: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 GO; GO:0090119; P:vesicle-mediated cholesterol transport; ISS: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; Cell projection; Cytoplasm;
KW Direct protein sequencing; Kinase; Lipid metabolism; Lysosome; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT CHAIN 2..405
FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2
FT alpha"
FT /id="PRO_0000185466"
FT DOMAIN 33..405
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 59..65
FT /note="Required for interaction with PIP5K1A"
FT /evidence="ECO:0000250|UniProtKB:Q8TBX8"
FT REGION 288..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..302
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 309..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 145
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
SQ SEQUENCE 405 AA; 46152 MW; 2D6CC431BDA4D967 CRC64;
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM
LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA
PLPNDSQARS GARFHTSYDK RYVIKTITSE DVAEMHNILK KYHQYIVECH GVTLLPQFLG
MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN
EGQKIYIDDN NKKIFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE
EGESDSTHPI GTPPDSPGNT LNSSPPLAPG EFDPNIDVYA IKCHENAPRK EVYFMAIIDI
LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF IGHIL
