TPCN2 explained

Two pore segment channel 2 (TPC2) is a protein which in humans is encoded by the TPCN2 gene.^[1] TPC2 is an ion channel, however, in contrast to other calcium and sodium channels which have four homologous domains, each containing 6 transmembrane segments (S1 to S6), TPCN1 only contains two domain (each containing segments S1 to S6).^[2]

Structure

TPC2 is homologous to TPC1, the best characterized member of the TPC family. The structure of a TPC1 ortholog from Arabidopsis thaliana has been solved by two laboratories.^{[3] [4]} The structures were solved using X-ray crystallography and contained the fold of a voltage-gated ion channel and EF hands.

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.^[5]

See also

• Two-pore channel

Further reading

• Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Jakobsdottir M, Steinberg S, Gudjonsson SA, Palsson A, Thorleifsson G, Pálsson S, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Vermeulen SH, Goldstein AM, Tucker MA, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K . Two newly identified genetic determinants of pigmentation in Europeans . Nature Genetics . 40 . 7 . 835–7 . July 2008 . 18488028 . 10.1038/ng.160 . 13411482 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• 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 .
• Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y . Human chromosome 11 DNA sequence and analysis including novel gene identification . Nature . 440 . 7083 . 497–500 . March 2006 . 16554811 . 10.1038/nature04632 . 2006Natur.440..497T . free .
• Fu GK, Wang JT, Yang J, Au-Young J, Stuve LL . Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes . Genomics . 84 . 1 . 205–10 . July 2004 . 15203218 . 10.1016/j.ygeno.2004.01.011 .

Notes and References

1. Web site: Entrez Gene: two pore segment channel 2.
2. 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 .
3. 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 .
4. 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 .
5. 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.