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FLASH GENE
Symbol TPCN2 contributors: shn/mct - updated : 27-12-2017
HGNC name two pore segment channel 2
HGNC id 20820
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two repeats of a six-transmembrane-domain
  • a putative pore region crucial for conferring Ca2+ selectivity
  • HOMOLOGY
    interspecies ortholog to Tpcn2, Rattus norvegicus
    ortholog to Tpcn2, Mus musculus
    ortholog to TPCN2, Pan troglodytes
    ortholog to zgc:152898, Danio rerio
    Homologene
    FAMILY
  • two-pore channels
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • specifically targeted to lysosomal membranes
  • localizes to the melanosome-limiting membrane
  • basic FUNCTION
  • displays the basic properties of native NAADP-dependent Ca(2+)-release channels
  • is a regulator of pigmentation
  • major component of the long-sought lysosomal NAADP-dependent Ca(2+)-release channel
  • lysosomal Ca2+ release channel targeted by NAADP
  • a highly selective Ca2+ channel
  • exhibits many unique functional characteristics that can explain the idiosyncrasies of cellular NAADP signaling characteristics
  • functional ion channel activated by NAADP (Nicotinic acid adenine dinucleotide phosphate)
  • behaves as a functional ion channel and, crucially, possesses the conduction properties required of an intracellular Ca2+ release channel, and operating as a dual sensor of luminal pH and Ca2+
  • is a novel critical molecule for osteoclastogenesis
  • is a highly Na+-selective channel in the endolysosome
  • TPCN1, TPCN2, do not contribute directly to NAADP-induced endolysosomal Ca2+ release
  • TPCN1 and TPCN2 have important but distinct roles in the endo-lysosomal pathway
  • TPCN2 impacts mammalian target of rapamycin reactivation during the process of autophagy and contributes to maintenance of muscle homeostasis
  • 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
  • is not absolutely required for normal glucose- or incretin-stimulated insulin secretion from the beta-cell
  • 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
  • regulates pigmentation through two fundamental determinants of melanosome function: pH and size
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • is a component of the platelet dense granules (PDGs) membrane that regulates PDG luminal pH and the pool of releasable Ca(2+)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • localized Ca2+ release via TPCN2 might trigger the generation of more global Ca2+ release from the sarcoplasmic reticulum (SR) via Ca2+-induced Ca2+ release
  • cell & other
    REGULATION
    Other a highly selective Ca(2+) channel that is regulated by intralysosomal pH
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in oral cancer
    Susceptibility
    Variant & Polymorphism SNP skin and hair pigmentation
    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