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Protein

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

Gene

Pip5k1c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth.10 Publications

Catalytic activityi

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

Activity regulationi

Activated by phosphatidic acid.1 Publication

Kineticsi

  1. KM=37 µM for PtdIns4P
  2. KM=39 µM for ATP

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Transferase
    Biological processCell adhesion, Chemotaxis, Endocytosis, Exocytosis, Phagocytosis
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-1660499 Synthesis of PIPs at the plasma membrane
    R-MMU-399955 SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
    R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
    R-MMU-8856828 Clathrin-mediated endocytosis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (EC:2.7.1.68)
    Short name:
    PIP5K1-gamma
    Short name:
    PtdIns(4)P-5-kinase 1 gamma
    Alternative name(s):
    Phosphatidylinositol 4-phosphate 5-kinase type I gamma
    Short name:
    PIP5KIgamma
    Gene namesi
    Name:Pip5k1c
    Synonyms:Kiaa0589
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:1298224 Pip5k1c

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    According to some authors, mutants die within hours after birth and are unable to feed after birth (PubMed:15386003). According to another report, mutants are embryonically lethal at organogenesis stage, and display cardiovascular and neuronal defects (PubMed:15386003). PIP5K1C and PIP5K1B double mutant mice die within minutes after birth. PIP5K1C and PIP5K1A double mutant mice are embryonic lethal. Bone marrow-derived macrophages are defective in phagocytosis, attachment to IgG-opsonized particles and Fc-gamma-R clustering, and display highly polymerized actin cytoskeleton. Neurons display defects in synaptic transmission due to defects in synaptic vesicle trafficking at different levels. T-cells mutant for isoform 1 display increase adhesion and polarization.5 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi253D → A: Abolishes lipid kinase activity. Does not affect targeting of TLN1 to plasma membrane. Affects assembly of TLN1 into focal adhesions. Affects uropodium formation and retraction of the cell rear. 2 Publications1
    Mutagenesisi634Y → F: Cannot rescue the effect PIP5K1C knockdown on EGF-stimulated cell migration. Does not affect lipid kinase activity. Does not alter binding to tailin. Decreased tailin assembly into focal adhesions. Increased interaction with PLCG1. 1 Publication1
    Mutagenesisi635F → A: Abolishes interaction with AP2B1. 1 Publication1
    Mutagenesisi642W → A: Abolishes interaction with AP2B1. 1 Publication1
    Mutagenesisi644Y → F: Loss of phosphorylation by CSK. Abolishes interaction with AP-2 complex. Cannot rescue the effect PIP5K1C knockdown on EGF-stimulated cell migration. 4 Publications1
    Mutagenesisi645S → F: Cannot rescue the effect PIP5K1C knockdown on EGF-stimulated cell migration. Decreased tailin assembly into focal adhesions. 1 Publication1
    Mutagenesisi646P → F: Abolishes interaction with AP-2 complex. 1 Publication1
    Mutagenesisi647L → V: Abolishes interaction with AP-2 complex. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001854631 – 661Phosphatidylinositol 4-phosphate 5-kinase type-1 gammaAdd BLAST661

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei265N6-acetyllysineBy similarity1
    Modified residuei268N6-acetyllysineBy similarity1
    Modified residuei459Asymmetric dimethylarginine; alternateCombined sources1
    Modified residuei459Omega-N-methylarginine; alternateCombined sources1
    Modified residuei554PhosphoserineBy similarity1
    Modified residuei634Phosphotyrosine; by EGFR1 Publication1
    Modified residuei644Phosphotyrosine; by CSK1 Publication1
    Modified residuei645Phosphoserine; by CDK5, MAPK1 and CDK1By similarity1
    Modified residuei655PhosphoserineCombined sources1
    Modified residuei659PhosphoserineBy similarity1
    Modified residuei661PhosphothreonineBy similarity1

