P4K2A_MOUSE
ID P4K2A_MOUSE Reviewed; 479 AA.
AC Q2TBE6;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67 {ECO:0000269|PubMed:19581584};
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=Pi4k2a;
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 STRAIN=FVB/N; 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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [4]
RP DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=19581584; DOI=10.1073/pnas.0903011106;
RA Simons J.P., Al-Shawi R., Minogue S., Waugh M.G., Wiedemann C.,
RA Evangelou S., Loesch A., Sihra T.S., King R., Warner T.T., Hsuan J.J.;
RT "Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset
RT degeneration of spinal cord axons.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11535-11539(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 SUBUNIT.
RX PubMed=21998198; DOI=10.1091/mbc.e11-07-0592;
RA Larimore J., Tornieri K., Ryder P.V., Gokhale A., Zlatic S.A., Craige B.,
RA Lee J.D., Talbot K., Pare J.F., Smith Y., Faundez V.;
RT "The schizophrenia susceptibility factor dysbindin and its associated
RT complex sort cargoes from cell bodies to the synapse.";
RL Mol. Biol. Cell 22:4854-4867(2011).
RN [7]
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND INTERACTION WITH ITCH.
RX PubMed=23146885; DOI=10.1038/embor.2012.164;
RA Mossinger J., Wieffer M., Krause E., Freund C., Gerth F., Krauss M.,
RA Haucke V.;
RT "Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated
RT by the ubiquitin ligase Itch.";
RL EMBO Rep. 13:1087-1094(2012).
RN [8]
RP INTERACTION WITH FOS.
RX PubMed=22105363; DOI=10.1038/onc.2011.510;
RA Ferrero G.O., Velazquez F.N., Caputto B.L.;
RT "The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos
RT tyrosine phosphorylation and c-Fos phospholipid synthesis activation
RT capacity.";
RL Oncogene 31:3381-3391(2012).
CC -!- FUNCTION: Membrane-bound phosphatidylinositol-4 kinase (PI4-kinase)
CC that catalyzes the phosphorylation of phosphatidylinositol (PI) to
CC phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important
CC roles in endocytosis, Golgi function, protein sorting and membrane
CC trafficking and is required for prolonged survival of neurons. Besides,
CC phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-
CC phosphate (PI4P) is the first committed step in the generation of
CC phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second
CC messenger inositol 1,4,5-trisphosphate (InsP3).
CC {ECO:0000269|PubMed:19581584, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:19877, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58178, ChEBI:CHEBI:456216;
CC EC=2.7.1.67; Evidence={ECO:0000269|PubMed:19581584};
CC -!- SUBUNIT: Associates with the BLOC-1 and the AP-3 complexes; the BLOC-1
CC complex is required for optimal binding of PI4K2A to the AP-3 complex
CC (PubMed:21998198). Interacts with BLOC1S5 and DTNBP1 (By similarity).
CC Interacts with ITCH (PubMed:23146885). Interacts with FOS; this
CC interaction may enhance phosphatidylinositol phosphorylation activity
CC (PubMed:22105363). Interacts with ATG9A (By similarity).
CC {ECO:0000250|UniProtKB:Q9BTU6, ECO:0000269|PubMed:21998198,
CC ECO:0000269|PubMed:22105363, ECO:0000269|PubMed:23146885}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q9BTU6}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q9BTU6}. Membrane raft
CC {ECO:0000250|UniProtKB:Q9BTU6}. Endosome
CC {ECO:0000250|UniProtKB:Q99M64}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q99M64}. Cell projection, dendrite
CC {ECO:0000269|PubMed:21998198}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:21998198}. Synapse, synaptosome
CC {ECO:0000269|PubMed:21998198}. Mitochondrion
CC {ECO:0000269|PubMed:21998198}. Membrane {ECO:0000269|PubMed:19581584};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q9BTU6}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9BTU6}. Perikaryon
CC {ECO:0000269|PubMed:21998198}. Cell projection, neuron projection
CC {ECO:0000269|PubMed:21998198}. Note=Found in subdomains of the plasma
CC membrane termed non-caveolar membrane rafts. Transported from neuronal
CC cell body to neuron projections and neurite tips in a BLOC-1- and AP-3-
CC complexes-dependent manner (PubMed:21998198).
CC {ECO:0000269|PubMed:21998198}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level).
CC {ECO:0000269|PubMed:19581584}.
CC -!- PTM: Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif.
CC Palmitoylation is cholesterol-dependent, and required for TGN
CC localization (By similarity). {ECO:0000250|UniProtKB:Q9BTU6}.
CC -!- PTM: Ubiquitinated by ITCH; this does not lead to proteasomal
CC degradation. {ECO:0000269|PubMed:23146885}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate.
CC Young animals have no visible phenotype, but oldeer mice develop
CC urinary incontinence, head tremor, spastic gait, weakness of the hind
CC limbs, followed by additional weakness of the forelimbs, weight loss
CC and premature death. Their brains show no gross anatomical defects, but
CC show loss of Purkinje cells. In addition, mice present massive axon
CC degeneration in the ascending and descending tract of the spinal cord.
