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Protein

Phosphatidylinositol 4-kinase type 2-alpha

Gene

Pi4k2a

Organism
Mus musculus (Mouse)
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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei152 – 1521ATPBy similarity
Binding sitei346 – 3461ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi131 – 1377ATPBy similarity
Nucleotide bindingi261 – 2644ATPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1934031. 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: Ensembl
  • endosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB-SubCell
  • growing cell tip Source: UniProtKB
  • host cell presynaptic membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intrinsic component of membrane Source: UniProtKB
  • lysosomal membrane Source: MGI
  • membrane Source: MGI
  • membrane raft Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perikaryon Source: Ensembl
  • presynaptic membrane Source: UniProtKB
  • synaptic vesicle membrane Source: Ensembl
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 479479Phosphatidylinositol 4-kinase type 2-alphaPRO_0000285159Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei5 – 51PhosphoserineBy similarity
Modified residuei9 – 91PhosphoserineBy similarity
Modified residuei44 – 441PhosphoserineBy similarity
Modified residuei47 – 471PhosphoserineCombined sources
Modified residuei51 – 511PhosphoserineCombined sources
Lipidationi174 – 1741S-palmitoyl cysteineBy similarity
Lipidationi175 – 1751S-palmitoyl cysteineBy similarity
Lipidationi177 – 1771S-palmitoyl cysteineBy similarity
Lipidationi178 – 1781S-palmitoyl cysteineBy similarity
Modified residuei462 – 4621PhosphoserineBy similarity

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.
PhosphoSiteiQ2TBE6.
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220002. 20 interactions.
IntActiQ2TBE6. 5 interactions.
STRINGi10090.ENSMUSP00000069284.

Structurei

3D structure databases

ProteinModelPortaliQ2TBE6.
SMRiQ2TBE6. Positions 98-453.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini133 – 438306PI3K/PI4KAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni157 – 1593Important for substrate bindingBy similarity
Regioni165 – 17814Important for interaction with membranesBy similarityAdd
BLAST
Regioni268 – 2769Important for interaction with membranesBy similarity
Regioni359 – 36810Important for interaction with membranesBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi39 – 424Poly-Ala

Sequence similaritiesi

Contains 1 PI3K/PI4K domain.Curated

Phylogenomic databases

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

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_011247405.1.
UniGeneiMm.117037.

Genome annotation databases

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

Cross-referencesi

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_011247405.1.
UniGeneiMm.117037.

3D structure databases

ProteinModelPortaliQ2TBE6.
SMRiQ2TBE6. Positions 98-453.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi220002. 20 interactions.
IntActiQ2TBE6. 5 interactions.
STRINGi10090.ENSMUSP00000069284.

PTM databases

iPTMnetiQ2TBE6.
PhosphoSiteiQ2TBE6.
SwissPalmiQ2TBE6.

Proteomic databases

EPDiQ2TBE6.
MaxQBiQ2TBE6.
PaxDbiQ2TBE6.
PeptideAtlasiQ2TBE6.
PRIDEiQ2TBE6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi55361.
MGIiMGI:1934031. Pi4k2a.

Phylogenomic databases

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

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.

Miscellaneous databases

PROiQ2TBE6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025178.
CleanExiMM_PI4K2A.
GenevisibleiQ2TBE6. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q2TBE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 16, 2006
Last modified: September 7, 2016
This is version 91 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.