    Post-translational modificationi

    Phosphorylation on Ser-645 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-644 is necessary for targeting to focal adhesions. Phosphorylation on Ser-645 and Tyr-644 are mutually exclusive. Phosphorylated by SYK and CSK. Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-634 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-644 enhances binding to tailins (TLN1 and TLN2); others that phosphorylation at Tyr-644 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-645.5 Publications
    Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells (By similarity).By similarity

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein

    Proteomic databases

    MaxQBiO70161
    PaxDbiO70161
    PeptideAtlasiO70161
    PRIDEiO70161

    PTM databases

    iPTMnetiO70161
    PhosphoSitePlusiO70161

    Expressioni

    Tissue specificityi

    High expression in brain. Also detected in lung, thymus, heart, testicle, kidney and embryo. Highly expressed in forebrain, in particular in cerebellum, hippocampus and cerebral cortex.3 Publications

    Developmental stagei

    Expression increases during embryonic development and continued to steadily increase postnatally.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000034902 Expressed in 311 organ(s), highest expression level in cerebellum
    ExpressionAtlasiO70161 baseline and differential
    GenevisibleiO70161 MM

    Interactioni

    Subunit structurei

    Isoform 1 interacts with TLN1. Interacts with TLN2; interaction stimulates lipid kinase activity. May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6 (By similarity). Interacts with AP2B1. Isoform 1 interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C. Interacts with CDH1 (By similarity). Interacts with CSK. Interacts with PLCG1; interaction is abolished upon EGF stimulation. Interacts with LAPTM4B; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C (By similarity).By similarity6 Publications

    Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi202169, 1 interactor
    IntActiO70161, 8 interactors
    MINTiO70161
    STRINGi10090.ENSMUSP00000100964

    Structurei

    Secondary structure

    1661
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO70161
    SMRiO70161
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO70161

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini75 – 443PIPKPROSITE-ProRule annotationAdd BLAST369

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni636 – 661Mediates interaction with TLN2Add BLAST26

    Phylogenomic databases

    eggNOGiKOG0229 Eukaryota
    COG5253 LUCA
    GeneTreeiENSGT00760000119184
    HOGENOMiHOG000193876
    HOVERGENiHBG052818
    InParanoidiO70161
    KOiK00889
    OMAiHYADFRF
    PhylomeDBiO70161
    TreeFamiTF319618

    Family and domain databases

    Gene3Di3.30.800.10, 1 hit
    3.30.810.10, 2 hits
    InterProiView protein in InterPro
    IPR023610 PInositol-4-P-5-kinase
    IPR027483 PInositol-4-P-5-kinase_C
    IPR002498 PInositol-4-P-5-kinase_core
    IPR027484 PInositol-4-P-5-kinase_N
    PANTHERiPTHR23086 PTHR23086, 1 hit
    PfamiView protein in Pfam
    PF01504 PIP5K, 1 hit
    SMARTiView protein in SMART
    SM00330 PIPKc, 1 hit
    PROSITEiView protein in PROSITE
    PS51455 PIPK, 1 hit

    Sequences (3+)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: O70161-1) [UniParc]FASTAAdd to basket
    Also known as: PIPKIgamma661

