P4K2A_HUMAN
ID P4K2A_HUMAN Reviewed; 479 AA.
AC Q9BTU6; D3DR59; Q9NSG8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67 {ECO:0000269|PubMed:11279162, ECO:0000269|PubMed:12324459, ECO:0000269|PubMed:20388919, ECO:0000269|PubMed:24675427, ECO:0000269|PubMed:25168678};
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=PI4K2A;
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], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11279162; DOI=10.1074/jbc.m100982200;
RA Minogue S., Anderson J.S., Waugh M.G., dos Santos M., Corless S.,
RA Cramer R., Hsuan J.J.;
RT "Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel
RT lipid kinase family.";
RL J. Biol. Chem. 276:16635-16640(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 222-479.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RC TISSUE=Brain;
RX PubMed=12324459; DOI=10.1074/jbc.m206860200;
RA Wei Y.J., Sun H.Q., Yamamoto M., Wlodarski P., Kunii K., Martinez M.,
RA Barylko B., Albanesi J.P., Yin H.L.;
RT "Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral
RT membrane protein that is recruited to the plasma membrane and activated by
RT Rac-GTP.";
RL J. Biol. Chem. 277:46586-46593(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16443754; DOI=10.1242/jcs.02752;
RA Minogue S., Waugh M.G., De Matteis M.A., Stephens D.J., Berditchevski F.,
RA Hsuan J.J.;
RT "Phosphatidylinositol 4-kinase is required for endosomal trafficking and
RT degradation of the EGF receptor.";
RL J. Cell Sci. 119:571-581(2006).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=20388919; DOI=10.1194/jlr.m005751;
RA Minogue S., Chu K.M., Westover E.J., Covey D.F., Hsuan J.J., Waugh M.G.;
RT "Relationship between phosphatidylinositol 4-phosphate synthesis, membrane
RT organization, and lateral diffusion of PI4KIIalpha at the trans-Golgi
RT network.";
RL J. Lipid Res. 51:2314-2324(2010).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-5; SER-9 AND SER-47, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP SUBCELLULAR LOCATION, INTERACTION WITH ITCH, UBIQUITINATION, AND FUNCTION.
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 [18]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-174; CYS-175; CYS-177 AND
RP CYS-178, AND MUTAGENESIS OF 174-CYS--CYS-178.
RX PubMed=22535966; DOI=10.1074/jbc.m112.348094;
RA Lu D., Sun H.Q., Wang H., Barylko B., Fukata Y., Fukata M., Albanesi J.P.,
RA Yin H.L.;
RT "Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-localized
RT palmitoyltransferases in cholesterol-dependent manner.";
RL J. Biol. Chem. 287:21856-21865(2012).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-9; SER-47 AND SER-51,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-47 AND SER-51, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP INTERACTION WITH ATG9A.
RX PubMed=30917996; DOI=10.1083/jcb.201901115;
RA Judith D., Jefferies H.B.J., Boeing S., Frith D., Snijders A.P.,
RA Tooze S.A.;
RT "ATG9A shapes the forming autophagosome through Arfaptin 2 and
RT phosphatidylinositol 4-kinase IIIbeta.";
RL J. Cell Biol. 218:1634-1652(2019).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 76-172 AND 180-468 IN COMPLEX
RP WITH ATP, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-152;
RP ASN-163; 165-LYS--LYS-172; ARG-275; ASP-308 AND GLN-445.
RX PubMed=25168678; DOI=10.15252/embr.201438841;
RA Baumlova A., Chalupska D., Rozycki B., Jovic M., Wisniewski E., Klima M.,
RA Dubankova A., Kloer D.P., Nencka R., Balla T., Boura E.;
RT "The crystal structure of the phosphatidylinositol 4-kinase IIalpha.";
RL EMBO Rep. 15:1085-1092(2014).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 78-453 IN COMPLEX WITH ADP,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ARG-129; LYS-152; 157-GLU--TYR-159; LYS-165; TRP-166; LYS-168; LYS-172;
RP 174-CYS--CYS-178; LEU-184; PHE-263; ASP-269; ARG-275; ARG-276; ILE-345;
RP LEU-349; TRP-359; TYR-365 AND TRP-368.
