Full text data of PIP4K2A
PIP4K2A
(PIP5K2, PIP5K2A)
[Confidence: high (present in two of the MS resources)]
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha; 2.7.1.149 (1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha; Diphosphoinositide kinase 2-alpha; PIP5KIII; Phosphatidylinositol 5-phosphate 4-kinase type II alpha; PI(5)P 4-kinase type II alpha; PIP4KII-alpha; PtdIns(4)P-5-kinase B isoform; PtdIns(4)P-5-kinase C isoform; PtdIns(5)P-4-kinase isoform 2-alpha)
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha; 2.7.1.149 (1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha; Diphosphoinositide kinase 2-alpha; PIP5KIII; Phosphatidylinositol 5-phosphate 4-kinase type II alpha; PI(5)P 4-kinase type II alpha; PIP4KII-alpha; PtdIns(4)P-5-kinase B isoform; PtdIns(4)P-5-kinase C isoform; PtdIns(5)P-4-kinase isoform 2-alpha)
hRBCD
IPI00009688
IPI00009688 Phosphatidylinositol-4-phosphate 5-kinase type II alpha Phosphatidylinositol-4-phosphate 5-kinase type II alpha membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 integral to membrane n/a found at its expected molecular weight found at molecular weight
IPI00009688 Phosphatidylinositol-4-phosphate 5-kinase type II alpha Phosphatidylinositol-4-phosphate 5-kinase type II alpha membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 integral to membrane n/a found at its expected molecular weight found at molecular weight
UniProt
P48426
ID PI42A_HUMAN Reviewed; 406 AA.
AC P48426; B0YJ66; D3DRV1; P53807; Q5VUX3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-AUG-2001, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha;
DE EC=2.7.1.149;
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha;
DE AltName: Full=Diphosphoinositide kinase 2-alpha;
DE AltName: Full=PIP5KIII;
DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II alpha;
DE Short=PI(5)P 4-kinase type II alpha;
DE Short=PIP4KII-alpha;
DE AltName: Full=PtdIns(4)P-5-kinase B isoform;
DE AltName: Full=PtdIns(4)P-5-kinase C isoform;
DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-alpha;
GN Name=PIP4K2A; Synonyms=PIP5K2, PIP5K2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-42; 74-88; 93-112;
RP 141-145; 254-259; 281-297 AND 383-406, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=7852364; DOI=10.1074/jbc.270.7.2881;
RA Boronenkov I.V., Anderson R.A.;
RT "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a
RT novel family of lipid kinases.";
RL J. Biol. Chem. 270:2881-2884(1995).
RN [2]
RP SEQUENCE REVISION TO 298-310 AND 381-382.
RA Boronenkov I.V.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-251.
RC TISSUE=Leukocyte;
RX PubMed=7639683;
RA Divecha N., Truong O., Hsuan J.J., Hinchliffe K.A., Irvine R.F.;
RT "The cloning and sequence of the C isoform of PtdIns4P 5-kinase.";
RL Biochem. J. 309:715-719(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CATALYTIC ACTIVITY.
RX PubMed=9367159; DOI=10.1038/36621;
RA Rameh L.E., Tolias K.F., Duckworth B.C., Cantley L.C.;
RT "A new pathway for synthesis of phosphatidylinositol-4,5-
RT bisphosphate.";
RL Nature 390:192-196(1997).
RN [9]
RP FUNCTION.
RX PubMed=18364242; DOI=10.1016/j.febslet.2008.03.022;
RA Wilcox A., Hinchliffe K.A.;
RT "Regulation of extranuclear PtdIns5P production by
RT phosphatidylinositol phosphate 4-kinase 2alpha.";
RL FEBS Lett. 582:1391-1394(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-3 AND SER-14, MASS SPECTROMETRY, AND CLEAVAGE
RP OF INITIATOR METHIONINE.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89 AND LYS-145, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH PIP4K2B, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF GLY-131 AND TYR-138, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=20583997; DOI=10.1042/BJ20100341;
RA Bultsma Y., Keune W.-J., Divecha N.;
RT "PIP4Kbeta interacts with and modulates nuclear localization of the
RT high-activity PtdIns5P-4-kinase isoform PIP4Kalpha.";
RL Biochem. J. 430:223-235(2010).