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MELEVPDEAE SAEAGAVTAE AAWSAESGAA AGMTQKKAGL AEAPLVTGQP
    60 70 80 90 100
    GPGHGKKLGH RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGNLSSKPER
    110 120 130 140 150
    DVLMQDFYVV ESIFFPSEGS NLTPAHHFQD FRFKTYAPVA FRYFRELFGI
    160 170 180 190 200
    RPDDYLYSLC NEPLIELSNP GASGSVFYVT SDDEFIIKTV MHKEAEFLQK
    210 220 230 240 250
    LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN VLPRVVKMHL
    260 270 280 290 300
    KFDLKGSTYK RRASKKEKEK SLPTYKDLDF MQDMPEGLLL DSDTFGALVK
    310 320 330 340 350
    TLQRDCLVLE SFKIMDYSLL LGVHNIDQQE RERQAEGAQS KADEKRPVAQ
    360 370 380 390 400
    KALYSTAMES IQGGAARGEA IETDDTMGGI PAVNGRGERL LLHIGIIDIL
    410 420 430 440 450
    QSYRFIKKLE HTWKALVHDG DTVSVHRPSF YAERFFKFMS STVFRKSSSL
    460 470 480 490 500
    KSSPSKKGRG ALLAVKPLGP TAAFSASQIP SEREDVQYDL RGARSYPTLE
    510 520 530 540 550
    DEGRPDLLPC TPPSFEEATT ASIATTLSST SLSIPERSPS DTSEQPRYRR
    560 570 580 590 600
    RTQSSGQDGR PQEEPHAEDL QKITVQVEPV CGVGVVPKEE GAGVEVPPCG
    610 620 630 640 650
    ASAAASVEID AASQASEPAS QASDEEDAPS TDIYFPTDER SWVYSPLHYS
    660
    ARPASDGESD T
    Length:661
    Mass (Da):72,408
    Last modified:October 25, 2005 - v2
    Checksum:i4A3B71E4465B83C3
    GO
    Isoform 2 (identifier: O70161-2) [UniParc]FASTAAdd to basket
    Also known as: PIPKIgamma627

    The sequence of this isoform differs from the canonical sequence as follows:
         343-402: Missing.
         635-635: F → FFAHGRYWLFSPRRRQLRAVTPNHTGT

    Note: No experimental confirmation available.
    Show »
    Length:627
    Mass (Da):69,199
    Checksum:iC40D860D3F3419BD
    GO
    Isoform 3 (identifier: O70161-3) [UniParc]FASTAAdd to basket
    Also known as: PIPKIgamma635

    The sequence of this isoform differs from the canonical sequence as follows:
         636-661: Missing.

    Show »
    Length:635
    Mass (Da):69,502
    Checksum:i781F012CC868250A
    GO

    Computationally mapped potential isoform sequencesi

    There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    F8WHW6F8WHW6_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    687Annotation score:
    F7C0X9F7C0X9_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    216Annotation score:
    E0CYP4E0CYP4_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    100Annotation score:
    F6SMP3F6SMP3_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    133Annotation score:
    F6TL71F6TL71_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    73Annotation score:
    E0CZ71E0CZ71_MOUSE
    Phosphatidylinositol 4-phosphate 5-...
    Pip5k1c
    61Annotation score:

    Sequence cautioni

    The sequence BAC65601 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti110V → M in BAA25664 (PubMed:9535851).Curated1
    Sequence conflicti122L → F in BAA25664 (PubMed:9535851).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_016013343 – 402Missing in isoform 2. 1 PublicationAdd BLAST60
    Alternative sequenceiVSP_016014635F → FFAHGRYWLFSPRRRQLRAV TPNHTGT in isoform 2. 1 Publication1
    Alternative sequenceiVSP_016015636 – 661Missing in isoform 3. 2 PublicationsAdd BLAST26

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB006916 mRNA Translation: BAA25664.1
    AK122319 mRNA Translation: BAC65601.2 Different initiation.
    AK154816 mRNA Translation: BAE32849.1
    AK171576 mRNA Translation: BAE42536.1
    BC019138 mRNA Translation: AAH19138.1
    BC094665 mRNA Translation: AAH94665.1
    CCDSiCCDS35994.1 [O70161-1]
    CCDS48643.1 [O70161-3]
    RefSeqiNP_001140159.1, NM_001146687.2 [O70161-3]
    NP_001280575.1, NM_001293646.1
    NP_001280576.1, NM_001293647.1
    NP_032870.2, NM_008844.3 [O70161-1]
    UniGeneiMm.24222
    Mm.29836
    Mm.471109

