P4K2A_DANRE
ID P4K2A_DANRE Reviewed; 447 AA.
AC Q6PE18; A5PF25; Q52PF3;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Phosphatidylinositol 4-kinase type 2-alpha;
DE EC=2.7.1.67 {ECO:0000250|UniProtKB:Q9BTU6};
DE AltName: Full=Phosphatidylinositol 4-kinase type II-alpha;
GN Name=pi4k2a; Synonyms=pi4kii; ORFNames=si:ch211-197k17.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ma H., Balla T.;
RT "Phosphatidylinositol 4-kinases of Danio rerio.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=SJD;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 105-447.
RA Rafael M.S., Laize V., Cancela M.L.;
RT "Cloning of Danio rerio phosphatidylinositol 4-kinase type II partial
RT cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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. Besides, phosphorylation of phosphatidylinositol (PI) to
CC phosphatidylinositol 4-phosphate (PI4P) is the first committed step in
CC the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a
CC precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).
CC {ECO:0000250|UniProtKB:Q9BTU6}.
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:0000250|UniProtKB:Q9BTU6};
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: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
CC {ECO:0000250|UniProtKB:Q2TBE6}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9BTU6}. Perikaryon
CC {ECO:0000250|UniProtKB:Q2TBE6}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q2TBE6}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC subfamily. {ECO:0000305}.
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DR EMBL; AY929290; AAY16565.1; -; mRNA.
DR EMBL; AL929041; CAN88146.1; -; Genomic_DNA.
DR EMBL; BX119918; CAN88146.1; JOINED; Genomic_DNA.
DR EMBL; BC058342; AAH58342.1; -; mRNA.
DR EMBL; AY989909; AAX89135.1; -; mRNA.
DR RefSeq; NP_998523.1; NM_213358.1.
DR AlphaFoldDB; Q6PE18; -.
DR SMR; Q6PE18; -.
DR STRING; 7955.ENSDARP00000112458; -.
DR PaxDb; Q6PE18; -.
DR PRIDE; Q6PE18; -.
DR Ensembl; ENSDART00000130675; ENSDARP00000112458; ENSDARG00000033666.
DR Ensembl; ENSDART00000162075; ENSDARP00000140323; ENSDARG00000033666.
DR GeneID; 406667; -.
DR KEGG; dre:406667; -.
DR CTD; 55361; -.
DR ZFIN; ZDB-GENE-040426-2675; pi4k2a.
DR eggNOG; KOG2381; Eukaryota.
DR GeneTree; ENSGT00390000010434; -.
DR HOGENOM; CLU_032516_1_0_1; -.
DR InParanoid; Q6PE18; -.
DR OMA; YIIRNTX; -.
DR OrthoDB; 1273723at2759; -.
DR PhylomeDB; Q6PE18; -.
DR TreeFam; TF314740; -.
DR Reactome; R-DRE-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-DRE-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-DRE-1660516; Synthesis of PIPs at the early endosome membrane.
DR PRO; PR:Q6PE18; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000033666; Expressed in mature ovarian follicle and 25 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
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:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
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; 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; IBA:GO_Central.
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; 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: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; 2.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Cell projection; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; Kinase; Lipid metabolism; Lipoprotein; Membrane;
KW Mitochondrion; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Synapse; Synaptosome; Transferase.
FT CHAIN 1..447
FT /note="Phosphatidylinositol 4-kinase type 2-alpha"
FT /id="PRO_0000285161"
FT DOMAIN 92..421
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..104
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 125..127
FT /note="Important for substrate binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 133..146
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 236..244
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT REGION 273..281
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 312..332
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 327..336
FT /note="Important for interaction with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT COMPBIAS 51..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 99..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 229..232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT BINDING 314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT LIPID 142
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 143
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 145
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 146
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CONFLICT 255
FT /note="N -> S (in Ref. 4; AAX89135)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 51443 MW; 305A7326FF293865 CRC64;
MDETSPLVSP LRDSNDFNYG PAEPTSPRGG FGSTPGSVVR LPAGSPGRSR ERQPLLDRDR
GASPRDPHRN EFPEDPEFRE IIRKAERAIE EGIYPERIYQ GSSGSYFVKD SAGKIIGVFK
PKNEEPYGQL NPKWTKWLQK LCCPCCFGRD CLVLNQGYLS EAGASLVDQK LELNIVPRTK
VVYLASETFN YSAIDRVKSR GKRLALEKVP KVGQRFHRIG LPPKVGSFQI FVEGYKDADF
WLRRFEAEPL PENTNRQLQL QFERLVVLDY IIRNTDRGND NWLIKYDYPM DTSSNRDSDW
VLVKDPIIKL AAIDNGLAFP LKHPDSWRAY PFYWAWLPQA KVVFSQEIRD LVLPKLADPN
FIKDLEEDLY ELFKKDPGFD RGQFKKQVSV MRGQILNLSQ AMRDGKTPLQ LVQMPPVIVE
TARVPQRANS ESYTQSFQSR RPFFTWW
