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Protein

Phosphatidylinositol 4-kinase type 2-alpha

Gene

Pi4k2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Membrane-bound phosphatidylinositol-4 kinase (PI4-kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking and is required for prolonged survival of neurons. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).Curated1 Publication

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate.1 Publication

Kineticsi

  1. KM=88 µM for ATP
  2. KM=45 µM for PtdIns

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei151ATPBy similarity1
    Binding sitei345ATPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi130 – 136ATPBy similarity7
    Nucleotide bindingi260 – 263ATPBy similarity4

    GO - Molecular functioni

    • 1-phosphatidylinositol 4-kinase activity Source: RGD
    • AP-3 adaptor complex binding Source: UniProtKB
    • ATP binding Source: UniProtKB
    • protein complex binding Source: RGD

    GO - Biological processi

    • basophil degranulation Source: RGD
    • mitophagy in response to mitochondrial depolarization Source: Ensembl
    • phosphatidylinositol biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-RNO-1660499. Synthesis of PIPs at the plasma membrane.
    R-RNO-1660514. Synthesis of PIPs at the Golgi membrane.
    R-RNO-1660516. Synthesis of PIPs at the early endosome membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 4-kinase type 2-alpha (EC:2.7.1.671 Publication)
    Alternative name(s):
    55 kDa type II phosphatidylinositol 4-kinase
    Phosphatidylinositol 4-kinase type II-alpha
    Gene namesi
    Name:Pi4k2a
    Synonyms:Pi4kii
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 1

    Organism-specific databases

    RGDi620485. Pi4k2a.

    Subcellular locationi

    GO - Cellular componenti

    • BLOC-1 complex Source: Ensembl
    • cell junction Source: UniProtKB-KW
    • cytoplasmic vesicle Source: UniProtKB
    • dendrite Source: UniProtKB
    • early endosome membrane Source: RGD
    • endosome Source: UniProtKB
    • exocytic vesicle Source: RGD
    • Golgi apparatus Source: UniProtKB-SubCell
    • growing cell tip Source: UniProtKB
    • host cell presynaptic membrane Source: UniProtKB
    • integral component of plasma membrane Source: UniProtKB
    • intracellular membrane-bounded organelle Source: RGD
    • intrinsic component of membrane Source: UniProtKB
    • lysosomal membrane Source: Ensembl
    • membrane raft Source: RGD
    • mitochondrion Source: UniProtKB
    • neuronal cell body Source: UniProtKB
    • neuron projection Source: UniProtKB
    • perikaryon Source: RGD
    • plasma membrane Source: RGD
    • presynaptic membrane Source: UniProtKB
    • protein complex Source: RGD
    • synaptic vesicle membrane Source: RGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Golgi apparatus, Membrane, Mitochondrion, Synapse, Synaptosome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi60L → A: Reduces targeting to synaptic vesicles and neurite tips; when associated with A-61. 1 Publication1
    Mutagenesisi61L → A: Reduces targeting to synaptic vesicles and neurite tips; when associated with A-60. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002851601 – 478Phosphatidylinositol 4-kinase type 2-alphaAdd BLAST478

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineBy similarity1
    Modified residuei5PhosphoserineCombined sources1
    Modified residuei9PhosphoserineCombined sources1
    Modified residuei43PhosphoserineBy similarity1
    Modified residuei46PhosphoserineCombined sources1
    Modified residuei50PhosphoserineCombined sources1
    Lipidationi173S-palmitoyl cysteineBy similarity1
    Lipidationi174S-palmitoyl cysteineBy similarity1
    Lipidationi176S-palmitoyl cysteineBy similarity1
    Lipidationi177S-palmitoyl cysteineBy similarity1
    Modified residuei461PhosphoserineCombined sources1

    Post-translational modificationi

    Ubiquitinated by ITCH; this does not lead to proteasomal degradation.By similarity
    Palmitoylated (PubMed:11244087). Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif. Palmitoylation is cholesterol-dependent, and required for TGN localization (By similarity).By similarity1 Publication

    Keywords - PTMi

    Acetylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ99M64.
    PRIDEiQ99M64.

    PTM databases

    iPTMnetiQ99M64.
    PhosphoSitePlusiQ99M64.
    SwissPalmiQ99M64.

    Expressioni

    Tissue specificityi

    Detected in adult brain, especially in neurons in the cerebellum, brain cortex, dorsal root ganglion and spinal cord (at protein level).1 Publication

    Gene expression databases

    BgeeiENSRNOG00000014675.
    GenevisibleiQ99M64. RN.

