Full text data of PIP5K1A
PIP5K1A
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha; PIP5K1-alpha; PtdIns(4)P-5-kinase 1 alpha; 2.7.1.68 (68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha; Phosphatidylinositol 4-phosphate 5-kinase type I alpha; PIP5KIalpha)
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha; PIP5K1-alpha; PtdIns(4)P-5-kinase 1 alpha; 2.7.1.68 (68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha; Phosphatidylinositol 4-phosphate 5-kinase type I alpha; PIP5KIalpha)
UniProt
Q99755
ID PI51A_HUMAN Reviewed; 562 AA.
AC Q99755; A8K4Q0; B4DIN0; Q99754; Q99756;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha;
DE Short=PIP5K1-alpha;
DE Short=PtdIns(4)P-5-kinase 1 alpha;
DE EC=2.7.1.68;
DE AltName: Full=68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha;
DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I alpha;
DE Short=PIP5KIalpha;
GN Name=PIP5K1A;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Fetal brain;
RX PubMed=8955136; DOI=10.1074/jbc.271.51.32937;
RA Loijens J.C., Anderson R.A.;
RT "Type I phosphatidylinositol-4-phosphate 5-kinases are distinct
RT members of this novel lipid kinase family.";
RL J. Biol. Chem. 271:32937-32943(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
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 [6]
RP FUNCTION, AND INTERACTION WITH TUT1.
RX PubMed=18288197; DOI=10.1038/nature06666;
RA Mellman D.L., Gonzales M.L., Song C., Barlow C.A., Wang P.,
RA Kendziorski C., Anderson R.A.;
RT "A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls
RT expression of select mRNAs.";
RL Nature 451:1013-1017(2008).
RN [7]
RP FUNCTION IN KERATINOCYTE DIFFERENTIATION, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN A COMPLEX WITH CDH1; CTNNB1 AND CTNND1.
RX PubMed=19158393; DOI=10.1091/mbc.E08-07-0756;
RA Xie Z., Chang S.M., Pennypacker S.D., Liao E.-Y., Bikle D.D.;
RT "Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates
RT extracellular calcium-induced keratinocyte differentiation.";
RL Mol. Biol. Cell 20:1695-1704(2009).
RN [8]
RP FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-322 AND ARG-440.
RX PubMed=20660631; DOI=10.1083/jcb.200911110;
RA Chao W.-T., Daquinag A.C., Ashcroft F., Kunz J.;
RT "Type I PIPK-alpha regulates directed cell migration by modulating
RT Rac1 plasma membrane targeting and activation.";
RL J. Cell Biol. 190:247-262(2010).
RN [9]
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 4-
CC phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of
CC cellular processes and is the substrate to form
CC phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3),
CC another second messenger. The majority of PtdIns(4,5)P2 is thought
CC to occur via type I phosphatidylinositol 4-phosphate 5-kinases
CC given the abundance of PtdIns4P. Participates in a variety of
CC cellular processes such as actin cytoskeleton organization, cell
CC adhesion, migration and phagocytosis. Required for membrane
CC ruffling formation, actin organization and focal adhesion
CC formation during directional cell migration by controlling
CC integrin-induced translocation of RAC1 to the plasma membrane.
CC Together with PIP5K1C is required for phagocytosis, but they
CC regulate different types of actin remodeling at sequential steps.
CC Promotes particle ingestion by activating WAS that induces Arp2/3
CC dependent actin polymerization at the nascent phagocytic cup.
CC Together with PIP5K1B is required after stimulation of G-protein
CC coupled receptors for stable platelet adhesion. Plays a role
CC during calcium-induced keratinocyte differentiation. Recruited to
CC the plasma membrane by the E-cadherin/beta-catenin complex where
CC it provides the substrate PtdIns(4,5)P2 for the production of
CC PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate
CC that mobilize internal calcium and drive keratinocyte
CC differentiation. Together with PIP5K1C have a role during
CC embryogenesis. Functions also in the nucleus where acts as an
CC activator of TUT1 adenylyltransferase activity in nuclear
CC speckles, thereby regulating mRNA polyadenylation of a select set
CC of mRNAs.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4-
CC phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
CC -!- SUBUNIT: Interacts with RAC1 (By similarity). Interacts with TUT1.
CC Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and
CC CTNND1 at the plasma membrane upon calcium stimulation.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm (By similarity).