RN [15]
RP REVIEW ON FUNCTION.
RX PubMed=19896968; DOI=10.1016/j.advenzreg.2009.10.006;
RA Clarke J.H., Wang M., Irvine R.F.;
RT "Localization, regulation and function of type II phosphatidylinositol
RT 5-phosphate 4-kinases.";
RL Adv. Enzyme Regul. 50:12-18(2010).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-14, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 5-
CC phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol
CC ring, to form phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2). May exert its function by regulating the levels
CC of PtdIns5P, which functions in the cytosol by increasing AKT
CC activity and in the nucleus signals through ING2. May regulate the
CC pool of cytosolic PtdIns5P in response to the activation of
CC tyrosine phosphorylation. May negatively regulate insulin-
CC stimulated glucose uptake by lowering the levels of PtdIns5P. May
CC be involved in thrombopoiesis, and the terminal maturation of
CC megakaryocytes and regulation of their size.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 5-
CC phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for phosphatidylinositol-5- phosphate;
CC Vmax=466 pmol/min/ug enzyme;
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with PIP4K2B.
CC Interaction with PIP4K2B may regulate localization to the nucleus.
CC -!- SUBCELLULAR LOCATION: Cell membrane (By similarity). Nucleus.
CC Cytoplasm. Note=May translocate from the cytosol to the cell
CC membrane upon activation of tyrosine phosphorylation. May
CC translocate from the inner to the outer segments of the rod
CC photoreceptor cells in response to light (By similarity).
CC Localization to the nucleus is modulated by the interaction with
CC PIP4K2B.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously, with high levels in
CC the brain. Present in most tissues, except notably skeletal muscle
CC and small intestine.
CC -!- SIMILARITY: Contains 1 PIPK domain.
CC -!- CAUTION: This protein was previously thought to be a
CC phosphatidylinositol 4-phosphate 5-kinase.
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DR EMBL; U14957; AAA64835.2; -; mRNA.
DR EMBL; S78798; AAB35041.1; -; mRNA.
DR EMBL; AL513128; CAH72211.1; -; Genomic_DNA.
DR EMBL; AL157707; CAH72211.1; JOINED; Genomic_DNA.
DR EMBL; AL390318; CAH72211.1; JOINED; Genomic_DNA.
DR EMBL; EF445009; ACA06044.1; -; Genomic_DNA.
DR EMBL; EF445009; ACA06045.1; -; Genomic_DNA.
DR EMBL; AL157707; CAI39585.1; -; Genomic_DNA.
DR EMBL; AL390318; CAI39585.1; JOINED; Genomic_DNA.
DR EMBL; AL513128; CAI39585.1; JOINED; Genomic_DNA.
DR EMBL; AL390318; CAH70526.1; -; Genomic_DNA.
DR EMBL; AL157707; CAH70526.1; JOINED; Genomic_DNA.
DR EMBL; AL513128; CAH70526.1; JOINED; Genomic_DNA.
DR EMBL; CH471072; EAW86140.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86141.1; -; Genomic_DNA.
DR EMBL; BC018034; AAH18034.1; -; mRNA.
DR PIR; A55967; A55967.
DR PIR; S57217; S57217.
DR RefSeq; NP_005019.2; NM_005028.4.
DR UniGene; Hs.57079; -.
DR PDB; 2YBX; X-ray; 2.56 A; A/B=35-405.
DR PDBsum; 2YBX; -.
DR ProteinModelPortal; P48426; -.
DR SMR; P48426; 31-405.
DR IntAct; P48426; 3.
DR MINT; MINT-1507380; -.
DR STRING; 9606.ENSP00000365757; -.
DR ChEMBL; CHEMBL1795194; -.
