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FLASH GENE
Symbol PIP5K1C contributors: mct/npt - updated : 05-09-2023
HGNC name phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
HGNC id 8996
Corresponding disease
DIDMSO intellectual disability, developmental delay, microcephaly, seizures, ocular abnormalities
LCCS3 lethal congenital contracture syndrome 3
Location 19p13.3      Physical location : 3.630.181 - 3.700.445
Synonym name
  • PtdIns(4)P-5-kinase
  • diphosphoinositide kinase
    • Synonym symbol(s) KIAA0589, LCCS3, PIP5K-GAMMA, PIP5Kgamma
    EC.number 2.7.1.37, 2.7.1.68
    DNA
    TYPE functioning gene
    STRUCTURE 70.30 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    MAPPING cloned Y linked N status provisional
    Map pter - D19S886 - ELA2 - D19S878 - PIP5K1C - FUT3 - D19S216 - EMR1 - D19S912 - RPS28 - D19S413 - cen
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    text with two alternatively spliced forms, 87kDa, 90kDa (Ishihara)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 4998 87 640 - 2009 19548880
  • PIPKIgamma640 or PIPKIgamma87, PIP5KIC_v2
    • 18 - 5082 90 668 highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals 2009 19548880
  • PIPKIgamma668 or PIPKIgamma90, PIP5KIC_v1
  • negative regulator of Ag-induced T cell adhesion and activation
  • associates with both the mu and beta2 subunits of AP-2 via multiple sites
  • only p90, a longer splice form of platelet-specific PIP5KC1, but not the shorter p87 PIP5KC1, regulates the ligand-binding activity of integrins via talin (PMID: 23372168)
    • 18 - 3326 - 700 present in the nucleus 2009 19548880
  • C-terminal splice variants of PIPKIgamma
    • 18 - 2933 - 707 targeted to intracellular vesicle-like structures, where it co-localizes with markers of several types of endosomal compartments 2014 24610942
  • PIP5K1gamma_v5
  • associates with E-cadherin and promotes its lysosomal degradation
  • with SNX5 are crucial regulators of E-cadherin sorting and degradation
  • with SNX5 form a signaling nexus that controls EGFR endosomal sorting, degradation, and signaling (PMID: 23602387)
    • 18 - - - - specifically in brain 2011 21756881
  • PIP5K1gamma93
  • alternative splicing site 78 nucleotides from the start of exon 16c
    • 18 - - - - apparently widespread in its distribution 2011 21756881
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrain   highly Homo sapiens
     gangliasensory gangliadorsal root highly Homo sapiens
    Respiratorylung   highly
    Urinarykidney   highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral  highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • localized in a ring-like pattern in the intermediate pericentriolar materials around the proximal end of the centriole in G1, S and G2 phases, but not in M phase
    • basic FUNCTION
  • implicated in the synthesis of a PI(4,5)P(2) pool that acts as a positive regulator of clathrin coat recruitment and actin function at the synapse
  • required for actin organization and fascia adhesion formation in myocardiocytes
  • novel component of the backness signal that regulates rear retraction during chemotaxis
  • playing a role in cell migration and the requirement of cell migration in neural tube closure
  • multiple interactions between PIPK5K1C and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated synaptic vesicle endocytosis
  • involved in the regulation of actin reorganization and focal adhesion dynamics, which are critical in cell migration and neurite outgrowth
  • PIP5K1C regulated the adhesion through facilitating RhoA GTPase and integrin activation by chemoattractants
  • also participates in cytoskeletal organization by delivering talin to integrins, thereby enhancing their ligand binding capacity
  • exerts varied effects on osteoclasts
  • optimal amounts of PIP5K1C and its metabolites are essential for skeletal homeostasis
  • although it is essential for normal platelet function, individual isoforms of PIP5KIC fulfill unique roles for the integrin-dependent integrity of the membrane cytoskeleton and for the stabilization of platelet adhesion
  • plays an important role in centriole fidelity
  • negative regulator of centriole duplication, which acts by modulating the homeostasis of PLK4 activity
  • regulates PIP2-dependent nociceptive signaling, suggesting that PIP5K1C is a therapeutic target for chronic pain
  • lipid kinase that plays a pivotal role in the regulation of receptor-mediated calcium signaling in multiple tissues
  • function of PIP5K1C in the control of bone mass
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with EZH2 (EZH2 negatively regulates intracellular Ca2+ through suppression of PIP5K1C)
  • directly associates with beta-catenin and increases beta-catenin activity downstream of growth factor stimulation
  • PIP5K1C associates with the exocyst via a direct interaction with EXOC7, the exocyst subunit that guides the polarized targeting of exocyst to the plasma membrane
  • promotes osteoclast differentiation by sensitizing its precursors to TNFSF11
  • is likely to function at the PLK4 level to restrain centriole duplication
  • PDZD7 long isoform-specific binding partner PIP5K1C, which has been shown to play important roles in hearing and might participate in the function and/or transportation of PDZD7
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) LCCS3 , DIDMSO
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    obesity  
    could be a novel potential target for regulating fat accumulation, which could provide novel insight into the treatment of obesity
    osteoarticularboneostéoporosis
    potential therapeutic target for osteoporosis
    ANIMAL & CELL MODELS
  • PIP5KI-null embryos have myocardial developmental defects associated with impaired intracellular junctions that lead to heart failure and extensive prenatal lethality
  • PIP5KIC-/- mice have arrested osteoclastogenesis
  • PIP5K1c deficiency in adipocytes decreased adipocyte volume in HFD-induced obese mice, whereas no significant differences were observed in body weight and adipose tissue weight under normal chow diet conditions
  • Pip5k1c-/- mice exhibit major neurological and/or behavioral defects associated with early postnatal lethality resulting from impaired synaptic vesicle trafficking