CC Nucleus speckle. Cell projection, ruffle. Note=Colocalizes with
CC RAC1 at actin-rich membrane ruffles. Localizes to nuclear speckles
CC and associates with TUT1 to regulate polyadenylation of selected
CC mRNAs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PIP5KIalpha2;
CC IsoId=Q99755-1; Sequence=Displayed;
CC Name=2; Synonyms=PIP5KIalpha3;
CC IsoId=Q99755-2; Sequence=VSP_016007, VSP_016008;
CC Name=3;
CC IsoId=Q99755-3; Sequence=VSP_016007;
CC Name=4;
CC IsoId=Q99755-4; Sequence=VSP_041912, VSP_041913;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal
CC muscle, kidney and pancreas. Detected at lower levels in brain,
CC lung and liver.
CC -!- SIMILARITY: Contains 1 PIPK domain.
CC -!- CAUTION: There is confusion in the literature with
CC phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due
CC to the fact that frequently mouse PIP5K1B is named
CC Phosphatidylinositol 4-phosphate 5-kinase type I alpha.
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DR EMBL; U78575; AAC50910.1; -; mRNA.
DR EMBL; U78576; AAC50911.1; -; mRNA.
DR EMBL; U78577; AAC50912.1; -; mRNA.
DR EMBL; AK291015; BAF83704.1; -; mRNA.
DR EMBL; AK295691; BAG58542.1; -; mRNA.
DR EMBL; AL592424; CAI16386.1; -; Genomic_DNA.
DR EMBL; AL592424; CAI16387.1; -; Genomic_DNA.
DR EMBL; AL592424; CAI16388.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53461.1; -; Genomic_DNA.
DR EMBL; BC007833; AAH07833.1; -; mRNA.
DR RefSeq; NP_001129108.1; NM_001135636.1.
DR RefSeq; NP_001129109.1; NM_001135637.1.
DR RefSeq; NP_001129110.1; NM_001135638.1.
DR RefSeq; NP_003548.1; NM_003557.2.
DR UniGene; Hs.655131; -.
DR UniGene; Hs.661888; -.
DR ProteinModelPortal; Q99755; -.
DR SMR; Q99755; 82-367.
DR IntAct; Q99755; 2.
DR MINT; MINT-1406942; -.
DR STRING; 9606.ENSP00000357883; -.
DR BindingDB; Q99755; -.
DR ChEMBL; CHEMBL5969; -.
DR GuidetoPHARMACOLOGY; 2164; -.
DR PhosphoSite; Q99755; -.
DR DMDM; 74752158; -.
DR PaxDb; Q99755; -.
DR PRIDE; Q99755; -.
DR DNASU; 8394; -.
DR Ensembl; ENST00000349792; ENSP00000271663; ENSG00000143398.
DR Ensembl; ENST00000368888; ENSP00000357883; ENSG00000143398.
DR Ensembl; ENST00000368890; ENSP00000357885; ENSG00000143398.
DR Ensembl; ENST00000441902; ENSP00000415648; ENSG00000143398.
DR GeneID; 8394; -.
DR KEGG; hsa:8394; -.
DR UCSC; uc001exj.3; human.
DR CTD; 8394; -.
DR GeneCards; GC01P151170; -.
DR HGNC; HGNC:8994; PIP5K1A.
DR HPA; HPA029366; -.
DR MIM; 603275; gene.
DR neXtProt; NX_Q99755; -.
DR PharmGKB; PA33327; -.
DR eggNOG; COG5148; -.
DR HOGENOM; HOG000193876; -.
DR HOVERGEN; HBG052818; -.
DR InParanoid; Q99755; -.
DR KO; K00889; -.
DR OMA; ETEDHMG; -.
DR OrthoDB; EOG70W3DM; -.
DR BioCyc; MetaCyc:HS07047-MONOMER; -.
DR BRENDA; 2.7.1.68; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; Q99755; -.
DR ChiTaRS; PIP5K1A; human.
DR GeneWiki; PIP5K1A; -.
DR GenomeRNAi; 8394; -.
DR NextBio; 31416; -.
DR PMAP-CutDB; Q99755; -.
DR PRO; PR:Q99755; -.
DR ArrayExpress; Q99755; -.
DR Bgee; Q99755; -.
DR CleanEx; HS_PIP5K1A; -.
DR Genevestigator; Q99755; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0032863; P:activation of Rac GTPase activity; IMP:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; TAS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; TAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IMP:UniProtKB.