DR PhosphoSite; P48426; -.
DR DMDM; 18266879; -.
DR OGP; P48426; -.
DR PaxDb; P48426; -.
DR PeptideAtlas; P48426; -.
DR PRIDE; P48426; -.
DR DNASU; 5305; -.
DR Ensembl; ENST00000376573; ENSP00000365757; ENSG00000150867.
DR GeneID; 5305; -.
DR KEGG; hsa:5305; -.
DR UCSC; uc001irl.4; human.
DR CTD; 5305; -.
DR GeneCards; GC10M022823; -.
DR HGNC; HGNC:8997; PIP4K2A.
DR MIM; 603140; gene.
DR neXtProt; NX_P48426; -.
DR PharmGKB; PA162399615; -.
DR eggNOG; COG5253; -.
DR HOGENOM; HOG000007832; -.
DR HOVERGEN; HBG000072; -.
DR InParanoid; P48426; -.
DR KO; K00920; -.
DR OMA; IVECHGV; -.
DR OrthoDB; EOG708VZZ; -.
DR PhylomeDB; P48426; -.
DR BioCyc; MetaCyc:HS07693-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PIP4K2A; human.
DR GeneWiki; PIP4K2A; -.
DR GenomeRNAi; 5305; -.
DR NextBio; 20506; -.
DR PRO; PR:P48426; -.
DR ArrayExpress; P48426; -.
DR Bgee; P48426; -.
DR CleanEx; HS_PIP4K2A; -.
DR Genevestigator; P48426; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; NAS:UniProtKB.
DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.30.800.10; -; 1.
DR Gene3D; 3.30.810.10; -; 1.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR027483; PInositol-4-P-5-kinase_C.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR InterPro; IPR016034; PInositol-4P-5-kinase_core_sub.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell membrane;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Kinase;
KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 406 Phosphatidylinositol 5-phosphate 4-kinase
FT type-2 alpha.
FT /FTId=PRO_0000185465.
FT DOMAIN 33 405 PIPK.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 3 3 Phosphothreonine.
FT MOD_RES 14 14 Phosphoserine.
FT MOD_RES 89 89 N6-acetyllysine.
FT MOD_RES 145 145 N6-acetyllysine.
FT VARIANT 7 7 L -> I (in dbSNP:rs11813789).
FT /FTId=VAR_059764.
FT VARIANT 251 251 N -> S (in dbSNP:rs10828317).
FT /FTId=VAR_024565.
FT MUTAGEN 131 131 G->L: Abolishes catalytic activity; when
FT associated with F-138.
FT MUTAGEN 138 138 Y->F: Abolishes catalytic activity; when
FT associated with L-131.
FT CONFLICT 101 103 LRE -> CGK (in Ref. 3; AAB35041).
FT CONFLICT 109 109 D -> V (in Ref. 3; AAB35041).
FT CONFLICT 143 143 I -> M (in Ref. 3; AAB35041).
FT CONFLICT 177 178 QF -> HL (in Ref. 3; AAB35041).
FT CONFLICT 333 333 D -> E (in Ref. 3; AAB35041).
FT HELIX 36 52
FT HELIX 63 67
FT STRAND 69 80
FT TURN 81 83
FT STRAND 86 94
FT HELIX 95 104
FT HELIX 109 117
FT STRAND 134 136
FT STRAND 140 147
FT HELIX 149 168
FT TURN 169 171
FT STRAND 178 186
FT STRAND 189 197
FT STRAND 202 204
FT STRAND 207 212
FT STRAND 215 217
FT HELIX 223 226
FT STRAND 228 230
FT HELIX 235 240
FT HELIX 249 268
FT STRAND 271 273
FT STRAND 275 282
FT HELIX 283 291
FT TURN 334 336
FT STRAND 340 342
FT STRAND 351 358
FT STRAND 362 364
FT HELIX 390 404
SQ SEQUENCE 406 AA; 46225 MW; 5BAF0A27CC9EF376 CRC64;
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM
LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA
PLPNDSQARS GARFHTSYDK RYIIKTITSE DVAEMHNILK KYHQYIVECH GITLLPQFLG
MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN
EGQKIYIDDN NKKVFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE
EGESDGTHPV GTPPDSPGNT LNSSPPLAPG EFDPNIDVYG IKCHENSPRK EVYFMAIIDI
LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF IGHILT
//
ID PI42A_HUMAN Reviewed; 406 AA.
