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FLASH GENE

Symbol

TRPV5

contributors: mct/pgu - updated : 24-06-2015

HGNC name	transient receptor potential cation channel, subfamily V, member 5
HGNC id	3145

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

DNA

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_019841 15 - 2486 NP_062815 - 729 - 2009 19157541

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland         Hearing/Equilibrium ear inner       Homo sapiens Lymphoid/Immune lymph node         Urinary kidney tubule collecting duct   highly Homo sapiens   kidney tubule convoluted tubule distal tubule highly Homo sapiens Visual eye         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining retinal pigment epithelium (RPE)     Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	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)

HOMOLOGY

interspecies

homolog to rabbit Ecac

intraspecies

homolog to TRPV6

Homologene

FAMILY	transient receptor family
	mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels

CATEGORY

receptor , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
text	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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

active transport

text	transcellular calcium transport

PATHWAY

metabolism

signaling

a component	homotetramer and probably heterotetramer with TRPV6
	MCOLN3 and TRPV5 associate to form a novel heteromeric ion channel

INTERACTION

DNA

RNA

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

REGULATION

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)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   leading to baseline infammation in the lung

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous urinary   TRPV5 represents a potential therapeutic target for disorders with altered Ca(2+) homeostasis

ANIMAL & CELL MODELS