TPCN1 explained

Two pore segment channel 1 (TPC1) is a human protein encoded by the TPCN1 gene.^[1] The protein encoded by this gene is an ion channel. In contrast to other calcium and sodium channels which have four homologous domains, each containing six transmembrane segments (S1 to S6), TPCN1 only contains two domains (each containing segments S1 to S6).^{[2] [3] [4]}

Structure

The structure of a TPC1 ortholog from Arabidopsis thaliana has been solved by two laboratories.^{[5] [6]} The structures were solved using X-ray crystallography and contained the fold of a voltage-gated ion channel and EF hands. Only a single voltage sensor domain appears to responsible for voltage sensing.

Filoviral infections

Genetic knockout and pharmacological inhibition experiments demonstrate that the two-pore channels, TPC1 and TPC2, are required for infection by Filoviruses Ebola and Marburg in mice.^[7]

See also

• Two-pore channel

Further reading

• Ishibashi K, Suzuki M, Imai M . Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels . Biochemical and Biophysical Research Communications . 270 . 2 . 370–6 . April 2000 . 10753632 . 10.1006/bbrc.2000.2435 .
• Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O . Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain . DNA Research . 6 . 5 . 329–36 . October 1999 . 10574461 . 10.1093/dnares/6.5.329 . free .
• Clapham DE, Garbers DL . International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels . Pharmacological Reviews . 57 . 4 . 451–4 . December 2005 . 16382101 . 10.1124/pr.57.4.7 . 35096827 .
• Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT, Lin P, Xiao R, Wang C, Zhu Y, Lin Y, Wyatt CN, Parrington J, Ma J, Evans AM, Galione A, Zhu MX . NAADP mobilizes calcium from acidic organelles through two-pore channels . Nature . 459 . 7246 . 596–600 . May 2009 . 19387438 . 2761823 . 10.1038/nature08030 . 2009Natur.459..596C .
• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Research . 9 . 3 . 99–106 . June 2002 . 12168954 . 10.1093/dnares/9.3.99 . 10.1.1.500.923 .

Notes and References

1. Web site: Entrez Gene: two pore segment channel 1.
2. Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O . Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain . DNA Research . 6 . 5 . 329–36 . October 1999 . 10574461 . 10.1093/dnares/6.5.329 . free .
3. Ishibashi K, Suzuki M, Imai M . Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels . Biochemical and Biophysical Research Communications . 270 . 2 . 370–6 . April 2000 . 10753632 . 10.1006/bbrc.2000.2435 .
4. Clapham DE, Garbers DL . International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels . Pharmacological Reviews . 57 . 4 . 451–4 . December 2005 . 16382101 . 10.1124/pr.57.4.7 . 35096827 .
5. Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y, Cang C, Ren D, Jiang Y . Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana . Nature . 531 . 7593 . 196–201 . March 2016 . 26689363 . 10.1038/nature16446 . 4841471. 2016Natur.531..196G .
6. Kintzer AF, Stroud RM . Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana . Nature . 531 . 7593 . 258–62 . March 2016 . 26961658 . 10.1038/nature17194 . 4863712. 2016Natur.531..258K .
7. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA . Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment . Science . 347 . 6225 . 995–8 . February 2015 . 25722412 . 10.1126/science.1258758 . 4550587.