CC Male mice are infertile and females are subfertile.
CC {ECO:0000269|PubMed:19581584}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC110363; AAI10364.1; -; mRNA.
DR CCDS; CCDS29821.1; -.
DR RefSeq; NP_663476.1; NM_145501.2.
DR RefSeq; XP_011245707.1; XM_011247405.2.
DR AlphaFoldDB; Q2TBE6; -.
DR SMR; Q2TBE6; -.
DR BioGRID; 220002; 24.
DR IntAct; Q2TBE6; 4.
DR MINT; Q2TBE6; -.
DR STRING; 10090.ENSMUSP00000069284; -.
DR iPTMnet; Q2TBE6; -.
DR PhosphoSitePlus; Q2TBE6; -.
DR SwissPalm; Q2TBE6; -.
DR EPD; Q2TBE6; -.
DR jPOST; Q2TBE6; -.
DR MaxQB; Q2TBE6; -.
DR PaxDb; Q2TBE6; -.
DR PeptideAtlas; Q2TBE6; -.
DR PRIDE; Q2TBE6; -.
DR ProteomicsDB; 294365; -.
DR DNASU; 84095; -.
DR Ensembl; ENSMUST00000066778; ENSMUSP00000069284; ENSMUSG00000025178.
DR Ensembl; ENSMUST00000235932; ENSMUSP00000158574; ENSMUSG00000025178.
DR GeneID; 84095; -.
DR KEGG; mmu:84095; -.
DR UCSC; uc008hnf.1; mouse.
DR CTD; 55361; -.
DR MGI; MGI:1934031; Pi4k2a.
DR VEuPathDB; HostDB:ENSMUSG00000025178; -.
DR eggNOG; KOG2381; Eukaryota.
DR GeneTree; ENSGT00390000010434; -.
DR HOGENOM; CLU_032516_2_0_1; -.
DR InParanoid; Q2TBE6; -.
DR OMA; YIIRNTX; -.
DR OrthoDB; 1273723at2759; -.
DR PhylomeDB; Q2TBE6; -.
DR TreeFam; TF314740; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR BioGRID-ORCS; 84095; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Pi4k2a; mouse.
DR PRO; PR:Q2TBE6; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q2TBE6; protein.
DR Bgee; ENSMUSG00000025178; Expressed in pontine nuclear group and 252 other tissues.
DR ExpressionAtlas; Q2TBE6; baseline and differential.
DR Genevisible; Q2TBE6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031083; C:BLOC-1 complex; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0035838; C:growing cell tip; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031224; C:intrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; ISS:UniProtKB.
DR GO; GO:0035651; F:AP-3 adaptor complex binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0002561; P:basophil degranulation; ISO:MGI.
DR GO; GO:0007032; P:endosome organization; IBA:GO_Central.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR InterPro; IPR039756; Lsb6/PI4K2.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR PANTHER; PTHR12865; PTHR12865; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasmic vesicle; Endosome; Golgi apparatus; Kinase; Lipid metabolism;
KW Lipoprotein; Membrane; Mitochondrion; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Synapse; Synaptosome; Transferase;
KW Ubl conjugation.
FT CHAIN 1..479
FT /note="Phosphatidylinositol 4-kinase type 2-alpha"
FT /id="PRO_0000285159"
FT DOMAIN 124..453
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..136
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 157..159
FT /note="Important for substrate binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 165..178
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 268..276
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 305..313
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 344..364
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 359..368
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 131..137
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 261..264
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99M64"
FT LIPID 174
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 175
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 178
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
SQ SEQUENCE 479 AA; 54258 MW; 1D7429AA7BF2918B CRC64;
MDETSPLVSP ERAQPPEYTF PSGSGAHFPQ VPGGAVRVAA AAGSGPSPPC SPGHDRERQP
LLDRARGAAA QGQTHTVAVQ AQALAAQAAV AAHAVQTHRE RNDFPEDPEF EVVVRQAEVA
IECSIYPERI YQGSSGSYFV KDSQGRIVAV FKPKNEEPYG HLNPKWTKWL QKLCCPCCFG
RDCLVLNQGY LSEAGASLVD QKLELNIVPR TKVVYLASET FNYSAIDRVK SRGKRLALEK
VPKVGQRFNR IGLPPKVGSF QLFVEGYKDA DYWLRRFEAE PLPENTNRQL LLQFERLVVL
DYIIRNTDRG NDNWLIKYDC PMDNSSCRDT DWVMVREPVI KVAAIDNGLA FPLKHPDSWR
AYPFYWAWLP QAKVPFSQEI KDLILPKISD PNFIKDLEED LYELFKRDPG FDRGQFHKQI
AVMRGQILNL TQALKDNKSP LHLVQMPPVI VETARSHQRS ASESYTQSFQ SRKPFFSWW