AC P48426; B0YJ66; D3DRV1; P53807; Q5VUX3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-AUG-2001, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha;
DE EC=2.7.1.149;
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha;
DE AltName: Full=Diphosphoinositide kinase 2-alpha;
DE AltName: Full=PIP5KIII;
DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II alpha;
DE Short=PI(5)P 4-kinase type II alpha;
DE Short=PIP4KII-alpha;
DE AltName: Full=PtdIns(4)P-5-kinase B isoform;
DE AltName: Full=PtdIns(4)P-5-kinase C isoform;
DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-alpha;
GN Name=PIP4K2A; Synonyms=PIP5K2, PIP5K2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-42; 74-88; 93-112;
RP 141-145; 254-259; 281-297 AND 383-406, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=7852364; DOI=10.1074/jbc.270.7.2881;
RA Boronenkov I.V., Anderson R.A.;
RT "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a
RT novel family of lipid kinases.";
RL J. Biol. Chem. 270:2881-2884(1995).
RN [2]
RP SEQUENCE REVISION TO 298-310 AND 381-382.
RA Boronenkov I.V.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-251.
RC TISSUE=Leukocyte;
RX PubMed=7639683;
RA Divecha N., Truong O., Hsuan J.J., Hinchliffe K.A., Irvine R.F.;
RT "The cloning and sequence of the C isoform of PtdIns4P 5-kinase.";
RL Biochem. J. 309:715-719(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CATALYTIC ACTIVITY.
RX PubMed=9367159; DOI=10.1038/36621;
RA Rameh L.E., Tolias K.F., Duckworth B.C., Cantley L.C.;
RT "A new pathway for synthesis of phosphatidylinositol-4,5-
RT bisphosphate.";
RL Nature 390:192-196(1997).
RN [9]
RP FUNCTION.
RX PubMed=18364242; DOI=10.1016/j.febslet.2008.03.022;
RA Wilcox A., Hinchliffe K.A.;
RT "Regulation of extranuclear PtdIns5P production by
RT phosphatidylinositol phosphate 4-kinase 2alpha.";
RL FEBS Lett. 582:1391-1394(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-3 AND SER-14, MASS SPECTROMETRY, AND CLEAVAGE
RP OF INITIATOR METHIONINE.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89 AND LYS-145, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH PIP4K2B, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF GLY-131 AND TYR-138, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=20583997; DOI=10.1042/BJ20100341;
RA Bultsma Y., Keune W.-J., Divecha N.;
RT "PIP4Kbeta interacts with and modulates nuclear localization of the
RT high-activity PtdIns5P-4-kinase isoform PIP4Kalpha.";
RL Biochem. J. 430:223-235(2010).
RN [15]
RP REVIEW ON FUNCTION.
RX PubMed=19896968; DOI=10.1016/j.advenzreg.2009.10.006;
RA Clarke J.H., Wang M., Irvine R.F.;
RT "Localization, regulation and function of type II phosphatidylinositol
RT 5-phosphate 4-kinases.";
RL Adv. Enzyme Regul. 50:12-18(2010).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-14, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 5-
CC phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol
CC ring, to form phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2). May exert its function by regulating the levels
CC of PtdIns5P, which functions in the cytosol by increasing AKT
CC activity and in the nucleus signals through ING2. May regulate the
CC pool of cytosolic PtdIns5P in response to the activation of
CC tyrosine phosphorylation. May negatively regulate insulin-
CC stimulated glucose uptake by lowering the levels of PtdIns5P. May
CC be involved in thrombopoiesis, and the terminal maturation of
CC megakaryocytes and regulation of their size.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 5-
CC phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for phosphatidylinositol-5- phosphate;
CC Vmax=466 pmol/min/ug enzyme;
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with PIP4K2B.
