Nomenclature: TRPP2

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 805 10q24.31 PKD2L1 polycystic kidney disease 2-like 1 2,7-8
Mouse 6 1 760 19 C3 Pkd2l1 polycystic kidney disease 2-like 1 6-7
Rat 6 1 676 1q56 Pkd2l1 polycystic kidney disease 2-like 1
Previous and Unofficial Names
PCL (polycystin-like)
PKDL
PKD2L
PKD2L1
PKDL2
polycystic kidney disease 2-like 1 protein
PCL
TRPP3
transient receptor potential cation channel, subfamily P, member 3
Pkd2l1_predicted
LOC293937
polycystic kidney disease 2-like 1
polycystic kidney disease 2-like 1 (predicted)
polycystin-L
BC046386
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
PKD1L3 4
Other Associated Proteins
Name References
Not determined
Functional Characteristics
γ = 105–137 pS (outward conductance) 184–399 pS (inward conductance), conducts mono- and di-valent cations with a preference for divalents (PCa/PNa = 4.0–4.3); steady state currents rectify outwardly, whereas instantaneous currents show strong inward rectification; activated and subsequently inactivated by intracellular Ca2+ (human, but not mouse); inhibited by extracellular acidification and potentiated by extracellular alkalization
Ion Selectivity and Conductance
Species:  Human
Rank order:  Na+ [137.0 pS] > Ca2+ [120.0 - 135.0 pS] = Sr2+ = Ba2+
References:  1
Activators (Human)
Low constitutive activity, enhanced by membrane depolarization; changes in cell volume affect voltage-dependent gating (increased channel opening probability with cell swelling)
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Intracellular Ca2+ Hs Agonist - - 5x10-3 -150.0 – 100.0 1
Conc range: 5x10-3 M [1]
Holding voltage: -150.0 – 100.0 mV
Extracellular Ca2+ Hs Agonist - - 1x10-6 -60.0 – -50.0 1
Conc range: 1x10-6 M [1]
Holding voltage: -60.0 – -50.0 mV
HCl Hs Agonist 1.89 pEC50 1.1x10-2 - 1.5x10-2 Physiological 4
pEC50 1.89 Conc range: 1.1x10-2 - 1.5x10-2 M [4]
Holding voltage: Physiological
citric acid Hs Agonist 1.7 pEC50 1.5x10-2 - 3x10-2 Physiological 4
pEC50 1.7 Conc range: 1.5x10-2 - 3x10-2 M [4]
Holding voltage: Physiological
malic acid Hs Agonist - - - Physiological 4
[4]
Holding voltage: Physiological
Activator Comments
Chen et al [1] expressed human TRPP2 in Xenopus oocytes and proposed increased currents on increasing external or (inferred) internal Ca2+ levels and noted a decrease in channel activity on lowering external pH (7.5>6). TRPP2 and PKD1L3 are coexpressed in sour taste receptor cells of the tongue. Coexpression of the PDK1L3 and TRPP2 is necessary for functional cell surface expression, presumably as a heteromeric complex, where they are activated by acid pH [4].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
flufenamic acid Hs - - - 5x10-4 -50.0 1
Conc range: 5x10-4 M [1]
Holding voltage: -50.0 mV
Gd3+ Hs - - - 1x10-4 -50.0 1
Conc range: 1x10-4 M [1]
Holding voltage: -50.0 mV
La3+ Hs - - - 1x10-4 -50.0 1
Conc range: 1x10-4 M [1]
Holding voltage: -50.0 mV
phenamil Hs - 6.9 pIC50 - -
pIC50 6.9 (IC50 1.4x10-7 M)
benzamil Hs - 6.0 pIC50 - -
pIC50 6.0 (IC50 1.1x10-6 M)
EIPA Hs - 5.0 pIC50 - -
pIC50 5.0 (IC50 1.05x10-5 M)
amiloride Hs - 3.8 pIC50 - -
pIC50 3.8 (IC50 1.43x10-4 M)
flufenamate Hs - - - - -
Channel Blocker Comments
The block refers to the inhibition of the presumed current carried by human TRPP2 in Xenopus laevis oocytes.
Tissue Distribution
Adult: Heart, skeletal muscle, brain, spleen, testis, retina
Fetal: Widely expressed, higher expression than adult.
Species:  Human
Technique:  Northern Blot
References:  7-8
"Taste tissue", testis > wide expression at low levels.
Species:  Mouse
Technique:  RT-PCR
References:  4
Sour taste receptors of the tongue, circumvallate and foliate papilla, cells surrounding the central canal of the spinal cord.
Species:  Mouse
Technique:  Immunohistochemistry
References:  3-4
Circumvallate, foliate and fungiform papillae, palate, cells surrounding the central canal of the spinal cord, hypothalamus.
Species:  Mouse
Technique:  In situ hybridisation
References:  3-5
Functional Assays
Imaging of calcium influx into cells stimulated by citric acid or HCL.
Species:  Mouse
Tissue:  HEK 293 cells transiently expressing TRPP2 and PKD1L3
Response measured:  Intracellular Ca2+
References:  4
Patch-clamp recordings of the response of TRPP2-positive cells to changes in pH.
Species:  Mouse
Tissue:  Spinal cord slice preparation
Response measured:  Action potential frequency
References:  3
Patch clamp measurement of non-selective cation currents at rest and stimulated by Ca2+.
Species:  Human
Tissue:  expressed in Xenopus oocytes
Response measured:  Current
References:  1
Physiological Functions
Acid sensing in sour taste.
Species:  Mouse
Tissue:  Tongue, palate.
References:  3-4
Acid sensing in cerebrospinal fluid.
Species:  Mouse
Tissue:  Spinal cord cells adjacent to the central canal.
References:  3
Clinically-Relevant Mutations and Pathophysiology Comments
TRPP2 is deleted in the Krd mouse. This mouse has defects in structures of the kidney, retina and optic disc, however the Krd deletion is a 7cM transgene-induce deletion on chromosome 19 that includes the Pax2 locus [7].