DR GO; GO:0097178; P:ruffle assembly; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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 Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Isopeptide bond; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1 562 Phosphatidylinositol 4-phosphate 5-kinase
FT type-1 alpha.
FT /FTId=PRO_0000185456.
FT DOMAIN 81 449 PIPK.
FT CROSSLNK 103 103 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 30 52 ASGIKRPMASEVLEARQDSYISL -> SGIKRPMASE (in
FT isoform 2 and isoform 3).
FT /FTId=VSP_016007.
FT VAR_SEQ 41 52 Missing (in isoform 4).
FT /FTId=VSP_041912.
FT VAR_SEQ 382 410 HMGGIPARNSKGERLLLYIGIIDILQSYR -> Q (in
FT isoform 4).
FT /FTId=VSP_041913.
FT VAR_SEQ 455 504 LKPSPSKKFRSGSSFSRRAGSSGNSCITYQPSVSGEHKAQV
FT TTKAEVEPG -> C (in isoform 2).
FT /FTId=VSP_016008.
FT MUTAGEN 322 322 D->N: Does not affect targeting of RAC1
FT to the plasma membrane; when associated
FT with Q-440.
FT MUTAGEN 440 440 R->Q: Does not affect targeting of RAC1
FT to the plasma membrane; when associated
FT with N-322.
FT CONFLICT 257 257 K -> E (in Ref. 2; BAG58542).
SQ SEQUENCE 562 AA; 62633 MW; A8F7988EB73506A0 CRC64;
MASASSGPSS SVGFSSFDPA VPSCTLSSAA SGIKRPMASE VLEARQDSYI SLVPYASGMP
IKKIGHRSVD SSGETTYKKT TSSALKGAIQ LGITHTVGSL STKPERDVLM QDFYVVESIF
FPSEGSNLTP AHHYNDFRFK TYAPVAFRYF RELFGIRPDD YLYSLCSEPL IELCSSGASG
SLFYVSSDDE FIIKTVQHKE AEFLQKLLPG YYMNLNQNPR TLLPKFYGLY CVQAGGKNIR
IVVMNNLLPR SVKMHIKYDL KGSTYKRRAS QKEREKPLPT FKDLDFLQDI PDGLFLDADM
YNALCKTLQR DCLVLQSFKI MDYSLLMSIH NIDHAQREPL SSETQYSVDT RRPAPQKALY
STAMESIQGE ARRGGTMETD DHMGGIPARN SKGERLLLYI GIIDILQSYR FVKKLEHSWK
ALVHDGDTVS VHRPGFYAER FQRFMCNTVF KKIPLKPSPS KKFRSGSSFS RRAGSSGNSC
ITYQPSVSGE HKAQVTTKAE VEPGVHLGRP DVLPQTPPLE EISEGSPIPD PSFSPLVGET
LQMLTTSTTL EKLEVAESEF TH
//
ID PI51A_HUMAN Reviewed; 562 AA.
AC Q99755; A8K4Q0; B4DIN0; Q99754; Q99756;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha;
DE Short=PIP5K1-alpha;
DE Short=PtdIns(4)P-5-kinase 1 alpha;
DE EC=2.7.1.68;
DE AltName: Full=68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha;
DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I alpha;
DE Short=PIP5KIalpha;
GN Name=PIP5K1A;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Fetal brain;
RX PubMed=8955136; DOI=10.1074/jbc.271.51.32937;
RA Loijens J.C., Anderson R.A.;
RT "Type I phosphatidylinositol-4-phosphate 5-kinases are distinct
RT members of this novel lipid kinase family.";
RL J. Biol. Chem. 271:32937-32943(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
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 [6]
RP FUNCTION, AND INTERACTION WITH TUT1.
RX PubMed=18288197; DOI=10.1038/nature06666;
RA Mellman D.L., Gonzales M.L., Song C., Barlow C.A., Wang P.,
RA Kendziorski C., Anderson R.A.;
RT "A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls
RT expression of select mRNAs.";
RL Nature 451:1013-1017(2008).
RN [7]
RP FUNCTION IN KERATINOCYTE DIFFERENTIATION, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN A COMPLEX WITH CDH1; CTNNB1 AND CTNND1.
RX PubMed=19158393; DOI=10.1091/mbc.E08-07-0756;
RA Xie Z., Chang S.M., Pennypacker S.D., Liao E.-Y., Bikle D.D.;
RT "Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates
RT extracellular calcium-induced keratinocyte differentiation.";
RL Mol. Biol. Cell 20:1695-1704(2009).