RX PubMed=24675427; DOI=10.1038/ncomms4552;
RA Zhou Q., Li J., Yu H., Zhai Y., Gao Z., Liu Y., Pang X., Zhang L.,
RA Schulten K., Sun F., Chen C.;
RT "Molecular insights into the membrane-associated phosphatidylinositol 4-
RT kinase IIalpha.";
RL Nat. Commun. 5:3552-3552(2014).
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:11279162, ECO:0000269|PubMed:16443754,
CC ECO:0000269|PubMed:20388919, ECO:0000269|PubMed:23146885,
CC ECO:0000269|PubMed:24675427, ECO:0000269|PubMed:25168678, 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:11279162,
CC ECO:0000269|PubMed:12324459, ECO:0000269|PubMed:20388919,
CC ECO:0000269|PubMed:24675427, ECO:0000269|PubMed:25168678};
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 (PubMed:23146885).
CC Interacts with ATG9A (PubMed:30917996). {ECO:0000250|UniProtKB:Q2TBE6,
CC ECO:0000269|PubMed:21998198, ECO:0000269|PubMed:23146885,
CC ECO:0000269|PubMed:30917996}.
CC -!- INTERACTION:
CC Q9BTU6; Q96J02: ITCH; NbExp=5; IntAct=EBI-3239392, EBI-1564678;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:12324459, ECO:0000269|PubMed:16443754,
CC ECO:0000269|PubMed:22535966}; Lipid-anchor
CC {ECO:0000269|PubMed:22535966}. Membrane raft
CC {ECO:0000269|PubMed:11279162}. Cell projection, dendrite
CC {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}. Endosome {ECO:0000269|PubMed:16443754,
CC ECO:0000269|PubMed:23146885}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:16443754}. Membrane {ECO:0000269|PubMed:24675427};
CC Lipid-anchor {ECO:0000269|PubMed:24675427}. Cell membrane
CC {ECO:0000269|PubMed:11279162, ECO:0000269|PubMed:16443754}. 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: Widely expressed. Highest expression is observed in
CC kidney, brain, heart, skeletal muscle, and placenta and lowest
CC expression is observed in colon, thymus, and small intestine.
CC {ECO:0000269|PubMed:11279162}.
CC -!- PTM: Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif.
CC Palmitoylation is cholesterol-dependent, and required for TGN
CC localization. {ECO:0000269|PubMed:22535966}.
CC -!- PTM: Ubiquitinated by ITCH; this does not lead to proteasomal
CC degradation. {ECO:0000269|PubMed:23146885}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ303098; CAC38065.1; -; mRNA.
DR EMBL; BT007330; AAP35994.1; -; mRNA.
DR EMBL; AL355315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49906.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49907.1; -; Genomic_DNA.
DR EMBL; BC003167; AAH03167.1; -; mRNA.
DR EMBL; AL353952; CAB89254.1; -; mRNA.
DR CCDS; CCDS7469.1; -.
DR PIR; T48687; T48687.
DR RefSeq; NP_060895.1; NM_018425.3.
DR PDB; 4HND; X-ray; 3.20 A; A/B=78-453.
DR PDB; 4HNE; X-ray; 2.95 A; A/B=78-453.
DR PDB; 4PLA; X-ray; 2.77 A; A=180-468.
DR PDB; 4YC4; X-ray; 2.58 A; A=180-468.
DR PDB; 5EUT; X-ray; 2.80 A; A=179-468.
DR PDB; 5I0N; X-ray; 2.28 A; A=180-468.
DR PDBsum; 4HND; -.
DR PDBsum; 4HNE; -.
DR PDBsum; 4PLA; -.
DR PDBsum; 4YC4; -.
DR PDBsum; 5EUT; -.
DR PDBsum; 5I0N; -.
DR AlphaFoldDB; Q9BTU6; -.
DR SMR; Q9BTU6; -.
DR BioGRID; 120639; 71.
DR CORUM; Q9BTU6; -.
DR IntAct; Q9BTU6; 21.
DR MINT; Q9BTU6; -.
DR STRING; 9606.ENSP00000359665; -.
DR BindingDB; Q9BTU6; -.
DR ChEMBL; CHEMBL2251; -.
DR DrugCentral; Q9BTU6; -.
DR GuidetoPHARMACOLOGY; 2498; -.
