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Protein

Phosphatidylinositol 4-kinase type 2-alpha

Gene

PI4K2A

Organism
Homo sapiens (Human)
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).Curated6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei152ATP2 Publications1
Binding sitei346ATP2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi131 – 137ATP2 Publications7
Nucleotide bindingi261 – 264ATP2 Publications4

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00573-MONOMER
ReactomeiR-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
SIGNORiQ9BTU6

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4-kinase type 2-alpha (EC:2.7.1.674 Publications)
Alternative name(s):
Phosphatidylinositol 4-kinase type II-alpha
Gene namesi
Name:PI4K2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000155252.13
HGNCiHGNC:30031 PI4K2A
MIMi609763 gene
neXtProtiNX_Q9BTU6

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi129R → E: Reduces enzyme activity, probably due to impaired membrane-association; when associated with E-275 and E-276. 1 Publication1
Mutagenesisi152K → A: Abolishes enzyme activity. 2 Publications1
Mutagenesisi157 – 159EPY → APA: Abolishes enzyme activity. 1 Publication3
Mutagenesisi163N → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi165 – 172KWTKWLQK → AAAAAAAA: Abolishes enzyme activity. 1 Publication8
Mutagenesisi165K → A: Abolishes enzyme activity; when associated with A-168 and A-172. 1 Publication1
Mutagenesisi166W → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi168K → A: Abolishes enzyme activity; when associated with A-165 and A-172. 1 Publication1
Mutagenesisi172K → A: Abolishes enzyme activity; when associated with A-165 and A-168. 1 Publication1
Mutagenesisi174 – 178CCPCC → FFPFF: No effect on membrane-association. 1 Publication5
Mutagenesisi174 – 178CCPCC → SSPSS: Abolishes palmitoylation and impairs membrane-association. 2 Publications5
Mutagenesisi184L → A: Abolishes enzyme activity; when associated with A-349. 1 Publication1
Mutagenesisi263F → A: Abolishes enzyme activity; when associated with A-345. 1 Publication1
Mutagenesisi269D → A: Reduces enzyme activity by half. 1 Publication1
Mutagenesisi275R → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi275R → E: Reduces enzyme activity, probably due to impaired membrane-association; when associated with E-129 and E-276. 1 Publication1
Mutagenesisi276R → E: Reduces enzyme activity, probably due to impaired membrane-association; when associated with E-129 and E-275. 1 Publication1
Mutagenesisi308D → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi345I → A: Abolishes enzyme activity; when associated with A-263. 1 Publication1
Mutagenesisi349L → A: Abolishes enzyme activity; when associated with A-184. 1 Publication1
Mutagenesisi359W → A: Strongly reduced enzyme activity, probably due to impaired membrane-association. Abolishes enzyme activity; when associated with A-365 and A-368. 1 Publication1
Mutagenesisi365Y → A: Reduces enzyme activity, probably due to impaired membrane-association. Abolishes enzyme activity; when associated with A-368 and A-359. 1 Publication1
Mutagenesisi368W → A: Reduces enzyme activity, probably due to impaired membrane-association. Abolishes enzyme activity; when associated with A-359 and A-365. 1 Publication1
Mutagenesisi445Q → A: Reduces enzyme activity. 1 Publication1

Organism-specific databases

DisGeNETi55361
OpenTargetsiENSG00000155252
PharmGKBiPA162399304

Chemistry databases

ChEMBLiCHEMBL2251
GuidetoPHARMACOLOGYi2498

Polymorphism and mutation databases

BioMutaiPI4K2A
DMDMi74752344

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002851581 – 479Phosphatidylinositol 4-kinase type 2-alphaAdd BLAST479

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei5PhosphoserineCombined sources1
Modified residuei9PhosphoserineCombined sources1
Modified residuei44PhosphoserineCombined sources1
Modified residuei47PhosphoserineCombined sources1
Modified residuei51PhosphoserineCombined sources1
Lipidationi174S-palmitoyl cysteine2 Publications1
Lipidationi175S-palmitoyl cysteine2 Publications1
Lipidationi177S-palmitoyl cysteine2 Publications1
Lipidationi178S-palmitoyl cysteine2 Publications1
Modified residuei462PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9BTU6
MaxQBiQ9BTU6
PaxDbiQ9BTU6
PeptideAtlasiQ9BTU6
PRIDEiQ9BTU6
ProteomicsDBi79011

PTM databases

iPTMnetiQ9BTU6
PhosphoSitePlusiQ9BTU6
SwissPalmiQ9BTU6

Expressioni

Tissue specificityi

Widely expressed. Highest expression is observed in kidney, brain, heart, skeletal muscle, and placenta and lowest expression is observed in colon, thymus, and small intestine.1 Publication

Gene expression databases

BgeeiENSG00000155252 Expressed in 212 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_PI4K2A
GenevisibleiQ9BTU6 HS

Organism-specific databases

HPAiCAB030649

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 (PubMed:23146885).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ITCHQ96J025EBI-3239392,EBI-1564678

Protein-protein interaction databases

BioGridi120639, 23 interactors
CORUMiQ9BTU6
IntActiQ9BTU6, 7 interactors
MINTiQ9BTU6
STRINGi9606.ENSP00000359665

Chemistry databases

BindingDBiQ9BTU6

Structurei

Secondary structure

1479
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9BTU6
SMRiQ9BTU6
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 binding1 Publication3
Regioni165 – 178Important for interaction with membranes2 PublicationsAdd BLAST14
Regioni268 – 276Important for interaction with membranes1 Publication9
Regioni359 – 368Important for interaction with membranes1 Publication10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi39 – 42Poly-Ala4
Compositional biasi65 – 97Ala-richAdd BLAST33

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2381 Eukaryota
ENOG410XP06 LUCA
GeneTreeiENSGT00390000010434
HOGENOMiHOG000294076
HOVERGENiHBG059542
InParanoidiQ9BTU6
KOiK13711
OMAiPWNEELR
OrthoDBiEOG091G09F3
PhylomeDBiQ9BTU6
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.