RN [8]
RP FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-322 AND ARG-440.
RX PubMed=20660631; DOI=10.1083/jcb.200911110;
RA Chao W.-T., Daquinag A.C., Ashcroft F., Kunz J.;
RT "Type I PIPK-alpha regulates directed cell migration by modulating
RT Rac1 plasma membrane targeting and activation.";
RL J. Cell Biol. 190:247-262(2010).
RN [9]
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 4-
CC phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of
CC cellular processes and is the substrate to form
CC phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3),
CC another second messenger. The majority of PtdIns(4,5)P2 is thought
CC to occur via type I phosphatidylinositol 4-phosphate 5-kinases
CC given the abundance of PtdIns4P. Participates in a variety of
CC cellular processes such as actin cytoskeleton organization, cell
CC adhesion, migration and phagocytosis. Required for membrane
CC ruffling formation, actin organization and focal adhesion
CC formation during directional cell migration by controlling
CC integrin-induced translocation of RAC1 to the plasma membrane.
CC Together with PIP5K1C is required for phagocytosis, but they
CC regulate different types of actin remodeling at sequential steps.
CC Promotes particle ingestion by activating WAS that induces Arp2/3
CC dependent actin polymerization at the nascent phagocytic cup.
CC Together with PIP5K1B is required after stimulation of G-protein
CC coupled receptors for stable platelet adhesion. Plays a role
CC during calcium-induced keratinocyte differentiation. Recruited to
CC the plasma membrane by the E-cadherin/beta-catenin complex where
CC it provides the substrate PtdIns(4,5)P2 for the production of
CC PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate
CC that mobilize internal calcium and drive keratinocyte
CC differentiation. Together with PIP5K1C have a role during
CC embryogenesis. Functions also in the nucleus where acts as an
CC activator of TUT1 adenylyltransferase activity in nuclear
CC speckles, thereby regulating mRNA polyadenylation of a select set
CC of mRNAs.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4-
CC phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
CC -!- SUBUNIT: Interacts with RAC1 (By similarity). Interacts with TUT1.
CC Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and
CC CTNND1 at the plasma membrane upon calcium stimulation.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm (By similarity).
CC Nucleus speckle. Cell projection, ruffle. Note=Colocalizes with
CC RAC1 at actin-rich membrane ruffles. Localizes to nuclear speckles
CC and associates with TUT1 to regulate polyadenylation of selected
CC mRNAs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PIP5KIalpha2;
CC IsoId=Q99755-1; Sequence=Displayed;
CC Name=2; Synonyms=PIP5KIalpha3;
CC IsoId=Q99755-2; Sequence=VSP_016007, VSP_016008;
CC Name=3;
CC IsoId=Q99755-3; Sequence=VSP_016007;
CC Name=4;
CC IsoId=Q99755-4; Sequence=VSP_041912, VSP_041913;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal
CC muscle, kidney and pancreas. Detected at lower levels in brain,
CC lung and liver.
CC -!- SIMILARITY: Contains 1 PIPK domain.
CC -!- CAUTION: There is confusion in the literature with
CC phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due
CC to the fact that frequently mouse PIP5K1B is named
CC Phosphatidylinositol 4-phosphate 5-kinase type I alpha.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; U78575; AAC50910.1; -; mRNA.
DR EMBL; U78576; AAC50911.1; -; mRNA.
DR EMBL; U78577; AAC50912.1; -; mRNA.
DR EMBL; AK291015; BAF83704.1; -; mRNA.
DR EMBL; AK295691; BAG58542.1; -; mRNA.
DR EMBL; AL592424; CAI16386.1; -; Genomic_DNA.
DR EMBL; AL592424; CAI16387.1; -; Genomic_DNA.
DR EMBL; AL592424; CAI16388.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53461.1; -; Genomic_DNA.
DR EMBL; BC007833; AAH07833.1; -; mRNA.
DR RefSeq; NP_001129108.1; NM_001135636.1.
DR RefSeq; NP_001129109.1; NM_001135637.1.
DR RefSeq; NP_001129110.1; NM_001135638.1.
DR RefSeq; NP_003548.1; NM_003557.2.
DR UniGene; Hs.655131; -.
DR UniGene; Hs.661888; -.
DR ProteinModelPortal; Q99755; -.
DR SMR; Q99755; 82-367.
