UniProtKB - Q99M64 (P4K2A_RAT)
Phosphatidylinositol 4-kinase type 2-alpha
Pi4k2a
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 PublicationCatalytic activityi
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ADP + H+1 PublicationEC:2.7.1.671 Publication
Kineticsi
- KM=88 µM for ATP
- KM=45 µM for PtdIns
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 151 | ATPBy similarity | 1 | |
Binding sitei | 345 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 130 – 136 | ATPBy similarity | 7 | |
Nucleotide bindingi | 260 – 263 | ATPBy similarity | 4 |
GO - Molecular functioni
- 1-phosphatidylinositol 4-kinase activity Source: RGD
- AP-3 adaptor complex binding Source: UniProtKB
- ATP binding Source: UniProtKB
- protein-containing complex binding Source: RGD
GO - Biological processi
- basophil degranulation Source: RGD
- endosome organization Source: GO_Central
- Golgi organization Source: GO_Central
- phosphatidylinositol biosynthetic process Source: UniProtKB
- phosphatidylinositol phosphate biosynthetic process Source: RGD
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-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 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 620485, Pi4k2a |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Plasma membrane
- presynaptic cell membrane By similarity
- Cell membrane By similarity
Endosome
- Endosome 1 Publication
Golgi apparatus
- trans-Golgi network membrane By similarity; Lipid-anchor By similarity
Other locations
- Membrane raft By similarity
- Cytoplasmic vesicle 1 Publication
- dendrite By similarity
- synaptosome By similarity
- Membrane 1 Publication; Lipid-anchor 1 Publication
- Perikaryon By similarity
- neuron projection By similarity
Note: Found in subdomains of the plasma membrane termed non-caveolar membrane rafts. Transported from neuronal cell body to neuron projections and neurite tips in a BLOC-1- and AP-3-complexes-dependent manner.By similarity
Endosome
- early endosome membrane Source: RGD
- endosome Source: UniProtKB
Golgi apparatus
- trans-Golgi network Source: GO_Central
Mitochondrion
- mitochondrion Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: RGD
- presynaptic membrane Source: UniProtKB
Other locations
- cytoplasmic vesicle Source: UniProtKB
- dendrite Source: UniProtKB
- exocytic vesicle Source: RGD
- growing cell tip Source: UniProtKB
- intracellular membrane-bounded organelle Source: RGD
- intrinsic component of membrane Source: UniProtKB
- membrane raft Source: RGD
- neuron projection Source: UniProtKB
- neuronal cell body Source: UniProtKB
- perikaryon Source: RGD
- protein-containing complex Source: RGD
- synaptic vesicle membrane Source: RGD
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Golgi apparatus, Membrane, Mitochondrion, Synapse, SynaptosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 60 | L → A: Reduces targeting to synaptic vesicles and neurite tips; when associated with A-61. 1 Publication | 1 | |
Mutagenesisi | 61 | L → A: Reduces targeting to synaptic vesicles and neurite tips; when associated with A-60. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000285160 | 1 – 478 | Phosphatidylinositol 4-kinase type 2-alphaAdd BLAST | 478 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 5 | PhosphoserineCombined sources | 1 | |
Modified residuei | 9 | PhosphoserineCombined sources | 1 | |
Modified residuei | 43 | PhosphoserineBy similarity | 1 | |
Modified residuei | 46 | PhosphoserineCombined sources | 1 | |
Modified residuei | 50 | PhosphoserineCombined sources | 1 | |
Lipidationi | 173 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 174 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 176 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 177 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 461 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q99M64 |
PaxDbi | Q99M64 |
PRIDEi | Q99M64 |
PTM databases
iPTMneti | Q99M64 |
PhosphoSitePlusi | Q99M64 |
SwissPalmi | Q99M64 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSRNOG00000014675, Expressed in cerebellum and 20 other tissues |
Genevisiblei | Q99M64, 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).
Interacts with ATG9A (By similarity).