REFERENCES

1. Chen XZ, Vassilev PM, Basora N, Peng JB, Nomura H, Segal Y, Brown EM, Reeders ST, Hediger MA, Zhou J. (1999) Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature401 (6751): 383-6. [PMID:10517637]

2. Guo L, Chen M, Basora N, Zhou J. (2000) The human polycystic kidney disease 2-like (PKDL) gene: exon/intron structure and evidence for a novel splicing mechanism. Mamm. Genome11 (1): 46-50. [PMID:10602992]

3. Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Tränkner D, Ryba NJ, Zuker CS. (2006) The cells and logic for mammalian sour taste detection. Nature442 (7105): 934-8. [PMID:16929298]

4. Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H. (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc. Natl. Acad. Sci. U.S.A.103 (33): 12569-74. [PMID:16891422]

5. LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL. (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J. Neurochem.98 (1): 68-77. [PMID:16805797]

6. Murakami M, Ohba T, Xu F, Shida S, Satoh E, Ono K, Miyoshi I, Watanabe H, Ito H, Iijima T. (2005) Genomic organization and functional analysis of murine PKD2L1. J. Biol. Chem.280 (7): 5626-35. [PMID:15548533]

7. Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T, Weremowicz S, Ji W, Morton CC, Meisler M, Reeders ST, Zhou J. (1998) Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J. Biol. Chem.273 (40): 25967-73. [PMID:9748274]

8. Wu G, Hayashi T, Park JH, Dixit M, Reynolds DM, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S. (1998) Identification of PKD2L, a human PKD2-related gene: tissue-specific expression and mapping to chromosome 10q25. Genomics54 (3): 564-8. [PMID:9878261]

To cite this database page, please use the following:

David E. Clapham, Bernd Nilius, Grzegorz Owsianik.
Transient Receptor Potential channels: TRPP2. Last modified on 30/01/2014. Accessed on 28/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=505.

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