PI51C_RAT
ID PI51C_RAT Reviewed; 688 AA.
AC Q5I6B8;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma {ECO:0000250|UniProtKB:O60331};
DE Short=PIP5K1-gamma {ECO:0000250|UniProtKB:O60331};
DE Short=PtdIns(4)P-5-kinase 1 gamma {ECO:0000250|UniProtKB:O60331};
DE EC=2.7.1.68 {ECO:0000250|UniProtKB:O60331};
DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I gamma {ECO:0000250|UniProtKB:O60331};
DE Short=PIP5KIgamma {ECO:0000250|UniProtKB:O60331};
GN Name=Pip5k1c {ECO:0000312|RGD:1309938};
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 [MRNA], MUTAGENESIS OF LYS-188 AND ASP-316, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Hippocampus;
RX PubMed=14741049; DOI=10.1042/bj20031394;
RA Giudici M.-L., Emson P.C., Irvine R.F.;
RT "A novel neuronal-specific splice variant of Type I phosphatidylinositol 4-
RT phosphate 5-kinase isoform gamma.";
RL Biochem. J. 379:489-496(2004).
RN [2]
RP FUNCTION, INTERACTION WITH ARF6, AND SUBCELLULAR LOCATION.
RX PubMed=12847086; DOI=10.1083/jcb.200301006;
RA Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V.;
RT "ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by
RT activating phosphatidylinositol phosphate kinase type Igamma.";
RL J. Cell Biol. 162:113-124(2003).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554; SER-682; SER-686 AND
RP THR-688, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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).
CC Together with PIP5K1A, is required for phagocytosis, both enzymes
CC regulating different types of actin remodeling at sequential steps (By
CC similarity). Promotes particle attachment by generating the pool of
CC PtdIns(4,5)P2 that induces controlled actin depolymerization to
CC facilitate Fc-gamma-R clustering. Mediates RAC1-dependent
CC reorganization of actin filaments (By similarity). Required for
CC synaptic vesicle transport (By similarity). Controls the plasma
CC membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle
CC endocytosis and exocytosis. Plays a role in endocytosis mediated by
CC clathrin and AP-2 (adaptor protein complex 2) (PubMed:12847086).
CC Required for clathrin-coated pits assembly at the synapse
CC (PubMed:12847086). Participates in cell junction assembly. Modulates
CC adherens junctions formation by facilitating CDH1/cadherin trafficking.
CC Required for focal adhesion dynamics. Modulates the targeting of talins
CC (TLN1 and TLN2) to the plasma membrane and their efficient assembly
CC into focal adhesions. Regulates the interaction between talins (TLN1
CC and TLN2) and beta-integrins (By similarity). Required for uropodium
CC formation and retraction of the cell rear during directed migration.
CC Has a role in growth factor-stimulated directional cell migration and
CC adhesion (By similarity). Required for talin assembly into nascent
CC adhesions forming at the leading edge toward the direction of the
CC growth factor (By similarity). Negative regulator of T-cell activation
CC and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1)
CC polarization and adhesion induced by T-cell receptor. Together with
CC PIP5K1A has a role during embryogenesis and together with PIP5K1B may
CC have a role immediately after birth (By similarity).
CC {ECO:0000250|UniProtKB:O60331, ECO:0000250|UniProtKB:O70161,
CC ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:12847086}.
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14426;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40364;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40368;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40380;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40384;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40376;
CC Evidence={ECO:0000250|UniProtKB:O60331};
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:O60331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40388;
CC Evidence={ECO:0000250|UniProtKB:O60331};
CC -!- SUBUNIT: Interacts with TLN1 (By similarity). Interacts with TLN2;
CC interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase
CC activity (By similarity). May compete with beta-integrins for the same
CC binding site on TLN1 and TLN2 (By similarity). Interacts with ARF6;
CC interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase
CC activity (PubMed:12847086). Interacts with AP2B1 (By similarity).
CC Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the
CC interaction; clathrin competes with PIP5K1C (By similarity). Interacts
CC with CDH1 (By similarity). Interacts with CSK (By similarity).
CC Interacts with PLCG1; interaction is abolished upon EGF stimulation (By
CC similarity). Interacts with LAPTM4B; promotes SNX5 association with
CC LAPTM4B; kinase activity of PIP5K1C is required; interaction is
CC regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O60331,
CC ECO:0000250|UniProtKB:O70161, ECO:0000269|PubMed:12847086}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12847086};
CC Peripheral membrane protein {ECO:0000269|PubMed:12847086}; Cytoplasmic
CC side {ECO:0000269|PubMed:12847086}. Endomembrane system
CC {ECO:0000269|PubMed:12847086}. Cytoplasm
CC {ECO:0000250|UniProtKB:O70161}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:O60331}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:O60331}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:12847086}. Cell projection, phagocytic cup
CC {ECO:0000250|UniProtKB:O70161}. Cell projection, uropodium
CC {ECO:0000250|UniProtKB:O70161}.