CC Interaction with PIP4K2B may regulate localization to the nucleus.
CC -!- SUBCELLULAR LOCATION: Cell membrane (By similarity). Nucleus.
CC Cytoplasm. Note=May translocate from the cytosol to the cell
CC membrane upon activation of tyrosine phosphorylation. May
CC translocate from the inner to the outer segments of the rod
CC photoreceptor cells in response to light (By similarity).
CC Localization to the nucleus is modulated by the interaction with
CC PIP4K2B.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously, with high levels in
CC the brain. Present in most tissues, except notably skeletal muscle
CC and small intestine.
CC -!- SIMILARITY: Contains 1 PIPK domain.
CC -!- CAUTION: This protein was previously thought to be a
CC phosphatidylinositol 4-phosphate 5-kinase.
CC -----------------------------------------------------------------------
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DR EMBL; U14957; AAA64835.2; -; mRNA.
DR EMBL; S78798; AAB35041.1; -; mRNA.
DR EMBL; AL513128; CAH72211.1; -; Genomic_DNA.
DR EMBL; AL157707; CAH72211.1; JOINED; Genomic_DNA.
DR EMBL; AL390318; CAH72211.1; JOINED; Genomic_DNA.
DR EMBL; EF445009; ACA06044.1; -; Genomic_DNA.
DR EMBL; EF445009; ACA06045.1; -; Genomic_DNA.
DR EMBL; AL157707; CAI39585.1; -; Genomic_DNA.
DR EMBL; AL390318; CAI39585.1; JOINED; Genomic_DNA.
DR EMBL; AL513128; CAI39585.1; JOINED; Genomic_DNA.
DR EMBL; AL390318; CAH70526.1; -; Genomic_DNA.
DR EMBL; AL157707; CAH70526.1; JOINED; Genomic_DNA.
DR EMBL; AL513128; CAH70526.1; JOINED; Genomic_DNA.
DR EMBL; CH471072; EAW86140.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86141.1; -; Genomic_DNA.
DR EMBL; BC018034; AAH18034.1; -; mRNA.
DR PIR; A55967; A55967.
DR PIR; S57217; S57217.
DR RefSeq; NP_005019.2; NM_005028.4.
DR UniGene; Hs.57079; -.
DR PDB; 2YBX; X-ray; 2.56 A; A/B=35-405.
DR PDBsum; 2YBX; -.
DR ProteinModelPortal; P48426; -.
DR SMR; P48426; 31-405.
DR IntAct; P48426; 3.
DR MINT; MINT-1507380; -.
DR STRING; 9606.ENSP00000365757; -.
DR ChEMBL; CHEMBL1795194; -.
DR PhosphoSite; P48426; -.
DR DMDM; 18266879; -.
DR OGP; P48426; -.
DR PaxDb; P48426; -.
DR PeptideAtlas; P48426; -.
DR PRIDE; P48426; -.
DR DNASU; 5305; -.
DR Ensembl; ENST00000376573; ENSP00000365757; ENSG00000150867.
DR GeneID; 5305; -.
DR KEGG; hsa:5305; -.
DR UCSC; uc001irl.4; human.
DR CTD; 5305; -.
DR GeneCards; GC10M022823; -.
DR HGNC; HGNC:8997; PIP4K2A.
DR MIM; 603140; gene.
DR neXtProt; NX_P48426; -.
DR PharmGKB; PA162399615; -.
DR eggNOG; COG5253; -.
DR HOGENOM; HOG000007832; -.
DR HOVERGEN; HBG000072; -.
DR InParanoid; P48426; -.
DR KO; K00920; -.
DR OMA; IVECHGV; -.
DR OrthoDB; EOG708VZZ; -.
DR PhylomeDB; P48426; -.
