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UniProtKB - O70161 (PI51C_MOUSE)

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Protein

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

Gene

Pip5k1c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 have 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.

Enzyme regulationi

Activated by phosphatidic acid.1 Publication

Kineticsi

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

    GO - Molecular functioni

    • 1-phosphatidylinositol-4-phosphate 5-kinase activity Source: MGI
    • ATP binding Source: UniProtKB-KW
    • talin binding Source: MGI
    Complete GO annotation...

    GO - Biological processi

    • axonogenesis Source: MGI
    • chemotaxis Source: UniProtKB-KW
    • cytoskeletal anchoring at plasma membrane Source: MGI
    • exocytosis Source: UniProtKB-KW
    • phagocytosis Source: UniProtKB-KW
    • phosphatidylinositol biosynthetic process Source: MGI
    • phosphatidylinositol metabolic process Source: MGI
    • platelet aggregation Source: MGI
    Complete GO annotation...

    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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
    Proteomesi
    • UP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:1298224. Pip5k1c.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: MGI
    • endomembrane system Source: UniProtKB-SubCell
    • focal adhesion Source: UniProtKB-SubCell
    • nucleoplasm Source: MGI
    • phagocytic cup Source: UniProtKB-SubCell
    • ruffle membrane Source: UniProtKB-SubCell
    • uropod Source: UniProtKB-SubCell
    Complete GO annotation...

    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.
    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.By similarity6 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • talin binding Source: MGI
    Complete GO annotation...

    Protein-protein interaction databases

    BioGridi202169. 1 interactor.
    IntActiO70161. 8 interactors.
    MINTiMINT-4105231.
    STRINGi10090.ENSMUSP00000100964.

    Structurei

    Secondary structure

    1661
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi642 – 644Combined sources3
    Helixi646 – 648Combined sources3

    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...

    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.
    PhylomeDBiO70161.
    TreeFamiTF319618.

    Family and domain databases

    Gene3Di3.30.800.10. 1 hit.
    3.30.810.10. 1 hit.
    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

    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

    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

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

    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: May 10, 2017
    This is version 139 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