Full text data of PI4K2A
PI4K2A
[Confidence: high (present in two of the MS resources)]
Phosphatidylinositol 4-kinase type 2-alpha; 2.7.1.67 (Phosphatidylinositol 4-kinase type II-alpha)
Phosphatidylinositol 4-kinase type 2-alpha; 2.7.1.67 (Phosphatidylinositol 4-kinase type II-alpha)
hRBCD
IPI00020124
IPI00020124 Phosphatidylinositol 4-kinase type II Phosphatidylinositol 4-kinase type II membrane n/a n/a n/a n/a 1 n/a 1 n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a integral to membrane n/a found at its expected molecular weight found at molecular weight
IPI00020124 Phosphatidylinositol 4-kinase type II Phosphatidylinositol 4-kinase type II membrane n/a n/a n/a n/a 1 n/a 1 n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a integral to membrane n/a found at its expected molecular weight found at molecular weight
UniProt
Q9BTU6
ID P4K2A_HUMAN Reviewed; 479 AA.
AC Q9BTU6; D3DR59; Q9NSG8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67;
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=PI4K2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
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
RT novel 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
RT 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-462, AND MASS
RP SPECTROMETRY.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-51; SER-462 AND
RP SER-464, AND MASS SPECTROMETRY.
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-5; SER-9 AND SER-47, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
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.,
RA Craige B., 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
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.,
RA Albanesi J.P., Yin H.L.;
RT "Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-
RT localized palmitoyltransferases in cholesterol-dependent manner.";
RL J. Biol. Chem. 287:21856-21865(2012).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Together with PI4K2B and the type III PI4Ks (PIK4CA and
CC PIK4CB) it contributes to the overall PI4-kinase activity of the
CC cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is
CC the first committed step in the generation of phosphatidylinositol
CC 4,5-bisphosphate (PIP2), a precursor of the second messenger
CC inositol 1,4,5-trisphosphate (InsP3). Contributes to the
CC production of InsP3 in stimulated cells (By similarity). This
CC lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P)
CC producer in the Golgi apparatus, it generates more than 50% of
CC this molecule which is essential for the identity of the
CC organelle, protein sorting and membrane trafficking.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol = ADP +
CC 1-phosphatidyl-1D-myo-inositol 4-phosphate.
CC -!- SUBUNIT: Associates with the BLOC-1 and the AP-3 complexes; the
CC BLOC-1 complex is required for optimal binding of PI4K2A to the
CC AP-3 complex. Interacts with BLOC1S5 and DTNBP1. Interacts with
CC FOS; this interaction may enhance phosphatidylinositol
CC phosphorylation activity (By similarity).
CC -!- INTERACTION:
CC Q96J02:ITCH; NbExp=5; IntAct=EBI-3239392, EBI-1564678;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus, trans-Golgi
CC network membrane; Lipid-anchor. Membrane raft. Cell projection,
CC dendrite (By similarity). Cell junction, synapse, presynaptic cell
CC membrane (By similarity). Cell junction, synapse, synaptosome (By
CC similarity). Mitochondrion (By similarity). Endosome (By
CC similarity). Cytoplasmic vesicle (By similarity). Note=Localized
CC in neuronal cell body. Transported from neuronal cell body to
CC neuron projections in a BLOC-1- and AP-3-complexes-dependent
CC manner. Enriched in neurite tips and neuron projections in a BLOC-
CC 1- and AP-3-complexes-dependent manner (By similarity). Found in
CC subdomains of the plasma membrane termed non-caveolar membrane
CC rafts.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression is
CC observed in kidney, brain, heart, skeletal muscle, and placenta
CC and lowest expression is observed in colon, thymus, and small
CC intestine.
CC -!- PTM: Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif.
CC Palmitoylation is cholesterol-dependent, and required for TGN
CC localization.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC subfamily.
CC -!- SIMILARITY: Contains 1 PI3K/PI4K domain.
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DR EMBL; AJ303098; CAC38065.1; -; mRNA.
DR EMBL; BT007330; AAP35994.1; -; mRNA.
DR EMBL; AL355315; CAI15460.1; -; 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 PIR; T48687; T48687.
DR RefSeq; NP_060895.1; NM_018425.2.
DR UniGene; Hs.25300; -.
DR ProteinModelPortal; Q9BTU6; -.
DR IntAct; Q9BTU6; 4.
