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Symbol TRPV6 contributors: mct/npt - updated : 17-01-2020
HGNC name transient receptor potential cation channel, subfamily V, member 6
HGNC id 14006
  • cytoplasmic N terminus, with a region of amino acids 1-191 interacting with PTPN1 (Sternfeld 2007), extended N terminus
  • three ankyrin repeats multiple phosphrylation sites
  • six transmembrane spanning ankyrin repeats domains, six ankyrin-like repeats in the TRPV6 N-terminal
  • a putative pore-forming region between transmembrane domains 5 and 6
  • a C terminal cytoplasmic domain, with PDZ (Post-synaptic density-95, Drosophila discs-large protein, Zonula occludens protein 1) binding motif
    interspecies homolog to murine Trpv6
    intraspecies homolog to TRPV5
  • transient receptor family
  • TrpV subfamily
  • CATEGORY receptor , transport channel
        plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • most of TRPV6 reside in the ER or Golgi complex after biosynthesis without going through a secretory pathway via trans-Golgi network to reach the plasma membrane
  • TRPC1 is able to suppress TRPV6 dependent currents/entry because of a reduction of TRPV6 plasma membrane expression
  • basic FUNCTION
  • playing a role in 1,25(OH)(2)D(3)-stimulated Ca(2+) reabsorption in the kidney
  • increasing the rate of Ca(2+) dependent cell proliferation which is a prerequisite for its potential role in tumor progression
  • play a role in the intestinal Ca2+ absorption from food, and in the Ca2+ uptake by the epididymal epithelium
  • being a prerequisite for keratinocyte entry into differentiation
  • duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced
  • may participate in Ca2+ transport and/or Ca2+ signaling processes
  • exhibited a lower efficiency of membrane expression and the majority of channel proteins in the plasma membrane were in core-glycosylated form
  • important function of TRPV6 is the Ca2+ uptake in the small intestine, kidney, and bone
  • not required for vitamin D-induced intestinal calcium absorption and may not carry out a significant role in this process (Kutuzova 2008)
  • 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
  • calcium supply is limited and in this condition indirectly regulates bone formation and/or mineralization
  • mediates the first step of transcellular Ca2+ transport and is considered to be a gatekeeper for active Ca2+ absorption
  • potentially involved in male fertility depending on Ca2+ absorption by TRPV6 in epididymal epithelia
  • function as epithelial Ca(2+) entry pathways in the epididymis, prostate, and placenta
  • 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
  • is a novel cell adhesion molecule (CAM) that directly regulates endothelial integrity and mediates the protective actions of L-Arg to endothelium via a NO-independent mechanism
  • TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues
  • play a critical role in calcium uptake in epithelial tissues
  • TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside
    text transcellular calcium transport
    a component
    small molecule metal binding, nucleotide,
  • Mg2+
  • ATP
  • protein
  • colocalizing with calbindin
  • interacting with PDZK2
  • interacts with the N-terminal domain of RGS2 in a Ca(2+)-independent fashion and overexpression of RGS2 reduces the Na(+) and Ca(2+) current of TRPV6
  • interacting with WNK4 and TRPV5
  • interacting with PPIB (Stumpf 2008)
  • interaction between TRPV6 and NEDD4L WW1 and WW2 domains plays a critical role in controlling the degradation of TRPV6
  • functional interaction of TRPC1 with TRPV6 that negatively regulates Ca2+ influx (
  • NUMB interacts with TRPV6 through charged residues and inhibits its activity via the regulation of protein expression
  • ZFHX3 plays likely an important role in intracellular calcium homeostasis in mammary epithelial cells, at least in part, by regulating TRPV6
  • cell & other
    induced by by estrogens and the reproductive cycle at transcriptional levels
    repressed by TRPC1 (down-regulation of TRPV6 currents by TRPC1 may increase the cellular diversity to fine-tune Ca2+ homeostasis)
    Other modulated by Mg2+
    positively regulated by 1,25(OH)(2)D(3)
    regulated by the serine/threonine protein kinase isoforms SGK and SGK3, independently of the presence of the scaffold proteins NHERF1 and NHERF2
    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)
    highly regulated by 1,25(OH)2-vitamin D3 at the transcriptional level
    corresponding disease(s) TNHP1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate carcinoma advanced with metastatic lesions
    constitutional       gain of function
    plays a role in calcium stone formation in certain forms of absorptive hypercalciuria
    tumoral     --low  
    in esophageal squamous cell carcinoma (ESCC) tissues and cell lines
    Variant & Polymorphism
    Candidate gene molecular candidate for apical Ca2+ entry route in renal and intestinal epithelial cells
  • as a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients
  • Therapy target