DR BioCyc; MetaCyc:HS07693-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PIP4K2A; human.
DR GeneWiki; PIP4K2A; -.
DR GenomeRNAi; 5305; -.
DR NextBio; 20506; -.
DR PRO; PR:P48426; -.
DR ArrayExpress; P48426; -.
DR Bgee; P48426; -.
DR CleanEx; HS_PIP4K2A; -.
DR Genevestigator; P48426; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; NAS:UniProtKB.
DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.30.800.10; -; 1.
DR Gene3D; 3.30.810.10; -; 1.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR027483; PInositol-4-P-5-kinase_C.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR InterPro; IPR016034; PInositol-4P-5-kinase_core_sub.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell membrane;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Kinase;
KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 406 Phosphatidylinositol 5-phosphate 4-kinase
FT type-2 alpha.
FT /FTId=PRO_0000185465.
FT DOMAIN 33 405 PIPK.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 3 3 Phosphothreonine.
FT MOD_RES 14 14 Phosphoserine.
FT MOD_RES 89 89 N6-acetyllysine.
FT MOD_RES 145 145 N6-acetyllysine.
FT VARIANT 7 7 L -> I (in dbSNP:rs11813789).
FT /FTId=VAR_059764.
FT VARIANT 251 251 N -> S (in dbSNP:rs10828317).
FT /FTId=VAR_024565.
FT MUTAGEN 131 131 G->L: Abolishes catalytic activity; when
FT associated with F-138.
FT MUTAGEN 138 138 Y->F: Abolishes catalytic activity; when
FT associated with L-131.
FT CONFLICT 101 103 LRE -> CGK (in Ref. 3; AAB35041).
FT CONFLICT 109 109 D -> V (in Ref. 3; AAB35041).
FT CONFLICT 143 143 I -> M (in Ref. 3; AAB35041).
FT CONFLICT 177 178 QF -> HL (in Ref. 3; AAB35041).
FT CONFLICT 333 333 D -> E (in Ref. 3; AAB35041).
FT HELIX 36 52
FT HELIX 63 67
FT STRAND 69 80
FT TURN 81 83
FT STRAND 86 94
FT HELIX 95 104
FT HELIX 109 117
FT STRAND 134 136
FT STRAND 140 147
FT HELIX 149 168
FT TURN 169 171
FT STRAND 178 186
FT STRAND 189 197
FT STRAND 202 204
FT STRAND 207 212
FT STRAND 215 217
FT HELIX 223 226
FT STRAND 228 230
FT HELIX 235 240
FT HELIX 249 268
FT STRAND 271 273
FT STRAND 275 282
FT HELIX 283 291
FT TURN 334 336
FT STRAND 340 342
FT STRAND 351 358
FT STRAND 362 364
FT HELIX 390 404
SQ SEQUENCE 406 AA; 46225 MW; 5BAF0A27CC9EF376 CRC64;
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM
LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA
PLPNDSQARS GARFHTSYDK RYIIKTITSE DVAEMHNILK KYHQYIVECH GITLLPQFLG
MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN
EGQKIYIDDN NKKVFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE
EGESDGTHPV GTPPDSPGNT LNSSPPLAPG EFDPNIDVYG IKCHENSPRK EVYFMAIIDI
LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF IGHILT
//
MIM
603140
*RECORD*
*FIELD* NO
603140
*FIELD* TI
*603140 PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE II, ALPHA; PIP5K2A
;;PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE, ALPHA; PI5P4KA
read more*FIELD* TX
DESCRIPTION
Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) occupies an
essential position in the phosphoinositide signal transduction cascades
as the precursor to second messengers. Its functions include regulation
of secretion, cell proliferation, differentiation, and motility. The
final step in the synthesis of PtdIns(4,5)P2 is the phosphorylation of
PtdIns(4)P (also known as PIP) by type I PIP kinases, or the
phosphorylation of PtdIns(5)P by type II PIP kinases (EC 2.7.1.149),
such as PIP5K2A (Rameh et al., 1997).