DR STRING; 9606.ENSP00000359665; -.
DR BindingDB; Q9BTU6; -.
DR ChEMBL; CHEMBL2096619; -.
DR GuidetoPHARMACOLOGY; 2498; -.
DR PhosphoSite; Q9BTU6; -.
DR DMDM; 74752344; -.
DR PaxDb; Q9BTU6; -.
DR PRIDE; Q9BTU6; -.
DR DNASU; 55361; -.
DR Ensembl; ENST00000370631; ENSP00000359665; ENSG00000155252.
DR GeneID; 55361; -.
DR KEGG; hsa:55361; -.
DR UCSC; uc001kog.1; human.
DR CTD; 55361; -.
DR GeneCards; GC10P099344; -.
DR HGNC; HGNC:30031; PI4K2A.
DR HPA; CAB030649; -.
DR MIM; 609763; gene.
DR neXtProt; NX_Q9BTU6; -.
DR PharmGKB; PA162399304; -.
DR eggNOG; NOG287949; -.
DR HOGENOM; HOG000294076; -.
DR HOVERGEN; HBG059542; -.
DR InParanoid; Q9BTU6; -.
DR KO; K13711; -.
DR OMA; EEGIYPE; -.
DR OrthoDB; EOG7MKW5Z; -.
DR PhylomeDB; Q9BTU6; -.
DR BioCyc; MetaCyc:HS00573-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PI4K2A; human.
DR GeneWiki; PI4K2A; -.
DR GenomeRNAi; 55361; -.
DR NextBio; 59731; -.
DR PRO; PR:Q9BTU6; -.
DR ArrayExpress; Q9BTU6; -.
DR Bgee; Q9BTU6; -.
DR CleanEx; HS_PI4K2A; -.
DR Genevestigator; Q9BTU6; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
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:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0035838; C:growing cell tip; ISS:UniProtKB.
DR GO; GO:0044231; C:host cell presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
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; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; FALSE_NEG.
DR PROSITE; PS00916; PI3_4_KINASE_2; FALSE_NEG.
DR PROSITE; PS50290; PI3_4_KINASE_3; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Endosome; Golgi apparatus; Kinase; Lipoprotein; Membrane;
KW Mitochondrion; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Synapse; Synaptosome; Transferase.
FT CHAIN 1 479 Phosphatidylinositol 4-kinase type 2-
FT alpha.
FT /FTId=PRO_0000285158.
FT DOMAIN 133 438 PI3K/PI4K.
FT COMPBIAS 39 42 Poly-Ala.
FT COMPBIAS 65 97 Ala-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 9 9 Phosphoserine.
FT MOD_RES 47 47 Phosphoserine.
FT MOD_RES 51 51 Phosphoserine.
FT MOD_RES 462 462 Phosphoserine.
FT MOD_RES 464 464 Phosphoserine.
FT LIPID 174 174 S-palmitoyl cysteine (Probable).
FT LIPID 175 175 S-palmitoyl cysteine (Probable).
FT LIPID 177 177 S-palmitoyl cysteine (Probable).
FT LIPID 178 178 S-palmitoyl cysteine (Probable).
FT MUTAGEN 174 178 CCPCC->SSPSS: No interaction with DHHCs
FT and no palmitoylation.
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
//
ID P4K2A_HUMAN Reviewed; 479 AA.
AC Q9BTU6; D3DR59; Q9NSG8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67;
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=PI4K2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
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
RT novel 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
RT 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-462, AND MASS
RP SPECTROMETRY.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-51; SER-462 AND
RP SER-464, AND MASS SPECTROMETRY.
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-5; SER-9 AND SER-47, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
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.,
RA Craige B., 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-51, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
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.,
RA Albanesi J.P., Yin H.L.;
RT "Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-
RT localized palmitoyltransferases in cholesterol-dependent manner.";
RL J. Biol. Chem. 287:21856-21865(2012).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Together with PI4K2B and the type III PI4Ks (PIK4CA and
CC PIK4CB) it contributes to the overall PI4-kinase activity of the
CC cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is
CC the first committed step in the generation of phosphatidylinositol
CC 4,5-bisphosphate (PIP2), a precursor of the second messenger
CC inositol 1,4,5-trisphosphate (InsP3). Contributes to the
CC production of InsP3 in stimulated cells (By similarity). This
CC lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P)
CC producer in the Golgi apparatus, it generates more than 50% of
CC this molecule which is essential for the identity of the
CC organelle, protein sorting and membrane trafficking.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol = ADP +
CC 1-phosphatidyl-1D-myo-inositol 4-phosphate.
