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Symbol TRPV5 contributors: mct/pgu - updated : 24-06-2015
HGNC name transient receptor potential cation channel, subfamily V, member 5
HGNC id 3145
Location 7q34      Physical location : 142.605.647 - 142.630.820
Synonym name
  • epithelium calcium channel 1
  • osm-9-like TRP channel 3
  • calcium transporter protein 2
  • Synonym symbol(s) CAT2, ECAC1, OTRPC3, ECaC
    TYPE functioning gene
    STRUCTURE 25.17 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure four putative vitamin D(3)-responsive elements
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2486 - 729 - 2009 19157541
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland    
    Hearing/Equilibriumearinner    Homo sapiens
    Lymphoid/Immunelymph node    
    Urinarykidneytubulecollecting duct highly Homo sapiens
     kidneytubuleconvoluted tubuledistal tubulehighly Homo sapiens
    Visualeye     Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • three N terminal ankyrin (ANK) repeats, implicated in channel assembly
  • N linked glycosylation sites
  • six transmembrane-spanning domains with a putative pore-forming region between transmembrane domains 5 and 6
  • multiple potential phosphorylation sites
  • a C terminal cytoplasmic domain, with two Ca2+-sensing stretches, playing a central role in TRPV5 channel regulation, and involved in Ca2+-dependent inactivation (essential role for residue His712 in TRPV5 plasma membrane trafficking)
    interspecies homolog to rabbit Ecac
    intraspecies homolog to TRPV6
  • transient receptor family
  • mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels
  • CATEGORY receptor , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
  • colocalized with S100A10 and ANX2 along the apical domain of kidney distal tubular cells
  • with CASR, co-localize at the luminal membrane of distal convoluted tubules (DCT) and connecting tubules (CNT)in the kidney
  • localized to the apical membrane of distal convoluted tubules and connecting tubules
  • increased plasma membrane expression of TRPV5 was likely due to the enhanced delivery of mature TRPV5 to the plasma membrane from its intracellular pool via the secretory pathway
  • KL and sialidase stabilize TRPV5 on the plasma membrane
  • basic FUNCTION
  • Ca2+ selective channel, exhibiting Ca2+ dependent autoregulatory mechanisms including fast inactivation and slow down regulation
  • having a critical role in regulating lung inflammatory responses, via regulation of dendritic cell activation and subsequent T cell responses
  • playing an essential role in transcellular Ca2+ transport and being one of the most Ca2+-selective members of the transient receptor potential superfamily
  • constitutively internalized via a dynamin and clathrin-dependent mechanism, enters the recycling pathway (the recycling rate of TRPV5 is modulated by the intracellular Ca2+ concentration)
  • epithelial calcium channels that mediate apical calcium entry in the transcellular calcium transport pathway
  • constitutes the luminal gate for Ca(2+) entry in the distal convoluted tubule and has several putative PKA phosphorylation sites
  • functions as a gatekeeper for transcellular Ca2+ reabsorption in the kidney
  • could function in retinal pigment epithelium to mediate calcium influx from subretinal space and thus regulate changes in subretinal space calcium composition that accompany light/dark transitions
  • constitutes the apical entry gate for Ca(2+) transport in renal epithelial cells
  • plays a crucial role in epithelial calcium transport in the kidney
  • TRPV5 and TRPV6 are crucial gates controlling cadmium and zinc levels in the human body especially under low calcium dietary conditions, when these channels are maximally upregulated
  • facilitates Ca2+ reabsorption in the kidney and is regulated by sialidase and the hormone KL
  • facilitates transcellular Ca2+ transport in the distal convoluted tubule (DCT) of the kidney
  • is one of the two channels in the TRPV family that exhibit high selectivity to Ca(2+) ions
  • mediates Ca(2+) influx into cells as the first step to transport Ca(2+) across epithelia
  • possible role of TRPV5 in hypercalciuric disorders in humans
  • active Ca(2+) reabsorption in the late distal convoluted and connecting tubules (DCT2/CNT) is initiated by Ca(2+) influx through the transient receptor potential vanilloid type 5 (TRPV5) Ca(2+) channel
  • TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues
    PHYSIOLOGICAL PROCESS active transport
    text transcellular calcium transport
    a component
  • homotetramer and probably heterotetramer with TRPV6
  • MCOLN3 and TRPV5 associate to form a novel heteromeric ion channel
    small molecule metal binding, nucleotide,
  • Mg2+
  • ATP
  • protein
  • colocalizing with calbindin
  • S100A10 and probably with the ANAX2-S100A10 heterotetramer
  • interacting with WNK4 and TRPV6 (WNK4 increases the complexly glycosylated TRPV5, which is likely on its way to the plasma membrane through the secretory pathway)
  • interacting with WNK4 (decreases cell-surface abundance of TRPV5 by enhancing its endocytosis)
  • interacting with SLC9A3R2 (SLC9A3R2 stabilized TRPV5 at the plasma membrane without interrupting the forward trafficking of TRPV5, thus prevented the decline of functional TRPV5 channel caused by WNK4 at later stage)
  • calmodulin negatively modulates TRPV5 activity, which is reversed by PTH-mediated channel phosphorylation (
  • MCOLN3 and TRPV5 associate to form a novel heteromeric ion channel
  • KL and sialidase regulate TRPV5 membrane stabilization in a different manner
  • sialidase, in contrast to klotho, stimulates TRPV5 via a mechanism that is independent of the N-glycan of TRPV5
  • apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor-KL complex and activates a signaling cascade
  • cell & other
    activated by PTH (activates TRPV5 via PKA-dependent phosphorylation)
    CASR (activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5)
    complexly glycosylated TRPV5 that appears at the plasma membrane was increased by WNK3
    UMOD that upregulates TRPV5 by acting from extracellular and by decreasing endocytosis of TRPV5 and the stimulation of Ca(2+) reabsorption via TRPV5 by UMOD may contribute to protection against kidney-stone formation
    Other regulated by cytosolic calcium Ca2+
    modulated by Mg2+
    regulated by STX6 (likely scenario is that most of the core-glycosylated TRPV5 and TRPV6 are trapped in the ER or Golgi complex without reaching the cisternae for complex glycosylation in the presence of excessive syntaxin 6)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    leading to baseline infammation in the lung
    Variant & Polymorphism
    Candidate gene
    Therapy target
    TRPV5 represents a potential therapeutic target for disorders with altered Ca(2+) homeostasis