DR IntAct; Q99755; 2.
DR MINT; MINT-1406942; -.
DR STRING; 9606.ENSP00000357883; -.
DR BindingDB; Q99755; -.
DR ChEMBL; CHEMBL5969; -.
DR GuidetoPHARMACOLOGY; 2164; -.
DR PhosphoSite; Q99755; -.
DR DMDM; 74752158; -.
DR PaxDb; Q99755; -.
DR PRIDE; Q99755; -.
DR DNASU; 8394; -.
DR Ensembl; ENST00000349792; ENSP00000271663; ENSG00000143398.
DR Ensembl; ENST00000368888; ENSP00000357883; ENSG00000143398.
DR Ensembl; ENST00000368890; ENSP00000357885; ENSG00000143398.
DR Ensembl; ENST00000441902; ENSP00000415648; ENSG00000143398.
DR GeneID; 8394; -.
DR KEGG; hsa:8394; -.
DR UCSC; uc001exj.3; human.
DR CTD; 8394; -.
DR GeneCards; GC01P151170; -.
DR HGNC; HGNC:8994; PIP5K1A.
DR HPA; HPA029366; -.
DR MIM; 603275; gene.
DR neXtProt; NX_Q99755; -.
DR PharmGKB; PA33327; -.
DR eggNOG; COG5148; -.
DR HOGENOM; HOG000193876; -.
DR HOVERGEN; HBG052818; -.
DR InParanoid; Q99755; -.
DR KO; K00889; -.
DR OMA; ETEDHMG; -.
DR OrthoDB; EOG70W3DM; -.
DR BioCyc; MetaCyc:HS07047-MONOMER; -.
DR BRENDA; 2.7.1.68; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; Q99755; -.
DR ChiTaRS; PIP5K1A; human.
DR GeneWiki; PIP5K1A; -.
DR GenomeRNAi; 8394; -.
DR NextBio; 31416; -.
DR PMAP-CutDB; Q99755; -.
DR PRO; PR:Q99755; -.
DR ArrayExpress; Q99755; -.
DR Bgee; Q99755; -.
DR CleanEx; HS_PIP5K1A; -.
DR Genevestigator; Q99755; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0032863; P:activation of Rac GTPase activity; IMP:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; TAS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; TAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IMP:UniProtKB.
DR GO; GO:0097178; P:ruffle assembly; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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 Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Isopeptide bond; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1 562 Phosphatidylinositol 4-phosphate 5-kinase
FT type-1 alpha.
FT /FTId=PRO_0000185456.
FT DOMAIN 81 449 PIPK.
FT CROSSLNK 103 103 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 30 52 ASGIKRPMASEVLEARQDSYISL -> SGIKRPMASE (in
FT isoform 2 and isoform 3).
FT /FTId=VSP_016007.
FT VAR_SEQ 41 52 Missing (in isoform 4).
FT /FTId=VSP_041912.
FT VAR_SEQ 382 410 HMGGIPARNSKGERLLLYIGIIDILQSYR -> Q (in
FT isoform 4).
FT /FTId=VSP_041913.
FT VAR_SEQ 455 504 LKPSPSKKFRSGSSFSRRAGSSGNSCITYQPSVSGEHKAQV
FT TTKAEVEPG -> C (in isoform 2).
FT /FTId=VSP_016008.
FT MUTAGEN 322 322 D->N: Does not affect targeting of RAC1
FT to the plasma membrane; when associated
FT with Q-440.
FT MUTAGEN 440 440 R->Q: Does not affect targeting of RAC1
FT to the plasma membrane; when associated
FT with N-322.
FT CONFLICT 257 257 K -> E (in Ref. 2; BAG58542).