CLONING
Using peptide sequences from purified human erythroid 53-kD type II
PIP5K (PIP5K2A), Boronenkov and Anderson (1995) cloned a human placenta
cDNA encoding PIP5K2A, which they called PIP5KII. The deduced 405-amino
acid protein has a calculated molecular mass of 46,600 Da; the authors
stated that the discrepancy between the calculated and experimental
masses appears to be due to anomalous mobility of PIP5K2A on
SDS-polyacrylamide gels. Although the amino acid sequence of PIP5K2A
does not show homology to known kinases, recombinant PIP5K2A exhibited
kinase activity. PIP5K2A contains a putative Src (190090) homology 3
(SH3) domain-binding sequence. The C-terminal region of PIP5K2A has 34%
and 27% sequence identity with the C-terminal regions of the S.
cerevisiae proteins Mss4 and Fab1, respectively. Northern blot analysis
detected a ubiquitously expressed 4.1-kb PIP5K2A transcript.
By screening a translated DNA database for sequences similar to pig
PtdIns(4)P 5-kinase isoform C peptides, followed by screening a
peripheral blood cell cDNA library, Divecha et al. (1995) cloned human
PIP5K2A. The deduced 406-amino acid protein contains 2 SH3 domains and
has a calculated molecular mass of 46 kD. The amino acid sequence
differs from that reported by Boronenkov and Anderson (1995) between
residues 297 and 311. Northern blot analysis detected a 4.1-kb
transcript in all tissues tested except skeletal muscle and small
intestine. A faint transcript of 2.3 kb was detected in testis.
Bacterially expressed PIP5K2A showed a molecular mass of 46 kD, whereas
the purified pig platelet enzyme had an apparent mass of 53 kD,
suggesting posttranslational modification of the protein in eukaryotes.
GENE FUNCTION
Rameh et al. (1997) characterized the substrate specificity of the red
cell-purified type II PIPK cloned by Boronenkov and Anderson (1995) and
the isoform cloned by Divecha et al. (1995) and compared these to a type
I mouse PIP kinase. Both human type II enzymes converted PtdIns(5)P to
PtdIns(4,5)P2, but they produced virtually no product when PtdIns(4)P
was used as substrate. Rameh et al. (1997) suggested that the earlier
error in characterizing the type II enzyme activity was due to the
presence of contaminating PtdIns(5)P in commercial preparations of
PtdIns(4)P. Rameh et al. (1997) concluded that type I enzymes
preferentially utilize PtdIns(4)P, whereas type II enzymes
preferentially utilize PtdIns(5)P in the production of PtdIns(4,5)P2.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PIP5K2A
gene to chromosome 10 (TMAP STS-H93068).
*FIELD* RF
1. Boronenkov, I. V.; Anderson, R. A.: The sequence of phosphatidylinositol-4-phosphate
5-kinase defines a novel family of lipid kinases. J. Biol. Chem. 270:
2881-2884, 1995.
2. Divecha, N.; Truong, O.; Hsuan, J. J.; Hinchliffe, K. A.; Irvine,
R. F.: The cloning and sequence of the C isoform of PtdIns4P 5-kinase. Biochem.
J. 309: 715-719, 1995.
3. Rameh, L. E.; Tolias, K. F.; Duckworth, B. C.; Cantley, L. C.:
A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390:
192-196, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 10/27/2004
*FIELD* CD
Sheryl A. Jankowski: 10/14/1998
*FIELD* ED
terry: 08/22/2012
wwang: 9/20/2006
alopez: 12/10/2004
mgross: 11/2/2004
terry: 10/27/2004
psherman: 10/14/1998
*RECORD*
*FIELD* NO
603140
*FIELD* TI
*603140 PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE II, ALPHA; PIP5K2A
;;PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE, ALPHA; PI5P4KA
read more*FIELD* TX
DESCRIPTION
Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) occupies an
essential position in the phosphoinositide signal transduction cascades
as the precursor to second messengers. Its functions include regulation
of secretion, cell proliferation, differentiation, and motility. The
final step in the synthesis of PtdIns(4,5)P2 is the phosphorylation of
PtdIns(4)P (also known as PIP) by type I PIP kinases, or the
phosphorylation of PtdIns(5)P by type II PIP kinases (EC 2.7.1.149),
such as PIP5K2A (Rameh et al., 1997).
