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TRPP2

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Target not currently curated in GtoImmuPdb

Target id: 505

Nomenclature: TRPP2

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 805 10q24.31 PKD2L1 polycystin 2 like 1, transient receptor potential cation channel 4,9,11
Mouse 6 1 760 19 C3 Pkd2l1 polycystic kidney disease 2-like 1 8-9
Rat 6 1 676 1q56 Pkd2l1 polycystin 2 like 1, transient receptor potential cation channel
Previous and Unofficial Names Click here for help
PKD2L1 | PKDL | PKDL2 | TRPP3 | transient receptor potential cation channel, subfamily P, member 3 | polycystic kidney disease 2-like 1 | polycystin 2 like 1 | polycystin 2 like 1, transient receptor potential cation channel
Database Links Click here for help
Alphafold Q9P0L9 (Hs)
Ensembl Gene ENSG00000107593 (Hs), ENSMUSG00000037578 (Mm), ENSRNOG00000012591 (Rn)
Entrez Gene 9033 (Hs), 329064 (Mm), 293937 (Rn)
Human Protein Atlas ENSG00000107593 (Hs)
KEGG Gene hsa:9033 (Hs), mmu:329064 (Mm), rno:293937 (Rn)
OMIM 604532 (Hs)
Pharos Q9P0L9 (Hs)
RefSeq Nucleotide NM_016112 (Hs), NM_181422 (Mm), NM_001106352 (Rn)
RefSeq Protein NP_057196 (Hs), NP_852087 (Mm), NP_001099822 (Rn)
UniProtKB Q9P0L9 (Hs)
Wikipedia PKD2L1 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
PKD1L3 6
Other Associated Proteins
Name References
Not determined
Functional Characteristics Click here for help
TRPP2 is a nonselective cation channel functionally expressed on primary cilia and/or the plasma membrane depending on cell type. It can form a functional channel with PC1-L1 on primary cilia of retinal pigmented epithelial cells. TRPP2 (PKD2L1) displays calcium dependent activation. Calcium accumulation due to prolonged channel activity may lead to outward-moving Ca2+ ions within the pore to close the channel [2]. TRPP2 permeates K+, Na+ and Ca2+ with the single-channel conductance of 189 pS for K+, 156 for Na+, and 53 pS for Ca2+, respectively [3]. PKD2L1 forms a heteromeric channel with PC-1L3 (PKD1L3) that may be activated by intracellular Ca2+ [10].
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Na+ [137.0 pS] > Ca2+ [120.0 - 135.0 pS] = Sr2+ = Ba2+
References:  1
Activators (Human)
Calmidazolium (in primary cilia): 10 µM

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Intracellular Ca2+ Click here for species-specific activity table Hs Agonist - - 5x10-3 -150.0 – 100.0 1
⤷ Conc range: 5x10-3 M [1]
Holding voltage: -150.0 – 100.0 mV
Extracellular Ca2+ Click here for species-specific activity table 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 1.9 pEC50 1.1x10-2 - 1.5x10-2 Physiological 6
⤷ pEC50 1.9 Conc range: 1.1x10-2 - 1.5x10-2 M [6]
Holding voltage: Physiological
citric acid Small molecule or natural product Ligand has a PDB structure Hs Agonist 1.7 pEC50 1.5x10-2 - 3x10-2 Physiological 6
⤷ pEC50 1.7 Conc range: 1.5x10-2 - 3x10-2 M [6]
Holding voltage: Physiological
malic acid Small molecule or natural product Hs Agonist - - - Physiological 6
⤷ [6]
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 [6].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
flufenamic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - - - 5x10-4 -50.0 1
⤷ Conc range: 5x10-4 M [1]
Holding voltage: -50.0 mV
Gd3+ Click here for species-specific activity table Hs - - - 1x10-4 -50.0 1
⤷ Conc range: 1x10-4 M [1]
Holding voltage: -50.0 mV
La3+ Click here for species-specific activity table Hs - - - 1x10-4 -50.0 1
⤷ Conc range: 1x10-4 M [1]
Holding voltage: -50.0 mV
phenamil Small molecule or natural product Hs - 6.9 pIC50 - -
⤷ pIC50 6.9 (IC50 1.4x10-7 M)
benzamil Small molecule or natural product Click here for species-specific activity table Hs - 6.0 pIC50 - -
⤷ pIC50 6.0 (IC50 1.1x10-6 M)
ethylisopropylamiloride Small molecule or natural product Click here for species-specific activity table Hs - 5.0 pIC50 - -
⤷ pIC50 5.0 (IC50 1.05x10-5 M)
amiloride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - 3.8 pIC50 - -
⤷ pIC50 3.8 (IC50 1.43x10-4 M)
flufenamate Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
Channel Blocker Comments
The block refers to the inhibition of the presumed current carried by human TRPP2 in Xenopus laevis oocytes.
Tissue Distribution Click here for help
Adult: Heart, skeletal muscle, brain, spleen, testis, retina
Fetal: Widely expressed, higher expression than adult.
Species:  Human
Technique:  Northern Blot
References:  9,11
"Taste tissue", testis > wide expression at low levels.
Species:  Mouse
Technique:  RT-PCR
References:  6
Sour taste receptors of the tongue, circumvallate and foliate papilla, cells surrounding the central canal of the spinal cord.
Species:  Mouse
Technique:  Immunohistochemistry
References:  5-6
Circumvallate, foliate and fungiform papillae, palate, cells surrounding the central canal of the spinal cord, hypothalamus.
Species:  Mouse
Technique:  In situ hybridisation
References:  5-7
Functional Assays Click here for help
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:  6
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:  5
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 Click here for help
Acid sensing in sour taste.
Species:  Mouse
Tissue:  Tongue, palate.
References:  5-6
Acid sensing in cerebrospinal fluid.
Species:  Mouse
Tissue:  Spinal cord cells adjacent to the central canal.
References:  5
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 [9].

References

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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. Nature, 401 (6751): 383-6. [PMID:10517637]

2. DeCaen PG, Liu X, Abiria S, Clapham DE. (2016) Atypical calcium regulation of the PKD2-L1 polycystin ion channel. Elife, 5. [PMID:27348301]

3. Esarte Palomero O, Larmore M, DeCaen PG. (2023) Polycystin Channel Complexes. Annu Rev Physiol, 85: 425-448. [PMID:36763973]

4. 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 Genome, 11 (1): 46-50. [PMID:10602992]

5. 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. Nature, 442 (7105): 934-8. [PMID:16929298]

6. 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 USA, 103 (33): 12569-74. [PMID:16891422]

7. 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]

8. 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]

9. Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T, Weremowicz S, Ji W, Morton CC, Meisler M, Reeders ST et al.. (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]

10. Su Q, Chen M, Wang Y, Li B, Jing D, Zhan X, Yu Y, Shi Y. (2021) Structural basis for Ca2+ activation of the heteromeric PKD1L3/PKD2L1 channel. Nat Commun, 12 (1): 4871. [PMID:34381056]

11. 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. Genomics, 54 (3): 564-8. [PMID:9878261]

Contributors

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