P4K2A_RAT
ID P4K2A_RAT Reviewed; 478 AA.
AC Q99M64;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67 {ECO:0000269|PubMed:11244087};
DE AltName: Full=55 kDa type II phosphatidylinositol 4-kinase;
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=Pi4k2a; Synonyms=Pi4kii;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND PALMITOYLATION.
RC TISSUE=Brain;
RX PubMed=11244087; DOI=10.1074/jbc.c000861200;
RA Barylko B., Gerber S.H., Binns D.D., Grichine N., Khvotchev M.,
RA Suedhof T.C., Albanesi J.P.;
RT "A novel family of phosphatidylinositol 4-kinases conserved from yeast to
RT humans.";
RL J. Biol. Chem. 276:7705-7708(2001).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-50, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3]
RP 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 [4]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-60 AND LEU-61, SUBUNIT, AND
RP INTERACTION WITH BLOC1S5 AND DTNBP1.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-9; SER-46 AND SER-461,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(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:11244087, 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:11244087};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=88 uM for ATP;
CC KM=45 uM for PtdIns;
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 Interacts with BLOC1S5 and DTNBP1 (PubMed:21998198). Interacts with
CC FOS; this interaction may enhance phosphatidylinositol phosphorylation
CC activity (By similarity). Interacts with ITCH (By similarity).
CC Interacts with ATG9A (By similarity). {ECO:0000250|UniProtKB:Q2TBE6,
CC ECO:0000269|PubMed:21998198}.
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 {ECO:0000269|PubMed:21998198}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:21998198}. Cell projection,
CC dendrite {ECO:0000250|UniProtKB:Q2TBE6}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q2TBE6}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q2TBE6}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q2TBE6}. Membrane {ECO:0000269|PubMed:11244087};
CC Lipid-anchor {ECO:0000269|PubMed:11244087}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9BTU6}. Perikaryon
CC {ECO:0000250|UniProtKB:Q2TBE6}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q2TBE6}. 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. {ECO:0000250|UniProtKB:Q2TBE6}.
CC -!- TISSUE SPECIFICITY: Detected in adult brain, especially in neurons in
CC the cerebellum, brain cortex, dorsal root ganglion and spinal cord (at
CC protein level). {ECO:0000269|PubMed:19581584}.
CC -!- PTM: Ubiquitinated by ITCH; this does not lead to proteasomal
CC degradation. {ECO:0000250|UniProtKB:Q9BTU6}.
CC -!- PTM: Palmitoylated (PubMed:11244087). Palmitoylated by ZDHHC3 and
CC ZDHHC7 in the CCPCC motif. Palmitoylation is cholesterol-dependent, and
CC required for TGN localization (By similarity).
CC {ECO:0000250|UniProtKB:Q9BTU6, ECO:0000269|PubMed:11244087}.
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; AY029199; AAK33002.1; -; mRNA.
DR RefSeq; NP_446187.1; NM_053735.1.
DR AlphaFoldDB; Q99M64; -.
DR SMR; Q99M64; -.
DR BioGRID; 250373; 1.
DR IntAct; Q99M64; 3.
DR MINT; Q99M64; -.
DR STRING; 10116.ENSRNOP00000019874; -.
DR iPTMnet; Q99M64; -.
DR PhosphoSitePlus; Q99M64; -.
DR SwissPalm; Q99M64; -.
DR jPOST; Q99M64; -.
DR PaxDb; Q99M64; -.
DR PRIDE; Q99M64; -.
DR Ensembl; ENSRNOT00000019874; ENSRNOP00000019874; ENSRNOG00000014675.
DR GeneID; 114554; -.
DR KEGG; rno:114554; -.
DR UCSC; RGD:620485; rat.
DR CTD; 55361; -.
DR RGD; 620485; Pi4k2a.
DR eggNOG; KOG2381; Eukaryota.
DR GeneTree; ENSGT00390000010434; -.
DR HOGENOM; CLU_032516_2_0_1; -.
DR InParanoid; Q99M64; -.
DR OMA; YIIRNTX; -.
DR OrthoDB; 1273723at2759; -.
DR PhylomeDB; Q99M64; -.
DR TreeFam; TF314740; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR PRO; PR:Q99M64; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000014675; Expressed in cerebellum and 19 other tissues.
DR Genevisible; Q99M64; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; IDA:RGD.
DR GO; GO:0000139; C:Golgi membrane; ISO:RGD.
DR GO; GO:0035838; C:growing cell tip; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0031224; C:intrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISS: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; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:RGD.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0002561; P:basophil degranulation; IMP:RGD.
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; ISO:RGD.
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..478
FT /note="Phosphatidylinositol 4-kinase type 2-alpha"
FT /id="PRO_0000285160"
FT DOMAIN 123..452
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..135
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 156..158
FT /note="Important for substrate binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 164..177
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 267..275
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 304..312
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 343..363
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 358..367
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 130..136
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 151
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 260..263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 345
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:0007744|PubMed:22673903"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 173
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 174
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 176
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 MUTAGEN 60
FT /note="L->A: Reduces targeting to synaptic vesicles and
FT neurite tips; when associated with A-61."
FT /evidence="ECO:0000269|PubMed:21998198"
FT MUTAGEN 61
FT /note="L->A: Reduces targeting to synaptic vesicles and
FT neurite tips; when associated with A-60."
FT /evidence="ECO:0000269|PubMed:21998198"
SQ SEQUENCE 478 AA; 54305 MW; EBE4BFFB4574FD1F CRC64;
MDETSPLVSP ERAQPPEYTF PSVSGAHFPQ VPGGAVRVAA AGSGPSPPCS PGHDRERQPL
LDRARGAAAQ GQTHTVAAQA QALAAQAAVA VHAVQTHRER NDFPEDPEFE VVVRQAEIAI
ECSIYPERIY QGSSGSYFVK DSQGRIIAVF KPKNEEPYGN LNPKWTKWLQ KLCCPCCFGR
DCLVLNQGYL SEAGASLVDQ KLELNIVPRT KVVYLASETF NYSAIDRVKS RGKRLALEKV
PKVGQRFNRI GLPPKVGSFQ LFVEGYKDAD YWLRRFEAEP LPENTNRQLL LQFERLVVLD
YIIRNTDRGN DNWLIKYDYP MDNPNCRDTD WVMVREPVIK VAAIDNGLAF PLKHPDSWRA
YPFYWAWLPQ AKVPFSQEIK DLILPKISDP NFVKDLEEDL YELFKKDPGF DRGQFHKQIA
VMRGQILNLT QALKDNKSPL HLVQMPPVIV ETARSHQRSS SESYTQSFQS RKPFFSWW