SQ SEQUENCE 562 AA; 62633 MW; A8F7988EB73506A0 CRC64;
MASASSGPSS SVGFSSFDPA VPSCTLSSAA SGIKRPMASE VLEARQDSYI SLVPYASGMP
IKKIGHRSVD SSGETTYKKT TSSALKGAIQ LGITHTVGSL STKPERDVLM QDFYVVESIF
FPSEGSNLTP AHHYNDFRFK TYAPVAFRYF RELFGIRPDD YLYSLCSEPL IELCSSGASG
SLFYVSSDDE FIIKTVQHKE AEFLQKLLPG YYMNLNQNPR TLLPKFYGLY CVQAGGKNIR
IVVMNNLLPR SVKMHIKYDL KGSTYKRRAS QKEREKPLPT FKDLDFLQDI PDGLFLDADM
YNALCKTLQR DCLVLQSFKI MDYSLLMSIH NIDHAQREPL SSETQYSVDT RRPAPQKALY
STAMESIQGE ARRGGTMETD DHMGGIPARN SKGERLLLYI GIIDILQSYR FVKKLEHSWK
ALVHDGDTVS VHRPGFYAER FQRFMCNTVF KKIPLKPSPS KKFRSGSSFS RRAGSSGNSC
ITYQPSVSGE HKAQVTTKAE VEPGVHLGRP DVLPQTPPLE EISEGSPIPD PSFSPLVGET
LQMLTTSTTL EKLEVAESEF TH
//
MIM
603275
*RECORD*
*FIELD* NO
603275
*FIELD* TI
*603275 PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE I, ALPHA; PIP5K1A
*FIELD* TX
read more
DESCRIPTION
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) synthesize
phosphatidylinositol 4,5-bisphosphate by phosphorylating
phosphatidylinositol 4-phosphate. See 603261.
CLONING
By searching sequence databases with peptide sequences obtained from the
68-kD type I PIP5K purified from bovine erythrocytes, Loijens and
Anderson (1996) identified a human EST encoding PIP5K1A, which they
called PIP5KI-alpha. They screened a human fetal brain cDNA library and
isolated full-length PIP5K1A cDNAs. The deduced 549-amino acid protein
has the conserved kinase homology domain of PIP5K family members. Within
this domain, PIP5K1A shows 83% and 35% amino acid identity with PIP5K1B
(602745) and PIP5K2A (603140), respectively. Overall, the PIP5K1A and
PIP5K1B proteins are 64% identical. Recombinant PIP5K1A expressed in
bacteria had a molecular mass of approximately 66.3 kD by Western blot
analysis. The authors isolated additional PIP5K1A cDNAs which they
suggested represent splicing isoforms. Northern blot analysis detected a
major 4.2-kb PIP5K1A transcript which had a wide tissue distribution.
GENE FUNCTION
Using deletion mutant analysis, Ishihara et al. (1998) identified an
approximately 380-amino acid minimal core sequence of mouse Pip5k1a that
was sufficient for phosphatidylinositol 4-phosphate kinase activity.
Overexpression of mouse Pip5k1a in COS-7 cells induced an increase in
short actin fibers and a decrease in actin stress fibers.
To determine roles for nuclear phosphatidylinositol 4,5-bisphosphate
(PtdIns4,5P(2)), Mellman et al. (2008) set out to identify proteins that
interact with the nuclear PIPK, PIPK1A. Mellman et al. (2008) found that
PIPK1A colocalizes at nuclear speckles and interacts with a noncanonical
poly(A) polymerase, TUT1 (610641), which they termed Star-PAP for
'nuclear speckle-targeted PIPK1A-regulated poly(A) polymerase,' and that
the activity of TUT1 can be specifically regulated by PtdIns4,5P(2).
TUT1 and PIPK1A function together in a complex to control the expression
of select mRNAs, including the transcript encoding the key
cytoprotective enzyme heme oxygenase-1 (141250) and other oxidative
stress response genes, by regulating the 3-prime-end formation of their
mRNAs. Mellman et al. (2008) concluded that, taken together, the data
demonstrated a model by which phosphoinositide signaling works in tandem
with complement pathways to regulate the activity of TUT1 (Star-PAP) and
the subsequent biosynthesis of its target mRNA. Mellman et al. (2008)
suggested that their results revealed a mechanism for the integration of
nuclear phosphoinositide signals and a method for regulating gene
expression.
By screening a human kinase small interfering RNA library, Pan et al.
(2008) identified phosphatidylinositol 4-kinase type II-alpha (PI4K2A;
609763) and phosphatidylinositol 4-phosphate 5-kinase type I (PIP5KI) as
required for Wnt3a (606359)-induced LRP6 (603507) phosphorylation at
ser1490 in mammalian cells and confirmed that these kinases are
important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the
formation of phosphatidylinositol 4,5-bisphosphates through 'frizzled'
(see 603408) and 'dishevelled' (see 601365), the latter of which
directly interacted with and activated PIP5KI. In turn,
phosphatidylinositol 4,5-bisphosphates regulated phosphorylation of LRP6
at thr1479 and ser1490. Pan et al. (2008) concluded that their study
revealed a signaling mechanism for Wnt to regulate LRP6 phosphorylation.
