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Protein

Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha

Gene

PIP4K2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation. May negatively regulate insulin-stimulated glucose uptake by lowering the levels of PtdIns5P. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size.1 Publication

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.1 Publication

Kineticsi

  1. KM=50 µM for phosphatidylinositol-5- phosphate1 Publication
  1. Vmax=466 pmol/min/µg enzyme1 Publication

GO - Molecular functioni

GO - Biological processi

  • megakaryocyte development Source: Ensembl
  • phosphatidylinositol biosynthetic process Source: Reactome
  • positive regulation of autophagosome assembly Source: ParkinsonsUK-UCL
  • regulation of autophagy Source: ParkinsonsUK-UCL
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS07693-MONOMER.
ReactomeiR-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-6811555. PI5P Regulates TP53 Acetylation.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP48426.

Chemistry databases

SwissLipidsiSLP:000000855.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (EC:2.7.1.149)
Alternative name(s):
1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha
Diphosphoinositide kinase 2-alpha
PIP5KIII
Phosphatidylinositol 5-phosphate 4-kinase type II alpha
Short name:
PI(5)P 4-kinase type II alpha
Short name:
PIP4KII-alpha
PtdIns(4)P-5-kinase B isoform
PtdIns(4)P-5-kinase C isoform
PtdIns(5)P-4-kinase isoform 2-alpha
Gene namesi
Name:PIP4K2A
Synonyms:PIP5K2, PIP5K2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:8997. PIP4K2A.

Subcellular locationi

  • Cell membrane By similarity
  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

  • Note: May translocate from the cytosol to the cell membrane upon activation of tyrosine phosphorylation. May translocate from the inner to the outer segments of the rod photoreceptor cells in response to light (By similarity). Localization to the nucleus is modulated by the interaction with PIP4K2B.By similarity

GO - Cellular componenti

  • autophagosome Source: ParkinsonsUK-UCL
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131G → L: Abolishes catalytic activity; when associated with F-138. 1 Publication1
Mutagenesisi138Y → F: Abolishes catalytic activity; when associated with L-131. 1 Publication1

Organism-specific databases

DisGeNETi5305.
MalaCardsiPIP4K2A.
OpenTargetsiENSG00000150867.
Orphaneti99860. Precursor B-cell acute lymphoblastic leukemia.
PharmGKBiPA162399615.

Chemistry databases

ChEMBLiCHEMBL1795194.

Polymorphism and mutation databases

BioMutaiPIP4K2A.
DMDMi18266879.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001854652 – 406Phosphatidylinositol 5-phosphate 4-kinase type-2 alphaAdd BLAST405

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei3PhosphothreonineCombined sources1
Modified residuei14PhosphoserineCombined sources1
Modified residuei89N6-acetyllysineCombined sources1
Modified residuei145N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP48426.
MaxQBiP48426.
PaxDbiP48426.
PeptideAtlasiP48426.
PRIDEiP48426.

2D gel databases

OGPiP48426.

PTM databases

iPTMnetiP48426.
PhosphoSitePlusiP48426.

Expressioni

Tissue specificityi

Expressed ubiquitously, with high levels in the brain. Present in most tissues, except notably skeletal muscle and small intestine.2 Publications

Gene expression databases

BgeeiENSG00000150867.
CleanExiHS_PIP4K2A.
ExpressionAtlasiP48426. baseline and differential.
GenevisibleiP48426. HS.

Organism-specific databases

HPAiHPA068771.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with PIP4K2B. Interaction with PIP4K2B may regulate localization to the nucleus.By similarity1 Publication

Protein-protein interaction databases

BioGridi111322. 102 interactors.
IntActiP48426. 6 interactors.
MINTiMINT-1507380.
STRINGi9606.ENSP00000365757.

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi36 – 52Combined sources17
Helixi63 – 67Combined sources5
Beta strandi69 – 80Combined sources12
Turni81 – 83Combined sources3
Beta strandi86 – 94Combined sources9
Helixi95 – 104Combined sources10
Helixi109 – 117Combined sources9
Beta strandi134 – 136Combined sources3
Beta strandi140 – 147Combined sources8
Helixi149 – 168Combined sources20
Turni169 – 171Combined sources3
Beta strandi178 – 186Combined sources9
Beta strandi189 – 197Combined sources9
Beta strandi202 – 204Combined sources3
Beta strandi207 – 212Combined sources6
Beta strandi215 – 217Combined sources3
Helixi223 – 226Combined sources4
Beta strandi228 – 230Combined sources3
Helixi235 – 240Combined sources6
Helixi249 – 268Combined sources20
Beta strandi271 – 273Combined sources3
Beta strandi275 – 282Combined sources8
Helixi283 – 291Combined sources9
Turni334 – 336Combined sources3
Beta strandi340 – 342Combined sources3
Beta strandi351 – 358Combined sources8
Beta strandi362 – 364Combined sources3
Helixi390 – 404Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YBXX-ray2.56A/B35-405[»]
ProteinModelPortaliP48426.
SMRiP48426.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 405PIPKPROSITE-ProRule annotationAdd BLAST373