DR GlyGen; Q9BTU6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BTU6; -.
DR PhosphoSitePlus; Q9BTU6; -.
DR SwissPalm; Q9BTU6; -.
DR BioMuta; PI4K2A; -.
DR DMDM; 74752344; -.
DR EPD; Q9BTU6; -.
DR jPOST; Q9BTU6; -.
DR MassIVE; Q9BTU6; -.
DR MaxQB; Q9BTU6; -.
DR PaxDb; Q9BTU6; -.
DR PeptideAtlas; Q9BTU6; -.
DR PRIDE; Q9BTU6; -.
DR ProteomicsDB; 79011; -.
DR Antibodypedia; 35004; 187 antibodies from 30 providers.
DR DNASU; 55361; -.
DR Ensembl; ENST00000370631.3; ENSP00000359665.3; ENSG00000155252.13.
DR GeneID; 55361; -.
DR KEGG; hsa:55361; -.
DR MANE-Select; ENST00000370631.4; ENSP00000359665.3; NM_018425.4; NP_060895.1.
DR UCSC; uc001kog.2; human.
DR CTD; 55361; -.
DR DisGeNET; 55361; -.
DR GeneCards; PI4K2A; -.
DR HGNC; HGNC:30031; PI4K2A.
DR HPA; ENSG00000155252; Low tissue specificity.
DR MIM; 609763; gene.
DR neXtProt; NX_Q9BTU6; -.
DR OpenTargets; ENSG00000155252; -.
DR PharmGKB; PA162399304; -.
DR VEuPathDB; HostDB:ENSG00000155252; -.
DR eggNOG; KOG2381; Eukaryota.
DR GeneTree; ENSGT00390000010434; -.
DR HOGENOM; CLU_032516_2_0_1; -.
DR InParanoid; Q9BTU6; -.
DR OMA; ENYAMES; -.
DR OrthoDB; 1273723at2759; -.
DR PhylomeDB; Q9BTU6; -.
DR TreeFam; TF314740; -.
DR BioCyc; MetaCyc:HS00573-MON; -.
DR BRENDA; 2.7.1.67; 2681.
DR PathwayCommons; Q9BTU6; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR SignaLink; Q9BTU6; -.
DR SIGNOR; Q9BTU6; -.
DR BioGRID-ORCS; 55361; 18 hits in 1074 CRISPR screens.
DR ChiTaRS; PI4K2A; human.
DR GeneWiki; PI4K2A; -.
DR GenomeRNAi; 55361; -.
DR Pharos; Q9BTU6; Tbio.
DR PRO; PR:Q9BTU6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9BTU6; protein.
DR Bgee; ENSG00000155252; Expressed in lower esophagus mucosa and 185 other tissues.
DR Genevisible; Q9BTU6; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0035838; C:growing cell tip; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0031224; C:intrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IDA:UniProtKB.
DR GO; GO:0035651; F:AP-3 adaptor complex binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA: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 3D-structure; 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_0000285158"
FT DOMAIN 124..453
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..74
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:0000305|PubMed:24675427"
FT REGION 165..178
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000305|PubMed:24675427,
FT ECO:0000305|PubMed:25168678"
FT REGION 268..276
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000305|PubMed:24675427"
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:0000305|PubMed:24675427"
FT BINDING 131..137
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24675427,
FT ECO:0000269|PubMed:25168678"
FT BINDING 152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24675427,
FT ECO:0000269|PubMed:25168678"
FT BINDING 261..264
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24675427,
FT ECO:0000269|PubMed:25168678"
FT BINDING 346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24675427,
FT ECO:0000269|PubMed:25168678"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99M64"
FT LIPID 174
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:22535966,
FT ECO:0000305|PubMed:24675427"
FT LIPID 175
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:22535966,
FT ECO:0000305|PubMed:24675427"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:22535966,
FT ECO:0000305|PubMed:24675427"
FT LIPID 178
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:22535966,
FT ECO:0000305|PubMed:24675427"
FT MUTAGEN 129
FT /note="R->E: Reduces enzyme activity, probably due to
FT impaired membrane-association; when associated with E-275
FT and E-276."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 152
FT /note="K->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:24675427,
FT ECO:0000269|PubMed:25168678"
FT MUTAGEN 157..159
FT /note="EPY->APA: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 163
FT /note="N->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:25168678"
FT MUTAGEN 165..172
FT /note="KWTKWLQK->AAAAAAAA: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:25168678"
FT MUTAGEN 165
FT /note="K->A: Abolishes enzyme activity; when associated
FT with A-168 and A-172."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 166
FT /note="W->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 168
FT /note="K->A: Abolishes enzyme activity; when associated
FT with A-165 and A-172."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 172
FT /note="K->A: Abolishes enzyme activity; when associated
FT with A-165 and A-168."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 174..178
FT /note="CCPCC->FFPFF: No effect on membrane-association."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 174..178
FT /note="CCPCC->SSPSS: Abolishes palmitoylation and impairs
FT membrane-association."