CLONING
Using peptide sequences from purified human erythroid 53-kD type II
PIP5K (PIP5K2A), Boronenkov and Anderson (1995) cloned a human placenta
cDNA encoding PIP5K2A, which they called PIP5KII. The deduced 405-amino
acid protein has a calculated molecular mass of 46,600 Da; the authors
stated that the discrepancy between the calculated and experimental
masses appears to be due to anomalous mobility of PIP5K2A on
SDS-polyacrylamide gels. Although the amino acid sequence of PIP5K2A
does not show homology to known kinases, recombinant PIP5K2A exhibited
kinase activity. PIP5K2A contains a putative Src (190090) homology 3
(SH3) domain-binding sequence. The C-terminal region of PIP5K2A has 34%
and 27% sequence identity with the C-terminal regions of the S.
cerevisiae proteins Mss4 and Fab1, respectively. Northern blot analysis
detected a ubiquitously expressed 4.1-kb PIP5K2A transcript.
By screening a translated DNA database for sequences similar to pig
PtdIns(4)P 5-kinase isoform C peptides, followed by screening a
peripheral blood cell cDNA library, Divecha et al. (1995) cloned human
PIP5K2A. The deduced 406-amino acid protein contains 2 SH3 domains and
has a calculated molecular mass of 46 kD. The amino acid sequence
differs from that reported by Boronenkov and Anderson (1995) between
residues 297 and 311. Northern blot analysis detected a 4.1-kb
transcript in all tissues tested except skeletal muscle and small
intestine. A faint transcript of 2.3 kb was detected in testis.
Bacterially expressed PIP5K2A showed a molecular mass of 46 kD, whereas
the purified pig platelet enzyme had an apparent mass of 53 kD,
suggesting posttranslational modification of the protein in eukaryotes.
GENE FUNCTION
Rameh et al. (1997) characterized the substrate specificity of the red
cell-purified type II PIPK cloned by Boronenkov and Anderson (1995) and
the isoform cloned by Divecha et al. (1995) and compared these to a type
I mouse PIP kinase. Both human type II enzymes converted PtdIns(5)P to
PtdIns(4,5)P2, but they produced virtually no product when PtdIns(4)P
was used as substrate. Rameh et al. (1997) suggested that the earlier
error in characterizing the type II enzyme activity was due to the
presence of contaminating PtdIns(5)P in commercial preparations of
PtdIns(4)P. Rameh et al. (1997) concluded that type I enzymes
preferentially utilize PtdIns(4)P, whereas type II enzymes
preferentially utilize PtdIns(5)P in the production of PtdIns(4,5)P2.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PIP5K2A
gene to chromosome 10 (TMAP STS-H93068).
*FIELD* RF
1. Boronenkov, I. V.; Anderson, R. A.: The sequence of phosphatidylinositol-4-phosphate
5-kinase defines a novel family of lipid kinases. J. Biol. Chem. 270:
2881-2884, 1995.
2. Divecha, N.; Truong, O.; Hsuan, J. J.; Hinchliffe, K. A.; Irvine,
R. F.: The cloning and sequence of the C isoform of PtdIns4P 5-kinase. Biochem.
J. 309: 715-719, 1995.
3. Rameh, L. E.; Tolias, K. F.; Duckworth, B. C.; Cantley, L. C.:
A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390:
192-196, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 10/27/2004
*FIELD* CD
Sheryl A. Jankowski: 10/14/1998
*FIELD* ED
terry: 08/22/2012
wwang: 9/20/2006
alopez: 12/10/2004
mgross: 11/2/2004
terry: 10/27/2004
psherman: 10/14/1998