CC -!- SUBUNIT: Associates with the BLOC-1 and the AP-3 complexes; the
CC BLOC-1 complex is required for optimal binding of PI4K2A to the
CC AP-3 complex. Interacts with BLOC1S5 and DTNBP1. Interacts with
CC FOS; this interaction may enhance phosphatidylinositol
CC phosphorylation activity (By similarity).
CC -!- INTERACTION:
CC Q96J02:ITCH; NbExp=5; IntAct=EBI-3239392, EBI-1564678;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus, trans-Golgi
CC network membrane; Lipid-anchor. Membrane raft. Cell projection,
CC dendrite (By similarity). Cell junction, synapse, presynaptic cell
CC membrane (By similarity). Cell junction, synapse, synaptosome (By
CC similarity). Mitochondrion (By similarity). Endosome (By
CC similarity). Cytoplasmic vesicle (By similarity). Note=Localized
CC in neuronal cell body. Transported from neuronal cell body to
CC neuron projections in a BLOC-1- and AP-3-complexes-dependent
CC manner. Enriched in neurite tips and neuron projections in a BLOC-
CC 1- and AP-3-complexes-dependent manner (By similarity). Found in
CC subdomains of the plasma membrane termed non-caveolar membrane
CC rafts.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression is
CC observed in kidney, brain, heart, skeletal muscle, and placenta
CC and lowest expression is observed in colon, thymus, and small
CC intestine.
CC -!- PTM: Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif.
CC Palmitoylation is cholesterol-dependent, and required for TGN
CC localization.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC subfamily.
CC -!- SIMILARITY: Contains 1 PI3K/PI4K domain.
CC -----------------------------------------------------------------------
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DR EMBL; AJ303098; CAC38065.1; -; mRNA.
DR EMBL; BT007330; AAP35994.1; -; mRNA.
DR EMBL; AL355315; CAI15460.1; -; 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 PIR; T48687; T48687.
DR RefSeq; NP_060895.1; NM_018425.2.
DR UniGene; Hs.25300; -.
DR ProteinModelPortal; Q9BTU6; -.
DR IntAct; Q9BTU6; 4.
DR STRING; 9606.ENSP00000359665; -.
DR BindingDB; Q9BTU6; -.
DR ChEMBL; CHEMBL2096619; -.
DR GuidetoPHARMACOLOGY; 2498; -.
DR PhosphoSite; Q9BTU6; -.
DR DMDM; 74752344; -.
DR PaxDb; Q9BTU6; -.
DR PRIDE; Q9BTU6; -.
DR DNASU; 55361; -.
DR Ensembl; ENST00000370631; ENSP00000359665; ENSG00000155252.
DR GeneID; 55361; -.
DR KEGG; hsa:55361; -.
DR UCSC; uc001kog.1; human.
DR CTD; 55361; -.
DR GeneCards; GC10P099344; -.
DR HGNC; HGNC:30031; PI4K2A.
DR HPA; CAB030649; -.
DR MIM; 609763; gene.
DR neXtProt; NX_Q9BTU6; -.
DR PharmGKB; PA162399304; -.
DR eggNOG; NOG287949; -.
DR HOGENOM; HOG000294076; -.
DR HOVERGEN; HBG059542; -.
DR InParanoid; Q9BTU6; -.
DR KO; K13711; -.
DR OMA; EEGIYPE; -.
DR OrthoDB; EOG7MKW5Z; -.
DR PhylomeDB; Q9BTU6; -.
DR BioCyc; MetaCyc:HS00573-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PI4K2A; human.
DR GeneWiki; PI4K2A; -.
DR GenomeRNAi; 55361; -.
DR NextBio; 59731; -.
DR PRO; PR:Q9BTU6; -.
DR ArrayExpress; Q9BTU6; -.
DR Bgee; Q9BTU6; -.
DR CleanEx; HS_PI4K2A; -.
DR Genevestigator; Q9BTU6; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
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:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0035838; C:growing cell tip; ISS:UniProtKB.
DR GO; GO:0044231; C:host cell presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
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; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; FALSE_NEG.