FT /evidence="ECO:0000269|PubMed:22535966,
FT ECO:0000269|PubMed:24675427"
FT MUTAGEN 184
FT /note="L->A: Abolishes enzyme activity; when associated
FT with A-349."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 263
FT /note="F->A: Abolishes enzyme activity; when associated
FT with A-345."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 269
FT /note="D->A: Reduces enzyme activity by half."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 275
FT /note="R->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:25168678"
FT MUTAGEN 275
FT /note="R->E: Reduces enzyme activity, probably due to
FT impaired membrane-association; when associated with E-129
FT and E-276."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 276
FT /note="R->E: Reduces enzyme activity, probably due to
FT impaired membrane-association; when associated with E-129
FT and E-275."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 308
FT /note="D->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:25168678"
FT MUTAGEN 345
FT /note="I->A: Abolishes enzyme activity; when associated
FT with A-263."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 349
FT /note="L->A: Abolishes enzyme activity; when associated
FT with A-184."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 359
FT /note="W->A: Strongly reduced enzyme activity, probably due
FT to impaired membrane-association. Abolishes enzyme
FT activity; when associated with A-365 and A-368."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 365
FT /note="Y->A: Reduces enzyme activity, probably due to
FT impaired membrane-association. Abolishes enzyme activity;
FT when associated with A-368 and A-359."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 368
FT /note="W->A: Reduces enzyme activity, probably due to
FT impaired membrane-association. Abolishes enzyme activity;
FT when associated with A-359 and A-365."
FT /evidence="ECO:0000269|PubMed:24675427"
FT MUTAGEN 445
FT /note="Q->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:25168678"
FT HELIX 78..93
FT /evidence="ECO:0007829|PDB:4HNE"
FT HELIX 95..99
FT /evidence="ECO:0007829|PDB:4HNE"
FT HELIX 108..122
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:4YC4"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:5I0N"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 167..171
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 189..203
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:4HNE"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:4HNE"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:4PLA"
FT HELIX 270..279
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 284..304
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:5I0N"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:5I0N"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 370..373
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 378..388
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 391..405
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 413..435
FT /evidence="ECO:0007829|PDB:5I0N"
FT HELIX 440..444
FT /evidence="ECO:0007829|PDB:5I0N"
SQ SEQUENCE 479 AA; 54022 MW; 9C9F4CE23F197BBD CRC64;
MDETSPLVSP ERAQPPDYTF PSGSGAHFPQ VPGGAVRVAA AAGSGPSPPG SPGHDRERQP
LLDRARGAAA QGQTQTVAAQ AQALAAQAAA AAHAAQAHRE RNEFPEDPEF EAVVRQAELA
IERCIFPERI YQGSSGSYFV KDPQGRIIAV FKPKNEEPYG HLNPKWTKWL QKLCCPCCFG
RDCLVLNQGY LSEAGASLVD QKLELNIVPR TKVVYLASET FNYSAIDRVK SRGKRLALEK
VPKVGQRFNR IGLPPKVGSF QLFVEGYKDA DYWLRRFEAE PLPENTNRQL LLQFERLVVL
DYIIRNTDRG NDNWLIKYDC PMDSSSSRDT DWVVVKEPVI KVAAIDNGLA FPLKHPDSWR
AYPFYWAWLP QAKVPFSQEI KDLILPKISD PNFVKDLEED LYELFKKDPG FDRGQFHKQI
AVMRGQILNL TQALKDNKSP LHLVQMPPVI VETARSHQRS SSESYTQSFQ SRKPFFSWW