By similarity1 PublicationProtein-protein interaction databases
BioGRIDi | 250373, 1 interactor |
IntActi | Q99M64, 3 interactors |
MINTi | Q99M64 |
STRINGi | 10116.ENSRNOP00000019874 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 123 – 452 | PI3K/PI4K catalyticPROSITE-ProRule annotationAdd BLAST | 330 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 57 | DisorderedSequence analysisAdd BLAST | 57 | |
Regioni | 129 – 135 | G-loopPROSITE-ProRule annotation | 7 | |
Regioni | 156 – 158 | Important for substrate bindingBy similarity | 3 | |
Regioni | 164 – 177 | Important for interaction with membranesBy similarityAdd BLAST | 14 | |
Regioni | 267 – 275 | Important for interaction with membranesBy similarity | 9 | |
Regioni | 304 – 312 | Catalytic loopPROSITE-ProRule annotation | 9 | |
Regioni | 343 – 363 | Activation loopPROSITE-ProRule annotationAdd BLAST | 21 | |
Regioni | 358 – 367 | Important for interaction with membranesBy similarity | 10 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2381, Eukaryota |
GeneTreei | ENSGT00390000010434 |
HOGENOMi | CLU_032516_2_0_1 |
InParanoidi | Q99M64 |
OMAi | CLIPLNG |
OrthoDBi | 1273723at2759 |
PhylomeDBi | Q99M64 |
TreeFami | TF314740 |
Family and domain databases
InterProi | View protein in InterPro IPR039756, Lsb6/PI4K2 IPR000403, PI3/4_kinase_cat_dom |
PANTHERi | PTHR12865, PTHR12865, 1 hit |
Pfami | View protein in Pfam PF00454, PI3_PI4_kinase, 1 hit |
PROSITEi | View protein in PROSITE PS50290, PI3_4_KINASE_3, 1 hit |
i Sequence
Sequence statusi: Complete.
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
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY029199 mRNA Translation: AAK33002.1 |
RefSeqi | NP_446187.1, NM_053735.1 |
Genome annotation databases
Ensembli | ENSRNOT00000019874; ENSRNOP00000019874; ENSRNOG00000014675 |
GeneIDi | 114554 |
KEGGi | rno:114554 |
UCSCi | RGD:620485, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY029199 mRNA Translation: AAK33002.1 |
RefSeqi | NP_446187.1, NM_053735.1 |
3D structure databases
SMRi | Q99M64 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 250373, 1 interactor |
IntActi | Q99M64, 3 interactors |
MINTi | Q99M64 |
STRINGi | 10116.ENSRNOP00000019874 |
PTM databases
iPTMneti | Q99M64 |
PhosphoSitePlusi | Q99M64 |
SwissPalmi | Q99M64 |
Proteomic databases
jPOSTi | Q99M64 |
PaxDbi | Q99M64 |
PRIDEi | Q99M64 |
Genome annotation databases
Ensembli | ENSRNOT00000019874; ENSRNOP00000019874; ENSRNOG00000014675 |
GeneIDi | 114554 |
KEGGi | rno:114554 |
UCSCi | RGD:620485, rat |
Organism-specific databases
CTDi | 55361 |
RGDi | 620485, Pi4k2a |
Phylogenomic databases
eggNOGi | KOG2381, Eukaryota |
GeneTreei | ENSGT00390000010434 |
HOGENOMi | CLU_032516_2_0_1 |
InParanoidi | Q99M64 |
OMAi | CLIPLNG |
OrthoDBi | 1273723at2759 |
PhylomeDBi | Q99M64 |
TreeFami | TF314740 |
Enzyme and pathway databases
Reactomei | R-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
PROi | PR:Q99M64 |
Gene expression databases
Bgeei | ENSRNOG00000014675, Expressed in cerebellum and 20 other tissues |
Genevisiblei | Q99M64, RN |
Family and domain databases
InterProi | View protein in InterPro IPR039756, Lsb6/PI4K2 IPR000403, PI3/4_kinase_cat_dom |
PANTHERi | PTHR12865, PTHR12865, 1 hit |
Pfami | View protein in Pfam PF00454, PI3_PI4_kinase, 1 hit |
PROSITEi | View protein in PROSITE PS50290, PI3_4_KINASE_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | P4K2A_RAT | |
Accessioni | Q99M64Primary (citable) accession number: Q99M64 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 2007 |
Last sequence update: | June 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 129 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families