DR PROSITE; PS00916; PI3_4_KINASE_2; FALSE_NEG.
DR PROSITE; PS50290; PI3_4_KINASE_3; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Endosome; Golgi apparatus; Kinase; Lipoprotein; Membrane;
KW Mitochondrion; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Synapse; Synaptosome; Transferase.
FT CHAIN 1 479 Phosphatidylinositol 4-kinase type 2-
FT alpha.
FT /FTId=PRO_0000285158.
FT DOMAIN 133 438 PI3K/PI4K.
FT COMPBIAS 39 42 Poly-Ala.
FT COMPBIAS 65 97 Ala-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 9 9 Phosphoserine.
FT MOD_RES 47 47 Phosphoserine.
FT MOD_RES 51 51 Phosphoserine.
FT MOD_RES 462 462 Phosphoserine.
FT MOD_RES 464 464 Phosphoserine.
FT LIPID 174 174 S-palmitoyl cysteine (Probable).
FT LIPID 175 175 S-palmitoyl cysteine (Probable).
FT LIPID 177 177 S-palmitoyl cysteine (Probable).
FT LIPID 178 178 S-palmitoyl cysteine (Probable).
FT MUTAGEN 174 178 CCPCC->SSPSS: No interaction with DHHCs
FT and no palmitoylation.
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
//
MIM
609763
*RECORD*
*FIELD* NO
609763
*FIELD* TI
*609763 PHOSPHATIDYLINOSITOL 4-KINASE, TYPE 2, ALPHA; PI4K2A
;;PHOSPHATIDYLINOSITOL 4-KINASE, TYPE II;;
read morePI4KII;;
PI4KII-ALPHA
*FIELD* TX
DESCRIPTION
Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in
many biologic processes, ranging from cell growth and organization of
the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates
PtdIns at the D-4 position, an essential step in the biosynthesis of
PtdInsPs (Barylko et al., 2001).
CLONING
Minogue et al. (2001) partially purified PI4KII from plasma membrane
rafts isolated from human A431 epidermoid carcinoma cells. By peptide
sequencing, database analysis, and RT-PCR of A431 total RNA, they
obtained a full-length PI4KII cDNA. The deduced 479-amino acid protein
has a calculated molecular mass of about 54 kD. PI4KII has a kinase
domain and a leucine zipper, but no transmembrane sequence or acylation
motif. Northern blot analysis detected a 6.6-kb transcript in all
tissues examined. Expression was highest in kidney, brain, heart,
skeletal muscle, and placenta, and was lowest in colon, thymus, and
small intestine. Purified PI4KII had an apparent molecular mass of 52 kD
by SDS-PAGE.
Barylko et al. (2001) identified a cysteine-rich segment (CCPCC), a
potential palmitoylation site, in rat and human PI4KII.
By immunofluorescence localization, Wang et al. (2003) found that PI4KII
localized to the Golgi in transfected COS-7 cells.
Using microarray analysis, Li et al. (2010) found ubiquitous PI4K-alpha
expression, with higher levels in brain, kidney, stomach, and lung, and
lower levels in thyroid, dermis, breast, and fibrous tissue.
GENE FUNCTION
Minogue et al. (2001) assayed recombinant PI4KII expressed in bacteria
and found that it phosphorylated PtdIns, but not PtdIns3P, PtdIns4P, or
PtdIns5P. Like PI4KII purified from tissues, recombinant PI4KII was
activated by detergent and inhibited by adenosine.
Wang et al. (2003) found that overexpression of PI4KII in COS-7 cells
increased synthesis of PtdIns4P. Some cells overexpressing PI4KII had
scattered or no perinuclear Golgi. Knockdown of PI4KII by RNA
interference (RNAi) did not disrupt the Golgi, and some cells showed
expanded Golgi. RNAi reduced the Golgi level of PtdIns4P and blocked the
association between AP1 (see 607291) and the trans-Golgi network (TGN).
PI4KII RNAi had little effect on intra-Golgi trafficking, but it
inhibited TGN-to-plasma membrane export by 35%. Wang et al. (2003)
proposed that PI4KII generates PtdIns4P-rich domains within the Golgi
that specify docking of the AP1 coat machinery.
By screening a human kinase small interfering RNA library, Pan et al.