MAPPING
Xie et al. (2000) localized the PIP5K1A gene to chromosome 1q22-q24 by
FISH.
*FIELD* RF
1. Ishihara, H.; Shibasaki, Y.; Kizuki, N.; Wada, T.; Yazaki, Y.;
Asano, T.; Oka, Y.: Type I phosphatidylinositol-4-phosphate 5-kinases:
cloning of the third isoform and deletion/substitution analysis of
members of this novel lipid kinase family. J. Biol. Chem. 273: 8741-8748,
1998.
2. Loijens, J. C.; Anderson, R. A.: Type I phosphatidylinositol-4-phosphate
5-kinases are distinct members of this novel lipid kinase family. J.
Biol. Chem. 271: 32937-32943, 1996.
3. Mellman, D. L.; Gonzales, M. L.; Song, C.; Barlow, C. A.; Wang,
P.; Kendziorski, C.; Anderson, R. A.: A PtdIns4,5P(2)-regulated nuclear
poly(A) polymerase controls expression of select mRNAs. Nature 451:
1013-1017, 2008.
4. Pan, W.; Choi, S.-C.; Wang, H.; Qin, Y.; Volpicelli-Daley, L.;
Swan, L.; Lucast, L.; Khoo, C.; Zhang, X.; Li, L.; Abrams, C. S.;
Sokol, S. Y.; Wu, D.: Wnt3a-mediated formation of phosphatidylinositol
4,5-bisphosphate regulates LRP6 phosphorylation. Science 321: 1350-1353,
2008.
5. Xie, Y.; Zhu, L.; Zhao, G.: Assignment of type I phosphatidylinositol-4-phosphate
5-kinase (PIP5K1A) to human chromosome bands 1q22-q24 by in situ hybridization. Cytogenet.
Cell Genet. 88: 197-199, 2000.
*FIELD* CN
Ada Hamosh - updated: 10/1/2008
Patricia A. Hartz - updated: 3/18/2008
Dawn Watkins-Chow - updated: 7/11/2001
Joanna S. Amberger - updated: 4/19/2001
*FIELD* CD
Patti M. Sherman: 11/10/1998
*FIELD* ED
alopez: 09/04/2012
terry: 8/29/2012
terry: 8/22/2012
carol: 6/21/2012
alopez: 10/2/2008
terry: 10/1/2008
alopez: 3/26/2008
terry: 3/18/2008
terry: 7/20/2004
mgross: 7/11/2001
terry: 4/20/2001
joanna: 4/19/2001
carol: 11/13/1998
*RECORD*
*FIELD* NO
603275
*FIELD* TI
*603275 PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE I, ALPHA; PIP5K1A
*FIELD* TX
read more
DESCRIPTION
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) synthesize
phosphatidylinositol 4,5-bisphosphate by phosphorylating
phosphatidylinositol 4-phosphate. See 603261.
CLONING
By searching sequence databases with peptide sequences obtained from the
68-kD type I PIP5K purified from bovine erythrocytes, Loijens and
Anderson (1996) identified a human EST encoding PIP5K1A, which they
called PIP5KI-alpha. They screened a human fetal brain cDNA library and
isolated full-length PIP5K1A cDNAs. The deduced 549-amino acid protein
has the conserved kinase homology domain of PIP5K family members. Within
this domain, PIP5K1A shows 83% and 35% amino acid identity with PIP5K1B
(602745) and PIP5K2A (603140), respectively. Overall, the PIP5K1A and
PIP5K1B proteins are 64% identical. Recombinant PIP5K1A expressed in
bacteria had a molecular mass of approximately 66.3 kD by Western blot
analysis. The authors isolated additional PIP5K1A cDNAs which they
suggested represent splicing isoforms. Northern blot analysis detected a
major 4.2-kb PIP5K1A transcript which had a wide tissue distribution.
GENE FUNCTION
Using deletion mutant analysis, Ishihara et al. (1998) identified an
approximately 380-amino acid minimal core sequence of mouse Pip5k1a that
was sufficient for phosphatidylinositol 4-phosphate kinase activity.
Overexpression of mouse Pip5k1a in COS-7 cells induced an increase in
short actin fibers and a decrease in actin stress fibers.
To determine roles for nuclear phosphatidylinositol 4,5-bisphosphate
(PtdIns4,5P(2)), Mellman et al. (2008) set out to identify proteins that
interact with the nuclear PIPK, PIPK1A. Mellman et al. (2008) found that
PIPK1A colocalizes at nuclear speckles and interacts with a noncanonical
poly(A) polymerase, TUT1 (610641), which they termed Star-PAP for
'nuclear speckle-targeted PIPK1A-regulated poly(A) polymerase,' and that
the activity of TUT1 can be specifically regulated by PtdIns4,5P(2).
TUT1 and PIPK1A function together in a complex to control the expression
of select mRNAs, including the transcript encoding the key
cytoprotective enzyme heme oxygenase-1 (141250) and other oxidative
stress response genes, by regulating the 3-prime-end formation of their
mRNAs. Mellman et al. (2008) concluded that, taken together, the data
demonstrated a model by which phosphoinositide signaling works in tandem
with complement pathways to regulate the activity of TUT1 (Star-PAP) and
the subsequent biosynthesis of its target mRNA. Mellman et al. (2008)
suggested that their results revealed a mechanism for the integration of
nuclear phosphoinositide signals and a method for regulating gene
expression.
By screening a human kinase small interfering RNA library, Pan et al.
(2008) identified phosphatidylinositol 4-kinase type II-alpha (PI4K2A;
609763) and phosphatidylinositol 4-phosphate 5-kinase type I (PIP5KI) as
required for Wnt3a (606359)-induced LRP6 (603507) phosphorylation at
ser1490 in mammalian cells and confirmed that these kinases are
important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the
formation of phosphatidylinositol 4,5-bisphosphates through 'frizzled'
(see 603408) and 'dishevelled' (see 601365), the latter of which
directly interacted with and activated PIP5KI. In turn,
phosphatidylinositol 4,5-bisphosphates regulated phosphorylation of LRP6
at thr1479 and ser1490. Pan et al. (2008) concluded that their study
revealed a signaling mechanism for Wnt to regulate LRP6 phosphorylation.
MAPPING
Xie et al. (2000) localized the PIP5K1A gene to chromosome 1q22-q24 by
FISH.
*FIELD* RF
1. Ishihara, H.; Shibasaki, Y.; Kizuki, N.; Wada, T.; Yazaki, Y.;
Asano, T.; Oka, Y.: Type I phosphatidylinositol-4-phosphate 5-kinases:
cloning of the third isoform and deletion/substitution analysis of
members of this novel lipid kinase family. J. Biol. Chem. 273: 8741-8748,
1998.
2. Loijens, J. C.; Anderson, R. A.: Type I phosphatidylinositol-4-phosphate
5-kinases are distinct members of this novel lipid kinase family. J.
Biol. Chem. 271: 32937-32943, 1996.
3. Mellman, D. L.; Gonzales, M. L.; Song, C.; Barlow, C. A.; Wang,
P.; Kendziorski, C.; Anderson, R. A.: A PtdIns4,5P(2)-regulated nuclear
poly(A) polymerase controls expression of select mRNAs. Nature 451:
1013-1017, 2008.
4. Pan, W.; Choi, S.-C.; Wang, H.; Qin, Y.; Volpicelli-Daley, L.;
Swan, L.; Lucast, L.; Khoo, C.; Zhang, X.; Li, L.; Abrams, C. S.;
Sokol, S. Y.; Wu, D.: Wnt3a-mediated formation of phosphatidylinositol
4,5-bisphosphate regulates LRP6 phosphorylation. Science 321: 1350-1353,
2008.
5. Xie, Y.; Zhu, L.; Zhao, G.: Assignment of type I phosphatidylinositol-4-phosphate
5-kinase (PIP5K1A) to human chromosome bands 1q22-q24 by in situ hybridization. Cytogenet.
Cell Genet. 88: 197-199, 2000.
*FIELD* CN
Ada Hamosh - updated: 10/1/2008
Patricia A. Hartz - updated: 3/18/2008
Dawn Watkins-Chow - updated: 7/11/2001
Joanna S. Amberger - updated: 4/19/2001
*FIELD* CD
Patti M. Sherman: 11/10/1998
*FIELD* ED
alopez: 09/04/2012
terry: 8/29/2012
terry: 8/22/2012
carol: 6/21/2012
alopez: 10/2/2008
terry: 10/1/2008
alopez: 3/26/2008
terry: 3/18/2008
terry: 7/20/2004
mgross: 7/11/2001
terry: 4/20/2001
joanna: 4/19/2001
carol: 11/13/1998