    Genome annotation databases

    EnsembliENSMUST00000105327; ENSMUSP00000100964; ENSMUSG00000034902 [O70161-1]
    ENSMUST00000163075; ENSMUSP00000124155; ENSMUSG00000034902 [O70161-3]
    GeneIDi18717
    KEGGimmu:18717
    UCSCiuc007ghc.3 mouse [O70161-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB006916 mRNA Translation: BAA25664.1
    AK122319 mRNA Translation: BAC65601.2 Different initiation.
    AK154816 mRNA Translation: BAE32849.1
    AK171576 mRNA Translation: BAE42536.1
    BC019138 mRNA Translation: AAH19138.1
    BC094665 mRNA Translation: AAH94665.1
    CCDSiCCDS35994.1 [O70161-1]
    CCDS48643.1 [O70161-3]
    RefSeqiNP_001140159.1, NM_001146687.2 [O70161-3]
    NP_001280575.1, NM_001293646.1
    NP_001280576.1, NM_001293647.1
    NP_032870.2, NM_008844.3 [O70161-1]
    UniGeneiMm.24222
    Mm.29836
    Mm.471109

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Y19X-ray2.60A/C/E/G/I/K638-651[»]
    2H7DNMR-B643-652[»]
    2H7ENMR-B643-652[»]
    ProteinModelPortaliO70161
    SMRiO70161
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi202169, 1 interactor
    IntActiO70161, 8 interactors
    MINTiO70161
    STRINGi10090.ENSMUSP00000100964

    PTM databases

    iPTMnetiO70161
    PhosphoSitePlusiO70161

    Proteomic databases

    MaxQBiO70161
    PaxDbiO70161
    PeptideAtlasiO70161
    PRIDEiO70161

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000105327; ENSMUSP00000100964; ENSMUSG00000034902 [O70161-1]
    ENSMUST00000163075; ENSMUSP00000124155; ENSMUSG00000034902 [O70161-3]
    GeneIDi18717
    KEGGimmu:18717
    UCSCiuc007ghc.3 mouse [O70161-1]

    Organism-specific databases

    CTDi23396
    MGIiMGI:1298224 Pip5k1c
    RougeiSearch...

    Phylogenomic databases

    eggNOGiKOG0229 Eukaryota
    COG5253 LUCA
    GeneTreeiENSGT00760000119184
    HOGENOMiHOG000193876
    HOVERGENiHBG052818
    InParanoidiO70161
    KOiK00889
    OMAiHYADFRF
    PhylomeDBiO70161
    TreeFamiTF319618

    Enzyme and pathway databases

    ReactomeiR-MMU-1660499 Synthesis of PIPs at the plasma membrane
    R-MMU-399955 SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
    R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
    R-MMU-8856828 Clathrin-mediated endocytosis

    Miscellaneous databases

    ChiTaRSiPip5k1c mouse
    EvolutionaryTraceiO70161
    PROiPR:O70161
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000034902 Expressed in 311 organ(s), highest expression level in cerebellum
    ExpressionAtlasiO70161 baseline and differential
    GenevisibleiO70161 MM

    Family and domain databases

    Gene3Di3.30.800.10, 1 hit
    3.30.810.10, 2 hits
    InterProiView protein in InterPro
    IPR023610 PInositol-4-P-5-kinase
    IPR027483 PInositol-4-P-5-kinase_C
    IPR002498 PInositol-4-P-5-kinase_core
    IPR027484 PInositol-4-P-5-kinase_N
    PANTHERiPTHR23086 PTHR23086, 1 hit
    PfamiView protein in Pfam
    PF01504 PIP5K, 1 hit
    SMARTiView protein in SMART
    SM00330 PIPKc, 1 hit
    PROSITEiView protein in PROSITE
    PS51455 PIPK, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPI51C_MOUSE
    AccessioniPrimary (citable) accession number: O70161
    Secondary accession number(s): Q505A1, Q80TW9, Q8VCU5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
    Last sequence update: October 25, 2005
    Last modified: November 7, 2018
    This is version 145 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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