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Protein

Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha

Gene

PIP4K2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

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
  • phospholipid metabolic 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

Keywordsi

Molecular functionKinase, Transferase
LigandATP-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
R-HSA-8847453 Synthesis of PIPs in the nucleus
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

EuPathDBiHostDB:ENSG00000150867.13
HGNCiHGNC:8997 PIP4K2A
MIMi603140 gene
neXtProtiNX_P48426

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 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

HPAiHPA065440
HPA068771

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, 106 interactors
IntActiP48426, 7 interactors
MINTiP48426
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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.800.10, 1 hit
3.30.810.10, 1 hit
InterProiView protein in InterPro
IPR023610 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
PANTHERiPTHR23086 PTHR23086, 1 hit
PfamiView protein in Pfam
PF01504 PIP5K, 1 hit
SMARTiView protein in SMART
SM00330 PIPKc, 1 hit
PROSITEiView protein in PROSITE
PS51455 PIPK, 1 hit

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 dbSNP:rs11813789Ensembl.1
Natural variantiVAR_024565251N → S1 PublicationCorresponds to variant dbSNP:rs2230469Ensembl.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 [P48426-2]
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

Similar proteinsi

Entry informationi

Entry nameiPI42A_HUMAN
AccessioniPrimary (citable) accession number: P48426
Secondary accession number(s): B0YJ66
, B4DGX2, D3DRV1, P53807, Q5VUX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 14, 2001
Last modified: May 23, 2018
This is version 159 of the entry and version 2 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, 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

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