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Protein

Phosphatidylinositol 4-kinase type 2-alpha

Gene

Pi4k2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei152ATPBy similarity1
Binding sitei346ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi131 – 137ATPBy similarity7
Nucleotide bindingi261 – 264ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-1660514 Synthesis of PIPs at the Golgi membrane
R-MMU-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):
Phosphatidylinositol 4-kinase type II-alpha
Gene namesi
Name:Pi4k2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1934031 Pi4k2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mice are born at the expected Mendelian rate. Young animals have no visible phenotype, but oldeer mice develop urinary incontinence, head tremor, spastic gait, weakness of the hind limbs, followed by additional weakness of the forelimbs, weight loss and premature death. Their brains show no gross anatomical defects, but show loss of Purkinje cells. In addition, mice present massive axon degeneration in the ascending and descending tract of the spinal cord. Male mice are infertile and females are subfertile.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002851591 – 479Phosphatidylinositol 4-kinase type 2-alphaAdd BLAST479

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei5PhosphoserineBy similarity1
Modified residuei9PhosphoserineBy similarity1
Modified residuei44PhosphoserineBy similarity1
Modified residuei47PhosphoserineCombined sources1
Modified residuei51PhosphoserineCombined sources1
Lipidationi174S-palmitoyl cysteineBy similarity1
Lipidationi175S-palmitoyl cysteineBy similarity1
Lipidationi177S-palmitoyl cysteineBy similarity1
Lipidationi178S-palmitoyl cysteineBy similarity1
Modified residuei462PhosphoserineBy similarity1

Post-translational modificationi

Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif. Palmitoylation is cholesterol-dependent, and required for TGN localization (By similarity).By similarity
Ubiquitinated by ITCH; this does not lead to proteasomal degradation.1 Publication

Keywords - PTMi

Acetylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ2TBE6
MaxQBiQ2TBE6
PaxDbiQ2TBE6
PeptideAtlasiQ2TBE6
PRIDEiQ2TBE6

PTM databases

iPTMnetiQ2TBE6
PhosphoSitePlusiQ2TBE6
SwissPalmiQ2TBE6

Expressioni

Tissue specificityi

Detected in brain (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000025178
CleanExiMM_PI4K2A
GenevisibleiQ2TBE6 MM

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 (PubMed:21998198). Interacts with BLOC1S5 and DTNBP1 (By similarity). Interacts with ITCH (PubMed:23146885). Interacts with FOS; this interaction may enhance phosphatidylinositol phosphorylation activity (PubMed:22105363).By similarity3 Publications

Protein-protein interaction databases

BioGridi220002, 20 interactors
IntActiQ2TBE6, 5 interactors
MINTiQ2TBE6
STRINGi10090.ENSMUSP00000069284

Structurei

3D structure databases

ProteinModelPortaliQ2TBE6
SMRiQ2TBE6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini133 – 438PI3K/PI4KAdd BLAST306

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni157 – 159Important for substrate bindingBy similarity3
Regioni165 – 178Important for interaction with membranesBy similarityAdd BLAST14
Regioni268 – 276Important for interaction with membranesBy similarity9
Regioni359 – 368Important for interaction with membranesBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi39 – 42Poly-Ala4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2381 Eukaryota
ENOG410XP06 LUCA
GeneTreeiENSGT00390000010434
HOGENOMiHOG000294076
HOVERGENiHBG059542
InParanoidiQ2TBE6
KOiK13711
OMAiGVRDSDW
OrthoDBiEOG091G09F3
PhylomeDBiQ2TBE6
TreeFamiTF314740

Family and domain databases

InterProiView protein in InterPro
IPR000403 PI3/4_kinase_cat_dom
PfamiView protein in Pfam
PF00454 PI3_PI4_kinase, 1 hit

Sequencei

Sequence statusi: Complete.

Q2TBE6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDETSPLVSP ERAQPPEYTF PSGSGAHFPQ VPGGAVRVAA AAGSGPSPPC
60 70 80 90 100
SPGHDRERQP LLDRARGAAA QGQTHTVAVQ AQALAAQAAV AAHAVQTHRE
110 120 130 140 150
RNDFPEDPEF EVVVRQAEVA IECSIYPERI YQGSSGSYFV KDSQGRIVAV
160 170 180 190 200
FKPKNEEPYG HLNPKWTKWL QKLCCPCCFG RDCLVLNQGY LSEAGASLVD
210 220 230 240 250
QKLELNIVPR TKVVYLASET FNYSAIDRVK SRGKRLALEK VPKVGQRFNR
260 270 280 290 300
IGLPPKVGSF QLFVEGYKDA DYWLRRFEAE PLPENTNRQL LLQFERLVVL
310 320 330 340 350
DYIIRNTDRG NDNWLIKYDC PMDNSSCRDT DWVMVREPVI KVAAIDNGLA
360 370 380 390 400
FPLKHPDSWR AYPFYWAWLP QAKVPFSQEI KDLILPKISD PNFIKDLEED
410 420 430 440 450
LYELFKRDPG FDRGQFHKQI AVMRGQILNL TQALKDNKSP LHLVQMPPVI
460 470
VETARSHQRS ASESYTQSFQ SRKPFFSWW
Length:479
Mass (Da):54,258
Last modified:May 16, 2006 - v1
Checksum:i1D7429AA7BF2918B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC110363 mRNA Translation: AAI10364.1
CCDSiCCDS29821.1
RefSeqiNP_663476.1, NM_145501.2
XP_011245707.1, XM_011247405.2
UniGeneiMm.117037

Genome annotation databases

EnsembliENSMUST00000066778; ENSMUSP00000069284; ENSMUSG00000025178
GeneIDi84095
KEGGimmu:84095
UCSCiuc008hnf.1 mouse

Similar proteinsi

Entry informationi

Entry nameiP4K2A_MOUSE
AccessioniPrimary (citable) accession number: Q2TBE6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 16, 2006
Last modified: March 28, 2018
This is version 104 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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