(2008) identified PI4KII-alpha and phosphatidylinositol-4-phosphate
5-kinase type I (PIP5KI; 603275) as required for Wnt3a (606359)-induced
LRP6 (603507) phosphorylation at ser1490 in mammalian cells and
confirmed that these kinases are important for Wnt signaling in Xenopus
embryos. Wnt3a stimulates the formation of phosphatidylinositol
4,5-bisphosphates through 'frizzled' (see 603408) and 'dishevelled' (see
601365), the latter of which directly interacted with and activated
PIP5KI. In turn, phosphatidylinositol 4,5-bisphosphates regulated
phosphorylation of LRP6 at thr1479 and ser1490. Pan et al. (2008)
concluded that their study revealed a signaling mechanism for Wnt to
regulate LRP6 phosphorylation.
Li et al. (2010) found that PI4KII-alpha induced angiogenesis in mouse
and human cells via activation of a HER2 (ERBB2; 164870)-PI3K (see
PIK3CG; 601232)-ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948) signaling
cascade, resulting in upregulation of HIF1-alpha (HIF1A; 603348) and
HIF1-alpha-dependent upregulation of VEGF (see VEGFA; 192240) and iNOS
(NOS2A; 163730). Downregulation of PI4KII in HeLa cells via RNA
interference did not cause cell death, but it reduced tumor growth
following inoculation of nude mice. Li et al. (2010) concluded that
PI4KII-alpha can contribute to tumorigenesis via induction of blood
vessel formation under anoxic conditions.
Jovic et al. (2012) found that the PtdIns4P-synthesizing enzymes
PI4KII-alpha and PI4KIII-beta (PI4KB; 602758) had distinct and
sequential roles in the lysosomal delivery of beta-glucosidase (GBA;
606463) and its receptor, LIMP2 (602257). Activity of PI4KIII-beta at
the Golgi was required to drive exit of LIMP2 from the Golgi, whereas
PI4KII-alpha at the trans-Golgi network regulated sorting of LIMP2
toward the late endosome/lysosome compartment. Knockdown or inhibition
of PI3KIII-beta led to accumulation of LIMP2 at the Golgi compartment,
and knockdown of either LIMP2 or PI4KII-alpha increased beta-GC
secretion. Mutations in PI4KII-alpha that disrupted its association with
AP3 (see AP3B1; 603401) disrupted lysosomal LIMP2 targeting.
MAPPING
Gross (2013) mapped the PI4K2A gene to chromosome 10q24.2 based on an
alignment of the PI4K2A sequence (GenBank GENBANK AJ303098) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Barylko, B.; Gerber, S. H.; Binns, D. D.; Grichine, N.; Khvotchev,
M.; Sudhof, T. C.; Albanesi, J. P.: A novel family of phosphatidylinositol
4-kinases conserved from yeast to humans. J. Biol. Chem. 276: 7705-7708,
2001.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 8/7/2013.
3. Jovic, M.; Kean, M. J.; Szentpetery, Z.; Polevoy, G.; Gingras,
A.-C.; Brill, J. A.; Balla, T.: Two phosphatidylinositol 4-kinases
control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase. Molec.
Biol. Cell 23: 1533-1545, 2012.
4. Li, J.; Lu, Y.; Zhang, J.; Kang, H.; Qin, Z.; Chen, C.: PI4KII-alpha
is a novel regulator of tumor growth by its action on angiogenesis
and HIF-1-alpha regulation. Oncogene 29: 2550-2559, 2010.
5. Minogue, S.; Anderson, J. S.; Waugh, M. G.; dos Santos, M.; Corless,
S.; Cramer, R.; Hsuan, J. J.: Cloning of a human type II phosphatidylinositol
4-kinase reveals a novel lipid kinase family. J. Biol. Chem. 276:
16635-16640, 2001.
6. Pan, W.; Choi, S.-C.; Wang, H.; Qin, Y.; Volpicelli-Daley, L.;
Swan, L.; Lucast, L.; Khoo, C.; Zhang, X.; Li, L.; Abrams, C. S.;
Sokol, S. Y.; Wu, D.: Wnt3a-mediated formation of phosphatidylinositol
4,5-bisphosphate regulates LRP6 phosphorylation. Science 321: 1350-1353,
2008.