Sequence similaritiesi

Contains 1 PIPK domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0229. Eukaryota.
COG5253. LUCA.
GeneTreeiENSGT00760000119184.
HOGENOMiHOG000007832.
HOVERGENiHBG000072.
InParanoidiP48426.
KOiK00920.
OMAiIVECHGV.
OrthoDBiEOG091G0857.
PhylomeDBiP48426.
TreeFamiTF354315.

Family and domain databases

Gene3Di3.30.800.10. 1 hit.
3.30.810.10. 1 hit.
InterProiIPR023610. PInositol-4-P-5-kinase.
IPR027483. PInositol-4-P-5-kinase_C.
IPR002498. PInositol-4-P-5-kinase_core.
IPR027484. PInositol-4-P-5-kinase_N.
[Graphical view]
PANTHERiPTHR23086. PTHR23086. 1 hit.
PfamiPF01504. PIP5K. 1 hit.
[Graphical view]
SMARTiSM00330. PIPKc. 1 hit.
[Graphical view]
PROSITEiPS51455. PIPK. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48426-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN
60 70 80 90 100
ELSHVQIPVM LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN
110 120 130 140 150
LRERFGIDDQ DFQNSLTRSA PLPNDSQARS GARFHTSYDK RYIIKTITSE
160 170 180 190 200
DVAEMHNILK KYHQYIVECH GITLLPQFLG MYRLNVDGVE IYVIVTRNVF
210 220 230 240 250
SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN EGQKIYIDDN
260 270 280 290 300
NKKVFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE
310 320 330 340 350
EGESDGTHPV GTPPDSPGNT LNSSPPLAPG EFDPNIDVYG IKCHENSPRK
360 370 380 390 400
EVYFMAIIDI LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF

IGHILT
Length:406
Mass (Da):46,225
Last modified:August 14, 2001 - v2
Checksum:i5BAF0A27CC9EF376
GO
Isoform 2 (identifier: P48426-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Note: No experimental confirmation available.
Show »
Length:347
Mass (Da):39,802
Checksum:iE8E3F2DADE991A74
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti101 – 103LRE → CGK in AAB35041 (PubMed:7639683).Curated3
Sequence conflicti109D → V in AAB35041 (PubMed:7639683).Curated1
Sequence conflicti143I → M in AAB35041 (PubMed:7639683).Curated1
Sequence conflicti177 – 178QF → HL in AAB35041 (PubMed:7639683).Curated2
Sequence conflicti333D → E in AAB35041 (PubMed:7639683).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0597647L → I.Corresponds to variant rs11813789dbSNPEnsembl.1
Natural variantiVAR_024565251N → S.1 PublicationCorresponds to variant rs10828317dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564581 – 59Missing in isoform 2. 1 PublicationAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14957 mRNA. Translation: AAA64835.2.
S78798 mRNA. Translation: AAB35041.1.
AL513128, AL157707, AL390318 Genomic DNA. Translation: CAH72211.1.
AK294817 mRNA. Translation: BAG57933.1.
EF445009 Genomic DNA. Translation: ACA06044.1.
EF445009 Genomic DNA. Translation: ACA06045.1.
AL157707, AL390318, AL513128 Genomic DNA. Translation: CAI39585.1.
AL390318, AL157707, AL513128 Genomic DNA. Translation: CAH70526.1.
CH471072 Genomic DNA. Translation: EAW86140.1.
CH471072 Genomic DNA. Translation: EAW86141.1.
BC018034 mRNA. Translation: AAH18034.1.
CCDSiCCDS7141.1. [P48426-1]
CCDS81443.1. [P48426-2]
PIRiA55967.
S57217.
RefSeqiNP_001316991.1. NM_001330062.1.
NP_005019.2. NM_005028.4. [P48426-1]
XP_016871819.1. XM_017016330.1. [P48426-2]
XP_016871820.1. XM_017016331.1. [P48426-2]
UniGeneiHs.57079.

