Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TPCN2 contributors: shn/mct - updated : 27-12-2017
HGNC name two pore segment channel 2
HGNC id 20820
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
25 - 5026 - 752 - 2016 27140606
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly
Urinarykidney   highly
Visualeye   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Skeletonosteoclast Homo sapiensFetal
Skin/Tegumentmelanocyte Homo sapiens
cell lineage
cell lines
fluid/secretion blood
at STAGE
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