TPCN1

Two pore segment channel 1 (TPC1) is a human protein encoded by the TPCN1 gene.[5] 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 6 transmembrane segments (S1 to S6), TPCN1 only contains two domains (each containing segments S1 to S6).[6][7][8]

TPCN1
Identifiers
Aliases	TPCN1, TPC1, two pore segment channel 1
External IDs	OMIM: 609666 MGI: 2182472 HomoloGene: 9905 GeneCards: TPCN1
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.13 Start 113,221,050 bp[1] End 113,298,585 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 120,534,153 bp[2] End 120,588,673 bp[2]
Gene ontology Molecular function • calcium channel activity • voltage-gated ion channel activity • ion channel activity • GO:0001948 protein binding • identical protein binding • NAADP-sensitive calcium-release channel activity • voltage-gated calcium channel activity • calcium activated cation channel activity Cellular component • integral component of membrane • endosome • membrane • cell membrane • lysosomal membrane • lysosome • endosome membrane • CatSper complex Biological process • membrane depolarization during action potential • positive regulation of autophagy • regulation of ion transmembrane transport • ion transport • ion transmembrane transport • calcium ion transmembrane transport • calcium ion transport • transmembrane transport • release of sequestered calcium ion into cytosol • flagellated sperm motility Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	53373	252972
Ensembl	ENSG00000186815	ENSMUSG00000032741
UniProt	Q9ULQ1	Q9EQJ0
RefSeq (mRNA)	NM_001143819 NM_001301214 NM_017901 NM_001351346 NM_001351347	NM_145853
RefSeq (protein)	NP_001137291 NP_001288143 NP_060371 NP_001338275 NP_001338276	NP_665852
Location (UCSC)	Chr 12: 113.22 – 113.3 Mb	Chr 5: 120.53 – 120.59 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

The structure of a TPC1 ortholog from Arabidopsis thaliana has been solved by two laboratories.[9][10] 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 Two-pore Channels, TPC1 and TPC2, are required for infection by Filoviruses Ebola and Marburg in mice.[11]

See also

• Two-pore channel

References

1. GRCh38: Ensembl release 89: ENSG00000186815 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032741 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: two pore segment channel 1".
6. Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (October 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
7. Ishibashi K, Suzuki M, Imai M (April 2000). "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. doi:10.1006/bbrc.2000.2435. PMID 10753632.
8. Clapham DE, Garbers DL (December 2005). "International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels". Pharmacological Reviews. 57 (4): 451–4. doi:10.1124/pr.57.4.7. PMID 16382101.
9. Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y, Cang C, Ren D, Jiang Y (March 2016). "Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana". Nature. 531 (7593): 196–201. doi:10.1038/nature16446. PMC 4841471. PMID 26689363.
10. Kintzer AF, Stroud RM (March 2016). "Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana". Nature. 531 (7593): 258–62. doi:10.1038/nature17194. PMC 4863712. PMID 26961658.
11. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA (February 2015). "Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment". Science. 347 (6225): 995–8. doi:10.1126/science.1258758. PMC 4550587. PMID 25722412.

Further reading

• Ishibashi K, Suzuki M, Imai M (April 2000). "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. doi:10.1006/bbrc.2000.2435. PMID 10753632.
• Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (October 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
• Clapham DE, Garbers DL (December 2005). "International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels". Pharmacological Reviews. 57 (4): 451–4. doi:10.1124/pr.57.4.7. PMID 16382101.
• 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 (May 2009). "NAADP mobilizes calcium from acidic organelles through two-pore channels". Nature. 459 (7246): 596–600. doi:10.1038/nature08030. PMC 2761823. PMID 19387438.
• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. CiteSeerX 10.1.1.500.923. doi:10.1093/dnares/9.3.99. PMID 12168954.

External links

• TPCN1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)