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Protein

Phosphatidylinositol 4-kinase type 2-alpha

Gene

PI4K2A

Organism
Homo sapiens (Human)
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).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

  • basophil degranulation Source: Ensembl
  • phosphatidylinositol biosynthetic process Source: UniProtKB
  • phosphatidylinositol phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00573-MONOMER.
ZFISH: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

HGNCiHGNC:30031. PI4K2A.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasmic vesicle Source: UniProtKB
  • cytosol Source: Reactome
  • 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: UniProtKB
  • membrane Source: UniProtKB
  • membrane raft Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perikaryon Source: Ensembl
  • presynaptic membrane Source: UniProtKB
  • protein complex Source: Ensembl
  • 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

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.

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.
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

GO - Molecular functioni

  • AP-3 adaptor complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120639. 22 interactors.
IntActiQ9BTU6. 7 interactors.
STRINGi9606.ENSP00000359665.

Chemistry databases

BindingDBiQ9BTU6.

Structurei

Secondary structure

1479
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi78 – 93Combined sources16
Helixi95 – 99Combined sources5
Helixi108 – 122Combined sources15
Beta strandi131 – 133Combined sources3
Beta strandi138 – 141Combined sources4
Beta strandi147 – 153Combined sources7
Helixi154 – 156Combined sources3
Helixi167 – 171Combined sources5
Helixi189 – 203Combined sources15
Beta strandi211 – 216Combined sources6
Helixi225 – 231Combined sources7
Beta strandi235 – 237Combined sources3
Beta strandi249 – 251Combined sources3
Beta strandi256 – 262Combined sources7
Beta strandi266 – 269Combined sources4
Helixi270 – 279Combined sources10
Helixi284 – 304Combined sources21
Beta strandi313 – 318Combined sources6
Beta strandi339 – 344Combined sources6
Turni359 – 361Combined sources3
Helixi365 – 368Combined sources4
Helixi370 – 373Combined sources4
Helixi378 – 388Combined sources11
Helixi391 – 405Combined sources15
Helixi413 – 435Combined sources23
Helixi440 – 444Combined sources5

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-ray2.77A76-172[»]
A180-468[»]
4YC4X-ray2.58A76-172[»]
A180-468[»]
5EUTX-ray2.80A76-172[»]
A179-468[»]
5I0NX-ray2.28A180-468[»]
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

Contains 1 PI3K/PI4K domain.Curated

Phylogenomic databases

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

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. Translation: CAI15460.1.
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.

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. Translation: CAI15460.1.
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-ray2.77A76-172[»]
A180-468[»]
4YC4X-ray2.58A76-172[»]
A180-468[»]
5EUTX-ray2.80A76-172[»]
A179-468[»]
5I0NX-ray2.28A180-468[»]
ProteinModelPortaliQ9BTU6.
SMRiQ9BTU6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120639. 22 interactors.
IntActiQ9BTU6. 7 interactors.
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.

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.
GeneCardsiPI4K2A.
HGNCiHGNC:30031. PI4K2A.
HPAiCAB030649.
MIMi609763. gene.
neXtProtiNX_Q9BTU6.
OpenTargetsiENSG00000155252.
PharmGKBiPA162399304.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciMetaCyc:HS00573-MONOMER.
ZFISH: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.
PROiQ9BTU6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155252.
CleanExiHS_PI4K2A.
GenevisibleiQ9BTU6. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q9BTU6
Secondary accession number(s): D3DR59, Q9NSG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 130 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.