CC -!- PTM: Phosphorylation on Ser-672 negatively regulates binding to TLN2
CC and is strongly stimulated in mitosis. Phosphorylation on Tyr-671 is
CC necessary for targeting to focal adhesions. Phosphorylation on Ser-672
CC and Tyr-671 are mutually exclusive. Phosphorylated by SYK and CSK.
CC Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated
CC at Tyr-635 upon EGF stimulation. Some studies suggest that
CC phosphorylation on Tyr-671 enhances binding to tailins (TLN1 and TLN2)
CC (By similarity); others that phosphorylation at Tyr-671 does not
CC directly enhance binding to tailins (TLN1 and TLN2) but may act
CC indirectly by inhibiting phosphorylation at Ser-672. {ECO:0000250}.
CC -!- PTM: Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase
CC activity. Deacetylation of these sites by SIRT1 positively regulates
CC the exocytosis of TSH-containing granules from pituitary cells (By
CC similarity). {ECO:0000250}.
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DR EMBL; AY850259; AAW34235.1; -; mRNA.
DR RefSeq; NP_001009967.2; NM_001009967.2.
DR RefSeq; NP_001029142.1; NM_001033970.1.
DR AlphaFoldDB; Q5I6B8; -.
DR SMR; Q5I6B8; -.
DR BioGRID; 260791; 2.
DR STRING; 10116.ENSRNOP00000057873; -.
DR iPTMnet; Q5I6B8; -.
DR PhosphoSitePlus; Q5I6B8; -.
DR SwissPalm; Q5I6B8; -.
DR PaxDb; Q5I6B8; -.
DR PRIDE; Q5I6B8; -.
DR GeneID; 314641; -.
DR KEGG; rno:314641; -.
DR UCSC; RGD:1309938; rat.
DR CTD; 23396; -.
DR RGD; 1309938; Pip5k1c.
DR eggNOG; KOG0229; Eukaryota.
DR InParanoid; Q5I6B8; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; Q5I6B8; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:Q5I6B8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0098835; C:presynaptic endocytic zone membrane; IDA:SynGO.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; IEA:UniProtKB-SubCell.
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:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0070527; P:platelet aggregation; ISO:RGD.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:RGD.
DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; 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 Acetylation; ATP-binding; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Chemotaxis; Cytoplasm; Endocytosis; Exocytosis; Kinase;
KW Lipid metabolism; Membrane; Methylation; Nucleotide-binding; Phagocytosis;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..688
FT /note="Phosphatidylinositol 4-phosphate 5-kinase type-1
FT gamma"
FT /id="PRO_0000185464"
FT DOMAIN 75..443
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 48..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 525..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..565
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..628
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 265
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O60331"
FT MOD_RES 268
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O60331"
FT MOD_RES 459
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 459
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 635
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 671
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:O60331"
FT MOD_RES 672
FT /note="Phosphoserine; by CDK5, MAPK1 and CDK1"
FT /evidence="ECO:0000250|UniProtKB:O60331"
FT MOD_RES 682
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 686
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 688
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 188
FT /note="K->A: Reduces activity by over 99%."
FT /evidence="ECO:0000269|PubMed:14741049"
FT MUTAGEN 316
FT /note="D->K: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:14741049"
SQ SEQUENCE 688 AA; 75594 MW; F34E175EFFF54D5D CRC64;
MELEVPDEAE SAEAGAVTAE AAWSAESGAA AGMTQKKAIL AEAPLVTGQP GPGHGKKLGH
RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGNLSSKPER DVLMQDFYVV ESIFFPSEGS
NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSVFYVT
SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN
VLPRVVKMHL KFDLKGSTYK RRASKKEKEK SLPTYKDLDF MQDMPEGLLL DSDTFGALVK
TLQRDCLVLE SFKIMDYSLL LGVHNIDQQE RERQAEGAQS KADEKRPVAQ KALYSTARES
IQGGAARGEA IETDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG
DTVSVHRPSF YAERFFKFMS STVFRKSSSL KSSPSKKGRG ALLAVKPLGP TAAFSASQIP
SEREDVQYDL RGARSYPTLE DEGRPDLLPC TPPSFEEATT ASIATTLSST SLSIPERSPS
DTSEQPRYRR RTQSSGQDGR PQEELHAEDL QKITVQVEPV CGVGVVVPKE QGAGVEVPPS
GASAAATVEV DAASQASEPA SQASDEEDAP STDIYFFAHG RYWLFSPRRR RLRAVTPSHT
GAPTDGRSWV YSPLHYSARP ASDGESDT