7. Wang, Y. J.; Wang, J.; Sun, H. Q.; Martinez, M.; Sun, Y. X.; Macia,
E.; Kirchhausen, T.; Albanesi, J. P.; Roth, M. G.; Yin, H. L.: Phosphatidylinositol
4 phosphate regulates targeting of clathrin adaptor AP-1 complexes
to the Golgi. Cell 114: 299-310, 2003.
*FIELD* CN
Matthew B. Gross - updated: 08/07/2013
Patricia A. Hartz - updated: 8/7/2013
Ada Hamosh - updated: 10/2/2008
*FIELD* CD
Patricia A. Hartz: 12/8/2005
*FIELD* ED
mgross: 08/07/2013
mgross: 8/7/2013
alopez: 10/2/2008
carol: 3/18/2008
mgross: 12/8/2005
*RECORD*
*FIELD* NO
609763
*FIELD* TI
*609763 PHOSPHATIDYLINOSITOL 4-KINASE, TYPE 2, ALPHA; PI4K2A
;;PHOSPHATIDYLINOSITOL 4-KINASE, TYPE II;;
read morePI4KII;;
PI4KII-ALPHA
*FIELD* TX
DESCRIPTION
Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in
many biologic processes, ranging from cell growth and organization of
the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates
PtdIns at the D-4 position, an essential step in the biosynthesis of
PtdInsPs (Barylko et al., 2001).
CLONING
Minogue et al. (2001) partially purified PI4KII from plasma membrane
rafts isolated from human A431 epidermoid carcinoma cells. By peptide
sequencing, database analysis, and RT-PCR of A431 total RNA, they
obtained a full-length PI4KII cDNA. The deduced 479-amino acid protein
has a calculated molecular mass of about 54 kD. PI4KII has a kinase
domain and a leucine zipper, but no transmembrane sequence or acylation
motif. Northern blot analysis detected a 6.6-kb transcript in all
tissues examined. Expression was highest in kidney, brain, heart,
skeletal muscle, and placenta, and was lowest in colon, thymus, and
small intestine. Purified PI4KII had an apparent molecular mass of 52 kD
by SDS-PAGE.
Barylko et al. (2001) identified a cysteine-rich segment (CCPCC), a
potential palmitoylation site, in rat and human PI4KII.
By immunofluorescence localization, Wang et al. (2003) found that PI4KII
localized to the Golgi in transfected COS-7 cells.
Using microarray analysis, Li et al. (2010) found ubiquitous PI4K-alpha
expression, with higher levels in brain, kidney, stomach, and lung, and
lower levels in thyroid, dermis, breast, and fibrous tissue.
GENE FUNCTION
Minogue et al. (2001) assayed recombinant PI4KII expressed in bacteria
and found that it phosphorylated PtdIns, but not PtdIns3P, PtdIns4P, or
PtdIns5P. Like PI4KII purified from tissues, recombinant PI4KII was
activated by detergent and inhibited by adenosine.
Wang et al. (2003) found that overexpression of PI4KII in COS-7 cells
increased synthesis of PtdIns4P. Some cells overexpressing PI4KII had
scattered or no perinuclear Golgi. Knockdown of PI4KII by RNA
interference (RNAi) did not disrupt the Golgi, and some cells showed
expanded Golgi. RNAi reduced the Golgi level of PtdIns4P and blocked the
association between AP1 (see 607291) and the trans-Golgi network (TGN).
PI4KII RNAi had little effect on intra-Golgi trafficking, but it
inhibited TGN-to-plasma membrane export by 35%. Wang et al. (2003)
proposed that PI4KII generates PtdIns4P-rich domains within the Golgi
that specify docking of the AP1 coat machinery.
By screening a human kinase small interfering RNA library, Pan et al.
(2008) identified PI4KII-alpha and phosphatidylinositol-4-phosphate
5-kinase type I (PIP5KI; 603275) as required for Wnt3a (606359)-induced
LRP6 (603507) phosphorylation at ser1490 in mammalian cells and
confirmed that these kinases are important for Wnt signaling in Xenopus
embryos. Wnt3a stimulates the formation of phosphatidylinositol
4,5-bisphosphates through 'frizzled' (see 603408) and 'dishevelled' (see
601365), the latter of which directly interacted with and activated
PIP5KI. In turn, phosphatidylinositol 4,5-bisphosphates regulated
phosphorylation of LRP6 at thr1479 and ser1490. Pan et al. (2008)
concluded that their study revealed a signaling mechanism for Wnt to
regulate LRP6 phosphorylation.
