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P48426 (PI42A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PIP4K2A
Synonyms:PIP5K2, PIP5K2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length406 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Catalytic activity

ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. Ref.8

Subunit structure

Homodimer By similarity. Interacts with PIP4K2B. Interaction with PIP4K2B may regulate localization to the nucleus. Ref.11

Subcellular location

Cell membrane By similarity. Nucleus. Cytoplasm. 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. Ref.11

Tissue specificity

Expressed ubiquitously, with high levels in the brain. Present in most tissues, except notably skeletal muscle and small intestine. Ref.1 Ref.3

Sequence similarities

Contains 1 PIPK domain.

Caution

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

Biophysicochemical properties

Kinetic parameters:

KM=50 µM for phosphatidylinositol-5- phosphate Ref.11

Vmax=466 pmol/min/µg enzyme

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 406406Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
PRO_0000185465

Regions

Domain33 – 405373PIPK

Amino acid modifications

Modified residue891N6-acetyllysine Ref.10
Modified residue1451N6-acetyllysine Ref.10

Natural variations

Natural variant71L → I.
Corresponds to variant rs11813789 [ dbSNP | Ensembl ].
VAR_059764
Natural variant2511N → S. Ref.3
Corresponds to variant rs10828317 [ dbSNP | Ensembl ].
VAR_024565

Experimental info

Mutagenesis1311G → L: Abolishes catalytic activity; when associated with F-138. Ref.11
Mutagenesis1381Y → F: Abolishes catalytic activity; when associated with L-131. Ref.11
Sequence conflict101 – 1033LRE → CGK in AAB35041. Ref.3
Sequence conflict1091D → V in AAB35041. Ref.3
Sequence conflict1431I → M in AAB35041. Ref.3
Sequence conflict177 – 1782QF → HL in AAB35041. Ref.3
Sequence conflict3331D → E in AAB35041. Ref.3

Secondary structure

..................................................... 406
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P48426 [UniParc].

Last modified August 14, 2001. Version 2.
Checksum: 5BAF0A27CC9EF376

FASTA40646,225
        10         20         30         40         50         60 
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM 

        70         80         90        100        110        120 
LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA 

       130        140        150        160        170        180 
PLPNDSQARS GARFHTSYDK RYIIKTITSE DVAEMHNILK KYHQYIVECH GITLLPQFLG 

       190        200        210        220        230        240 
MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN 

       250        260        270        280        290        300 
EGQKIYIDDN NKKVFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE 

       310        320        330        340        350        360 
EGESDGTHPV GTPPDSPGNT LNSSPPLAPG EFDPNIDVYG IKCHENSPRK EVYFMAIIDI 

       370        380        390        400 
LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF IGHILT 

« Hide

References

« Hide 'large scale' references
[1]"The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases."
Boronenkov I.V., Anderson R.A.
J. Biol. Chem. 270:2881-2884(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-42; 74-88; 93-112; 141-145; 254-259; 281-297 AND 383-406, TISSUE SPECIFICITY.
Tissue: Placenta.
[2]Boronenkov I.V.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 298-310 AND 381-382.
[3]"The cloning and sequence of the C isoform of PtdIns4P 5-kinase."
Divecha N., Truong O., Hsuan J.J., Hinchliffe K.A., Irvine R.F.
Biochem. J. 309:715-719(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT SER-251.
Tissue: Leukocyte.
[4]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Hippocampus.
[8]"A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate."
Rameh L.E., Tolias K.F., Duckworth B.C., Cantley L.C.
Nature 390:192-196(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[9]"Regulation of extranuclear PtdIns5P production by phosphatidylinositol phosphate 4-kinase 2alpha."
Wilcox A., Hinchliffe K.A.
FEBS Lett. 582:1391-1394(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89 AND LYS-145, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha."
Bultsma Y., Keune W.-J., Divecha N.
Biochem. J. 430:223-235(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH PIP4K2B, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-131 AND TYR-138, IDENTIFICATION BY MASS SPECTROMETRY.
[12]"Localization, regulation and function of type II phosphatidylinositol 5-phosphate 4-kinases."
Clarke J.H., Wang M., Irvine R.F.
Adv. Enzyme Regul. 50:12-18(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U14957 mRNA. Translation: AAA64835.2.
S78798 mRNA. Translation: AAB35041.1.
AL513128, AL157707, AL390318 Genomic DNA. Translation: CAH72211.1.
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.
CCDSCCDS7141.1.
PIRA55967.
S57217.
RefSeqNP_005019.2. NM_005028.4.
UniGeneHs.57079.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YBXX-ray2.56A/B35-405[»]
ProteinModelPortalP48426.
SMRP48426. Positions 31-405.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111322. 5 interactions.
IntActP48426. 4 interactions.
MINTMINT-1507380.
STRING9606.ENSP00000365757.

Chemistry

ChEMBLCHEMBL1795194.

PTM databases

PhosphoSiteP48426.

Polymorphism databases

DMDM18266879.

2D gel databases

OGPP48426.

Proteomic databases

MaxQBP48426.
PaxDbP48426.
PeptideAtlasP48426.
PRIDEP48426.

Protocols and materials databases

DNASU5305.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376573; ENSP00000365757; ENSG00000150867.
GeneID5305.
KEGGhsa:5305.
UCSCuc001irl.4. human.

Organism-specific databases

CTD5305.
GeneCardsGC10M022823.
HGNCHGNC:8997. PIP4K2A.
MIM603140. gene.
neXtProtNX_P48426.
Orphanet99860. Precursor B-cell acute lymphoblastic leukemia.
PharmGKBPA162399615.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5253.
HOGENOMHOG000007832.
HOVERGENHBG000072.
InParanoidP48426.
KOK00920.
OMAIVECHGV.
OrthoDBEOG708VZZ.
PhylomeDBP48426.
TreeFamTF354315.

Enzyme and pathway databases

BioCycMetaCyc:HS07693-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP48426.
BgeeP48426.
CleanExHS_PIP4K2A.
GenevestigatorP48426.

Family and domain databases

Gene3D3.30.800.10. 1 hit.
3.30.810.10. 1 hit.
InterProIPR023610. 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.
IPR016034. PInositol-4P-5-kinase_core_sub.
[Graphical view]
PANTHERPTHR23086. PTHR23086. 1 hit.
PfamPF01504. PIP5K. 1 hit.
[Graphical view]
SMARTSM00330. PIPKc. 1 hit.
[Graphical view]
PROSITEPS51455. PIPK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIP4K2A. human.
GeneWikiPIP4K2A.
GenomeRNAi5305.
NextBio20506.
PROP48426.
SOURCESearch...

Entry information

Entry namePI42A_HUMAN
AccessionPrimary (citable) accession number: P48426
Secondary accession number(s): B0YJ66 expand/collapse secondary AC list , D3DRV1, P53807, Q5VUX3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 14, 2001
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM