PI51A_RAT
ID PI51A_RAT Reviewed; 546 AA.
AC D3ZSI8;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha {ECO:0000250|UniProtKB:Q99755};
DE Short=PIP5K1-alpha {ECO:0000250|UniProtKB:Q99755};
DE Short=PtdIns(4)P-5-kinase 1 alpha {ECO:0000250|UniProtKB:Q99755};
DE EC=2.7.1.68 {ECO:0000250|UniProtKB:Q99755};
DE AltName: Full=68 kDa type I phosphatidylinositol 4-phosphate 5-kinase {ECO:0000250|UniProtKB:Q99755};
DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I alpha {ECO:0000250|UniProtKB:Q99755};
DE Short=PIP5KIalpha {ECO:0000250|UniProtKB:Q99755};
GN Name=Pip5k1a {ECO:0000312|RGD:1306127};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Soares M.B., Casavant T.L., Sheffield V.C., Bonaldo M.F., Bair T.B.,
RA Scheetz T.E., Snir E., Akabogu I., Bair J.L., Berger B., Crouch K.,
RA Davis A., Eystone M.E., Keppel C., Kucaba T.A., Lebeck M., Lin J.L.,
RA de Melo A.I.R., Rehmann J., Reiter R.S., Schaefer K., Smith C., Tack D.,
RA Trout K., Lin J.J.-C.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP INTERACTION WITH DGKZ.
RX PubMed=15157668; DOI=10.1016/j.cellsig.2004.01.010;
RA Luo B., Prescott S.M., Topham M.K.;
RT "Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-
RT kinase Ialpha by a novel mechanism.";
RL Cell. Signal. 16:891-897(2004).
CC -!- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 4-
CC phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-
CC bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that
CC regulates several cellular processes such as signal transduction,
CC vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and
CC cell motility. PtdIns(4,5)P2 can directly act as a second messenger or
CC can be utilized as a precursor to generate other second messengers:
CC inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or
CC phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (By
CC similarity). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the
CC predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can
CC also use phosphatidylinositol (PtdIns) as substrate in vitro (By
CC similarity). Together with PIP5K1C, is required for phagocytosis, both
CC enzymes regulating different types of actin remodeling at sequential
CC steps. Promotes particle ingestion by activating the WAS GTPase-binding
CC protein that induces Arp2/3 dependent actin polymerization at the
CC nascent phagocytic cup. Together with PIP5K1B, is required, after
CC stimulation by G-protein coupled receptors, for the synthesis of IP3
CC that will induce stable platelet adhesion (By similarity). Recruited to
CC the plasma membrane by the E-cadherin/beta-catenin complex where it
CC provides the substrate PtdIns(4,5)P2 for the production of
CC PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and
CC drive keratinocyte differentiation (By similarity). Positively
CC regulates insulin-induced translocation of SLC2A4 to the cell membrane
CC in adipocytes. Together with PIP5K1C has a role during embryogenesis
CC (By similarity). Independently of its catalytic activity, is required
CC for membrane ruffling formation, actin organization and focal adhesion
CC formation during directional cell migration by controlling integrin-
CC induced translocation of the small GTPase RAC1 to the plasma membrane.
CC Also functions in the nucleus where it acts as an activator of TUT1
CC adenylyltransferase activity in nuclear speckles, thereby regulating
CC mRNA polyadenylation of a select set of mRNAs (By similarity).
CC {ECO:0000250|UniProtKB:P70182, ECO:0000250|UniProtKB:Q99755}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:14425,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.68;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14426;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol
CC 4,5-bisphosphate + ADP + H(+); Xref=Rhea:RHEA:40363,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77136,
CC ChEBI:CHEBI:77137, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40364;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4-
CC phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:65356,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83423,
CC ChEBI:CHEBI:83436, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65357;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-
CC myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-
CC sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40367, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77139, ChEBI:CHEBI:77140, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40368;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-
CC myo-inositol + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-
CC phospho-1D-myo-inositol 5-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40379, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77163, ChEBI:CHEBI:77164, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40380;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-
CC phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z,12Z)-
CC octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate +
CC ADP + H(+); Xref=Rhea:RHEA:40383, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77158, ChEBI:CHEBI:77159,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40384;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phospho-(1D-myo-inositol) + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate +
CC ADP + H(+); Xref=Rhea:RHEA:40375, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77160, ChEBI:CHEBI:133606,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40376;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-
CC inositol + ATP = 1,2-di(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-
CC 1D-myo-inositol 5-phosphate + ADP + H(+); Xref=Rhea:RHEA:40387,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77165,
CC ChEBI:CHEBI:77167, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40388;
CC Evidence={ECO:0000250|UniProtKB:Q99755};
CC -!- SUBUNIT: Interacts with RAC1. Interacts with TUT1. Forms a complex with
CC CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane
CC upon calcium stimulation (By similarity). Found in a ternary complex
CC with IRS1 and DGKZ in the absence of insulin stimulation (By
CC similarity). Interacts with DGKZ (PubMed:15157668). Interacts with
CC PIP4K2C; the interaction inhibits PIP5K1A kinase activity (By
CC similarity). {ECO:0000250|UniProtKB:P70182,
CC ECO:0000250|UniProtKB:Q99755, ECO:0000269|PubMed:15157668}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P70182}.
CC Cytoplasm {ECO:0000250|UniProtKB:P70182}. Nucleus
CC {ECO:0000250|UniProtKB:Q99755}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q99755}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q99755}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q99755}. Note=Colocalizes with RAC1 at actin-
CC rich membrane ruffles. Localizes to nuclear speckles and associates
CC with TUT1 to regulate polyadenylation of selected mRNAs.
CC {ECO:0000250|UniProtKB:Q99755}.
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DR EMBL; AY724476; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AABR06019271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; D3ZSI8; -.
DR SMR; D3ZSI8; -.
DR STRING; 10116.ENSRNOP00000028609; -.
DR iPTMnet; D3ZSI8; -.
DR PhosphoSitePlus; D3ZSI8; -.
DR PaxDb; D3ZSI8; -.
DR PeptideAtlas; D3ZSI8; -.
DR PRIDE; D3ZSI8; -.
DR UCSC; RGD:1306127; rat.
DR RGD; 1306127; Pip5k1a.
DR VEuPathDB; HostDB:ENSRNOG00000021068; -.
DR eggNOG; KOG0229; Eukaryota.
DR HOGENOM; CLU_004312_5_1_1; -.
DR InParanoid; D3ZSI8; -.
DR OMA; NIRLVAM; -.
DR PhylomeDB; D3ZSI8; -.
DR TreeFam; TF319618; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR PRO; PR:D3ZSI8; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000021068; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; D3ZSI8; RN.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; ISO:RGD.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0090630; P:activation of GTPase activity; ISO:RGD.
DR GO; GO:0060326; P:cell chemotaxis; ISO:RGD.
DR GO; GO:0010761; P:fibroblast migration; ISO:RGD.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:RGD.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISO:RGD.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0008654; P:phospholipid biosynthetic process; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0097178; P:ruffle assembly; ISO:RGD.
DR Gene3D; 3.30.800.10; -; 1.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
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 ATP-binding; Cell membrane; Cell projection; Cytoplasm; Isopeptide bond;
KW Kinase; Lipid metabolism; Membrane; Nucleotide-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..546
FT /note="Phosphatidylinositol 4-phosphate 5-kinase type-1
FT alpha"
FT /id="PRO_0000424437"
FT DOMAIN 65..433
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 441..522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 87
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q99755"
SQ SEQUENCE 546 AA; 60605 MW; F0DF7489A100D9C3 CRC64;
MASASSGPAA AGFSPLDSGV PAGTAASGIK RGTVSEGPYA SLMPVKKIGH RSVDSSGETT
YKKTTSSALK GAIQLGITHT VGSLSTKPER DVLMQDFYVV ESIFFPSEGS NLTPAHHYND
FRFKTYAPVA FRYFRELFGI RPDDYLYSLC SEPLIELSNS GASGSLFYVS SDDEFIIKTV
QHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQAGG KNIRIVVMNN LLPRSVKMHM
KYDLKGSTYK RRASQKEREK TLPTFKDLDF LQDIPDGLFL DADMYSALCK TLQRDCLVLQ
SFKIMDYSLL MSIHNMDHAQ REPMNSETQY SIDTRRPAPQ KALYSTAMES IQGEARRGGT
VETEDHMGGI PARNNKGERL LLYIGIIDIL QSYRFVKKLE HSWKALVHDG DTVSVHRPGF
YAERFQRFMC NTVFKKIPLK PSPTKKFRSG PSFSRRSGPS GNSCTPSQPT ASGEHKAQVT
TKAEVEPDIH LGRPDVLPQT PPLEEISEGS PVPGPSFSPA VGQPLQILNL SSTLEKLDVA
ESELTH