Li et al. (2010) found that PI4KII-alpha induced angiogenesis in mouse
and human cells via activation of a HER2 (ERBB2; 164870)-PI3K (see
PIK3CG; 601232)-ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948) signaling
cascade, resulting in upregulation of HIF1-alpha (HIF1A; 603348) and
HIF1-alpha-dependent upregulation of VEGF (see VEGFA; 192240) and iNOS
(NOS2A; 163730). Downregulation of PI4KII in HeLa cells via RNA
interference did not cause cell death, but it reduced tumor growth
following inoculation of nude mice. Li et al. (2010) concluded that
PI4KII-alpha can contribute to tumorigenesis via induction of blood
vessel formation under anoxic conditions.
Jovic et al. (2012) found that the PtdIns4P-synthesizing enzymes
PI4KII-alpha and PI4KIII-beta (PI4KB; 602758) had distinct and
sequential roles in the lysosomal delivery of beta-glucosidase (GBA;
606463) and its receptor, LIMP2 (602257). Activity of PI4KIII-beta at
the Golgi was required to drive exit of LIMP2 from the Golgi, whereas
PI4KII-alpha at the trans-Golgi network regulated sorting of LIMP2
toward the late endosome/lysosome compartment. Knockdown or inhibition
of PI3KIII-beta led to accumulation of LIMP2 at the Golgi compartment,
and knockdown of either LIMP2 or PI4KII-alpha increased beta-GC
secretion. Mutations in PI4KII-alpha that disrupted its association with
AP3 (see AP3B1; 603401) disrupted lysosomal LIMP2 targeting.
MAPPING
Gross (2013) mapped the PI4K2A gene to chromosome 10q24.2 based on an
alignment of the PI4K2A sequence (GenBank GENBANK AJ303098) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Barylko, B.; Gerber, S. H.; Binns, D. D.; Grichine, N.; Khvotchev,
M.; Sudhof, T. C.; Albanesi, J. P.: A novel family of phosphatidylinositol
4-kinases conserved from yeast to humans. J. Biol. Chem. 276: 7705-7708,
2001.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 8/7/2013.
3. Jovic, M.; Kean, M. J.; Szentpetery, Z.; Polevoy, G.; Gingras,
A.-C.; Brill, J. A.; Balla, T.: Two phosphatidylinositol 4-kinases
control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase. Molec.
Biol. Cell 23: 1533-1545, 2012.
4. Li, J.; Lu, Y.; Zhang, J.; Kang, H.; Qin, Z.; Chen, C.: PI4KII-alpha
is a novel regulator of tumor growth by its action on angiogenesis
and HIF-1-alpha regulation. Oncogene 29: 2550-2559, 2010.
5. Minogue, S.; Anderson, J. S.; Waugh, M. G.; dos Santos, M.; Corless,
S.; Cramer, R.; Hsuan, J. J.: Cloning of a human type II phosphatidylinositol
4-kinase reveals a novel lipid kinase family. J. Biol. Chem. 276:
16635-16640, 2001.
6. Pan, W.; Choi, S.-C.; Wang, H.; Qin, Y.; Volpicelli-Daley, L.;
Swan, L.; Lucast, L.; Khoo, C.; Zhang, X.; Li, L.; Abrams, C. S.;
Sokol, S. Y.; Wu, D.: Wnt3a-mediated formation of phosphatidylinositol
4,5-bisphosphate regulates LRP6 phosphorylation. Science 321: 1350-1353,
2008.
7. Wang, Y. J.; Wang, J.; Sun, H. Q.; Martinez, M.; Sun, Y. X.; Macia,
E.; Kirchhausen, T.; Albanesi, J. P.; Roth, M. G.; Yin, H. L.: Phosphatidylinositol
4 phosphate regulates targeting of clathrin adaptor AP-1 complexes
to the Golgi. Cell 114: 299-310, 2003.
*FIELD* CN
Matthew B. Gross - updated: 08/07/2013
Patricia A. Hartz - updated: 8/7/2013
Ada Hamosh - updated: 10/2/2008
*FIELD* CD
Patricia A. Hartz: 12/8/2005
*FIELD* ED
mgross: 08/07/2013
mgross: 8/7/2013
alopez: 10/2/2008
carol: 3/18/2008
mgross: 12/8/2005