    Interactioni

    Subunit structurei

    Associates with the BLOC-1 and the AP-3 complexes; the BLOC-1 complex is required for optimal binding of PI4K2A to the AP-3 complex. Interacts with BLOC1S5 and DTNBP1 (PubMed:21998198). Interacts with FOS; this interaction may enhance phosphatidylinositol phosphorylation activity (By similarity). Interacts with ITCH (By similarity).By similarity1 Publication

    GO - Molecular functioni

    • AP-3 adaptor complex binding Source: UniProtKB
    • protein complex binding Source: RGD

    Protein-protein interaction databases

    BioGridi250373. 1 interactor.
    IntActiQ99M64. 2 interactors.
    STRINGi10116.ENSRNOP00000019874.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini132 – 437PI3K/PI4KAdd BLAST306

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni156 – 158Important for substrate bindingBy similarity3
    Regioni164 – 177Important for interaction with membranesBy similarityAdd BLAST14
    Regioni267 – 275Important for interaction with membranesBy similarity9
    Regioni358 – 367Important for interaction with membranesBy similarity10

    Sequence similaritiesi

    Contains 1 PI3K/PI4K domain.Curated

    Phylogenomic databases

    eggNOGiKOG2381. Eukaryota.
    ENOG410XP06. LUCA.
    GeneTreeiENSGT00390000010434.
    HOGENOMiHOG000294076.
    HOVERGENiHBG059542.
    InParanoidiQ99M64.
    KOiK13711.
    OMAiGVRDSDW.
    OrthoDBiEOG091G09F3.
    PhylomeDBiQ99M64.
    TreeFamiTF314740.

    Family and domain databases

    InterProiIPR000403. PI3/4_kinase_cat_dom.
    [Graphical view]
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q99M64-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MDETSPLVSP ERAQPPEYTF PSVSGAHFPQ VPGGAVRVAA AGSGPSPPCS
    60 70 80 90 100
    PGHDRERQPL LDRARGAAAQ GQTHTVAAQA QALAAQAAVA VHAVQTHRER
    110 120 130 140 150
    NDFPEDPEFE VVVRQAEIAI ECSIYPERIY QGSSGSYFVK DSQGRIIAVF
    160 170 180 190 200
    KPKNEEPYGN LNPKWTKWLQ KLCCPCCFGR DCLVLNQGYL SEAGASLVDQ
    210 220 230 240 250
    KLELNIVPRT KVVYLASETF NYSAIDRVKS RGKRLALEKV PKVGQRFNRI
    260 270 280 290 300
    GLPPKVGSFQ LFVEGYKDAD YWLRRFEAEP LPENTNRQLL LQFERLVVLD
    310 320 330 340 350
    YIIRNTDRGN DNWLIKYDYP MDNPNCRDTD WVMVREPVIK VAAIDNGLAF
    360 370 380 390 400
    PLKHPDSWRA YPFYWAWLPQ AKVPFSQEIK DLILPKISDP NFVKDLEEDL
    410 420 430 440 450
    YELFKKDPGF DRGQFHKQIA VMRGQILNLT QALKDNKSPL HLVQMPPVIV
    460 470
    ETARSHQRSS SESYTQSFQS RKPFFSWW
    Length:478
    Mass (Da):54,305
    Last modified:June 1, 2001 - v1
    Checksum:iEBE4BFFB4574FD1F
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY029199 mRNA. Translation: AAK33002.1.
    RefSeqiNP_446187.1. NM_053735.1.
    UniGeneiRn.162533.

    Genome annotation databases

    EnsembliENSRNOT00000019874; ENSRNOP00000019874; ENSRNOG00000014675.
    GeneIDi114554.
    KEGGirno:114554.
    UCSCiRGD:620485. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY029199 mRNA. Translation: AAK33002.1.
    RefSeqiNP_446187.1. NM_053735.1.
    UniGeneiRn.162533.

    3D structure databases

    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi250373. 1 interactor.
    IntActiQ99M64. 2 interactors.
    STRINGi10116.ENSRNOP00000019874.

    PTM databases

    iPTMnetiQ99M64.
    PhosphoSitePlusiQ99M64.
    SwissPalmiQ99M64.

    Proteomic databases

    PaxDbiQ99M64.
    PRIDEiQ99M64.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000019874; ENSRNOP00000019874; ENSRNOG00000014675.
    GeneIDi114554.
    KEGGirno:114554.
    UCSCiRGD:620485. rat.

    Organism-specific databases

    CTDi55361.
    RGDi620485. Pi4k2a.

    Phylogenomic databases

    eggNOGiKOG2381. Eukaryota.
    ENOG410XP06. LUCA.
    GeneTreeiENSGT00390000010434.
    HOGENOMiHOG000294076.
    HOVERGENiHBG059542.
    InParanoidiQ99M64.
    KOiK13711.
    OMAiGVRDSDW.
    OrthoDBiEOG091G09F3.
    PhylomeDBiQ99M64.
    TreeFamiTF314740.

    Enzyme and pathway databases

    ReactomeiR-RNO-1660499. Synthesis of PIPs at the plasma membrane.
    R-RNO-1660514. Synthesis of PIPs at the Golgi membrane.
    R-RNO-1660516. Synthesis of PIPs at the early endosome membrane.

    Miscellaneous databases

    PROiQ99M64.

    Gene expression databases

    BgeeiENSRNOG00000014675.
    GenevisibleiQ99M64. RN.

    Family and domain databases

    InterProiIPR000403. PI3/4_kinase_cat_dom.
    [Graphical view]
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiP4K2A_RAT
    AccessioniPrimary (citable) accession number: Q99M64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 2007
    Last sequence update: June 1, 2001
    Last modified: November 2, 2016
    This is version 94 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.