Genome annotation databases

EnsembliENST00000376573; ENSP00000365757; ENSG00000150867. [P48426-1]
ENST00000545335; ENSP00000442098; ENSG00000150867. [P48426-2]
GeneIDi5305.
KEGGihsa:5305.
UCSCiuc001irl.5. human. [P48426-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14957 mRNA. Translation: AAA64835.2.
S78798 mRNA. Translation: AAB35041.1.
AL513128, AL157707, AL390318 Genomic DNA. Translation: CAH72211.1.
AK294817 mRNA. Translation: BAG57933.1.
EF445009 Genomic DNA. Translation: ACA06044.1.
EF445009 Genomic DNA. Translation: ACA06045.1.
AL157707, AL390318, AL513128 Genomic DNA. Translation: CAI39585.1.
AL390318, AL157707, AL513128 Genomic DNA. Translation: CAH70526.1.
CH471072 Genomic DNA. Translation: EAW86140.1.
CH471072 Genomic DNA. Translation: EAW86141.1.
BC018034 mRNA. Translation: AAH18034.1.
CCDSiCCDS7141.1. [P48426-1]
CCDS81443.1. [P48426-2]
PIRiA55967.
S57217.
RefSeqiNP_001316991.1. NM_001330062.1.
NP_005019.2. NM_005028.4. [P48426-1]
XP_016871819.1. XM_017016330.1. [P48426-2]
XP_016871820.1. XM_017016331.1. [P48426-2]
UniGeneiHs.57079.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YBXX-ray2.56A/B35-405[»]
ProteinModelPortaliP48426.
SMRiP48426.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111322. 102 interactors.
IntActiP48426. 6 interactors.
MINTiMINT-1507380.
STRINGi9606.ENSP00000365757.

Chemistry databases

ChEMBLiCHEMBL1795194.
SwissLipidsiSLP:000000855.

PTM databases

iPTMnetiP48426.
PhosphoSitePlusiP48426.

Polymorphism and mutation databases

BioMutaiPIP4K2A.
DMDMi18266879.

2D gel databases

OGPiP48426.

Proteomic databases

EPDiP48426.
MaxQBiP48426.
PaxDbiP48426.
PeptideAtlasiP48426.
PRIDEiP48426.

Protocols and materials databases

DNASUi5305.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376573; ENSP00000365757; ENSG00000150867. [P48426-1]
ENST00000545335; ENSP00000442098; ENSG00000150867. [P48426-2]
GeneIDi5305.
KEGGihsa:5305.
UCSCiuc001irl.5. human. [P48426-1]

Organism-specific databases

CTDi5305.
DisGeNETi5305.
GeneCardsiPIP4K2A.
HGNCiHGNC:8997. PIP4K2A.
HPAiHPA068771.
MalaCardsiPIP4K2A.
MIMi603140. gene.
neXtProtiNX_P48426.
OpenTargetsiENSG00000150867.
Orphaneti99860. Precursor B-cell acute lymphoblastic leukemia.
PharmGKBiPA162399615.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0229. Eukaryota.
COG5253. LUCA.
GeneTreeiENSGT00760000119184.
HOGENOMiHOG000007832.
HOVERGENiHBG000072.
InParanoidiP48426.
KOiK00920.
OMAiIVECHGV.
OrthoDBiEOG091G0857.
PhylomeDBiP48426.
TreeFamiTF354315.

Enzyme and pathway databases

BioCyciMetaCyc:HS07693-MONOMER.
ReactomeiR-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-6811555. PI5P Regulates TP53 Acetylation.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP48426.

Miscellaneous databases

ChiTaRSiPIP4K2A. human.
GeneWikiiPIP4K2A.
GenomeRNAii5305.
PROiP48426.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150867.
CleanExiHS_PIP4K2A.
ExpressionAtlasiP48426. baseline and differential.
GenevisibleiP48426. HS.

Family and domain databases

Gene3Di3.30.800.10. 1 hit.
3.30.810.10. 1 hit.
InterProiIPR023610. PInositol-4-P-5-kinase.
IPR027483. PInositol-4-P-5-kinase_C.
IPR002498. PInositol-4-P-5-kinase_core.
IPR027484. PInositol-4-P-5-kinase_N.
[Graphical view]
PANTHERiPTHR23086. PTHR23086. 1 hit.
PfamiPF01504. PIP5K. 1 hit.
[Graphical view]
SMARTiSM00330. PIPKc. 1 hit.
[Graphical view]
PROSITEiPS51455. PIPK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPI42A_HUMAN
AccessioniPrimary (citable) accession number: P48426
Secondary accession number(s): B0YJ66
, B4DGX2, D3DRV1, P53807, Q5VUX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 14, 2001
Last modified: November 30, 2016
This is version 146 of the entry and version 2 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

Caution

This protein was previously thought to be a phosphatidylinositol 4-phosphate 5-kinase.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.