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Symbol TPCN2 contributors: shn/mct - updated : 27-12-2017
HGNC name two pore segment channel 2
HGNC id 20820
Location 11q13.3      Physical location : 68.816.349 - 68.858.072
Synonym name
  • two pore calcium channel protein 2
  • voltage-dependent calcium channel protein TPC2
  • Synonym symbol(s) TPC2, FLJ41094, SHEP10
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 41.70 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D11S4178 - D11S4113 - TPCN2 - D11S4095 - D11S4136 - qter
    Physical map
    LOC132740 11q13.1 similar to unc-93 homolog B1; unc93 (C.elegans) homolog B; unc-93 related protein LOC390215 11 similar to seven transmembrane helix receptor OR7E11P 11q11 olfactory receptor, family 7, subfamily E, member 11 pseudogene LOC390216 11 similar to mannosyltransferase LOC158490 11q13.1 similar to hypothetical protein FLJ10661 LOC387785 11 LOC387785 LOC390217 11 similar to chromosome 11 open reading frame2; chromosome  11 open reading frame2 LOC341128 11q13.1 similar to seven transmembrane helix receptor UNC93B1 11q13 unc-93 homolog B1 (C. elegans) ALDH3B1 11q13 aldehyde dehydrogenase 3 family, member B1 NDUFS8 11q13 NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) TCIRG1 11q13.4-q13.5 T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein a isoform 3 CHK 11q13.1 choline kinase CGI-85 11q13 choline kinase C11orf24 11q13 chromosome 11 open reading frame 24 LRP5 11q13 low density lipoprotein receptor-related protein 5 C11orf23 11q13 chromosome 11 open reading frame 23 GAL 11q13.3-q13.5 galanin MTL5 11q13.2-q13.3 metallothionein-like 5, testis-specific (tesmin) CPT1A 11q13.1-q13.2 carnitine palmitoyltransferase 1A (liver) MRPL21 11q13.1 mitochondrial ribosomal protein L21 IGHMBP2 11q13.2-q13.4 immunoglobulin mu binding protein 2 MRGD 11 mas-related G protein-coupled MRGD MGC21621 11q13.1 G protein-coupled receptor MrgF TPCN2 11q13.1 two pore segment channel 2 LOC338694 11q13.2 hypothetical protein LOC338694 MYEOV 11q13.1 myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) LOC390218 11 similar to Interferon-induced transmembrane protein 3 (Interferon-inducible protein 1-8U) LOC220061 11q13.2 similar to proline rich antigen 2 CCND1 11q13.3 cyclin D1 (PRAD1: parathyroid adenomatosis 1) ORAOV1 11q13 oral cancer overexpressed 1 FGF19 11q13.1 fibroblast growth factor 19 FGF4 11q13.3 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene) FGF3 11q13.3 fibroblast growth factor 3 (murine mammary tumor virus integration site (v-int-2) oncogene homolog) ORAOV2 11q13.2 oral cancer overexpressed 2
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 5026 - 752 - 2016 27140606
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Urinarykidney   highly
    Visualeye   highly
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoclast Homo sapiensFetal
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
  • two repeats of a six-transmembrane-domain
  • a putative pore region crucial for conferring Ca2+ selectivity
    interspecies ortholog to Tpcn2, Rattus norvegicus
    ortholog to Tpcn2, Mus musculus
    ortholog to TPCN2, Pan troglodytes
    ortholog to zgc:152898, Danio rerio
  • two-pore channels
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     intracellular
  • 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
    a component
  • is a component of the platelet dense granules (PDGs) membrane that regulates PDG luminal pH and the pool of releasable Ca(2+)
    small molecule
  • 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
    Other a highly selective Ca(2+) channel that is regulated by intralysosomal pH
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in oral cancer
    Variant & Polymorphism SNP skin and hair pigmentation
    Candidate gene
    Therapy target
  • 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