Q9BTU6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDETSPLVSP ERAQPPDYTF PSGSGAHFPQ VPGGAVRVAA AAGSGPSPPG
60 70 80 90 100
SPGHDRERQP LLDRARGAAA QGQTQTVAAQ AQALAAQAAA AAHAAQAHRE
110 120 130 140 150
RNEFPEDPEF EAVVRQAELA IERCIFPERI YQGSSGSYFV KDPQGRIIAV
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 PMDSSSSRDT DWVVVKEPVI KVAAIDNGLA
360 370 380 390 400
FPLKHPDSWR AYPFYWAWLP QAKVPFSQEI KDLILPKISD PNFVKDLEED
410 420 430 440 450
LYELFKKDPG FDRGQFHKQI AVMRGQILNL TQALKDNKSP LHLVQMPPVI
460 470
VETARSHQRS SSESYTQSFQ SRKPFFSWW
Length:479
Mass (Da):54,022
Last modified:June 1, 2001 - v1
Checksum:i9C9F4CE23F197BBD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ303098 mRNA Translation: CAC38065.1
BT007330 mRNA Translation: AAP35994.1
AL355315 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49906.1
CH471066 Genomic DNA Translation: EAW49907.1
BC003167 mRNA Translation: AAH03167.1
AL353952 mRNA Translation: CAB89254.1
CCDSiCCDS7469.1
PIRiT48687
RefSeqiNP_060895.1, NM_018425.3
UniGeneiHs.25300

Genome annotation databases

EnsembliENST00000370631; ENSP00000359665; ENSG00000155252
GeneIDi55361
KEGGihsa:55361
UCSCiuc001kog.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ303098 mRNA Translation: CAC38065.1
BT007330 mRNA Translation: AAP35994.1
AL355315 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49906.1
CH471066 Genomic DNA Translation: EAW49907.1
BC003167 mRNA Translation: AAH03167.1
AL353952 mRNA Translation: CAB89254.1
CCDSiCCDS7469.1
PIRiT48687
RefSeqiNP_060895.1, NM_018425.3
UniGeneiHs.25300

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HNDX-ray3.20A/B78-453[»]
4HNEX-ray2.95A/B78-453[»]
4PLAX-ray2.77A180-468[»]
4YC4X-ray2.58A180-468[»]
5EUTX-ray2.80A179-468[»]
5I0NX-ray2.28A180-468[»]
ProteinModelPortaliQ9BTU6
SMRiQ9BTU6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120639, 23 interactors
CORUMiQ9BTU6
IntActiQ9BTU6, 7 interactors
MINTiQ9BTU6
STRINGi9606.ENSP00000359665

Chemistry databases

BindingDBiQ9BTU6
ChEMBLiCHEMBL2251
GuidetoPHARMACOLOGYi2498

PTM databases

iPTMnetiQ9BTU6
PhosphoSitePlusiQ9BTU6
SwissPalmiQ9BTU6

Polymorphism and mutation databases

BioMutaiPI4K2A
DMDMi74752344

Proteomic databases

EPDiQ9BTU6
MaxQBiQ9BTU6
PaxDbiQ9BTU6
PeptideAtlasiQ9BTU6
PRIDEiQ9BTU6
ProteomicsDBi79011

Protocols and materials databases

DNASUi55361
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370631; ENSP00000359665; ENSG00000155252
GeneIDi55361
KEGGihsa:55361
UCSCiuc001kog.2 human

Organism-specific databases

CTDi55361
DisGeNETi55361
EuPathDBiHostDB:ENSG00000155252.13
GeneCardsiPI4K2A
HGNCiHGNC:30031 PI4K2A
HPAiCAB030649
MIMi609763 gene
neXtProtiNX_Q9BTU6
OpenTargetsiENSG00000155252
PharmGKBiPA162399304
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2381 Eukaryota
ENOG410XP06 LUCA
GeneTreeiENSGT00390000010434
HOGENOMiHOG000294076
HOVERGENiHBG059542
InParanoidiQ9BTU6
KOiK13711
OMAiPWNEELR
OrthoDBiEOG091G09F3
PhylomeDBiQ9BTU6
TreeFamiTF314740

Enzyme and pathway databases

BioCyciMetaCyc:HS00573-MONOMER
ReactomeiR-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
SIGNORiQ9BTU6

Miscellaneous databases

ChiTaRSiPI4K2A human
GeneWikiiPI4K2A
GenomeRNAii55361
PROiPR:Q9BTU6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155252 Expressed in 212 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_PI4K2A
GenevisibleiQ9BTU6 HS

Family and domain databases

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

Entry informationi

Entry nameiP4K2A_HUMAN
AccessioniPrimary (citable) accession number: Q9BTU6
Secondary accession number(s): D3DR59, Q9NSG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: June 1, 2001
Last modified: September 12, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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