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FLASH GENE
Symbol TPCN1 contributors: mct/npt - updated : 27-12-2017
HGNC name two pore segment channel 1
HGNC id 18182
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two domains conserved positively charged voltage sensor segments
  • six transmembrane segments in S4
    • HOMOLOGY
    interspecies ortholog to murine Tpcn1 (87 pc)
    Homologene
    FAMILY
  • calcium channel alpha-1 subunit family
  • superfamily of voltage-gated ion channel
    • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text intracellularly on endolysosomes (Calcraft 2009)
    basic FUNCTION
  • potentially involved in cell signaling and communication
  • may mediate NAADP-induced Ca2+ release from distinct subsets of acidic organelles, such as the distinguished endosome populations suggested by their subcellular distributions (Calcraft 2009)
  • TPCN1, TPCN2, do not contribute directly to NAADP-induced endolysosomal Ca2+ release
  • is a member of a new family of voltage-gated Na(+) channels that senses pH changes and confers electrical excitability to organelles
  • TPCN1 and TPCN2 have important but distinct roles in the endo-lysosomal pathway
  • is a central component of cytokinetic control, specifically during abscission, suggesting a means by which the endolysosomal system may play an active role in this process
  • TPCN1, whose expression tended to increase in TPCN2 null islets, might be sufficient to support normal Ca(2+) dynamics in response to stimulation by nutrients or incretins
  • endolysosomal channels TPCN1 and TPCN2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts
  • significantly different gating and ion conducting properties of TPCN1 and TPCN2 suggest that these two ion channels may play complementary physiological roles as Ca(2+) -release channels of the endolysosomal system
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MCOLN1 and TPCN1 are present in the same complex, they function as two independent organellar ion channels and TPCN1, but not MCOLN1 are the targets for NAADP
  • molecular interaction between human TPCN1/TPCN2 and the anti-apoptotic protein HAX1 (HCLS-associated X-1)and the observed binding of HAX1 to TPCs may represent a conserved mechanism by which these endolysosomal ion channels are regulated
  • TPCN1, TPCN2 mediate Ca(2+) signals through the Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) to control a range of Ca(2+)-dependent event
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • absence of intracellular ion channels Tpcn1 and Tpcn2 leads to mature-onset obesity in male mice, due to impaired lipid availability for thermogenesis in brown adipose tissue