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HVCN1

{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{Infobox_gene}}

Voltage-gated hydrogen channel 1 is a protein that in humans is encoded by the HVCN1 gene.

Voltage-gated hydrogen channel 1 is a voltage-gated proton channel that has been shown to allow proton transport into phagosomes{{cite journal | vauthors = Murphy R, DeCoursey TE | title = Charge compensation during the phagocyte respiratory burst | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1757 | issue = 8 | pages = 996–1011 | date = August 2006 | pmid = 16483534 | doi = 10.1016/j.bbabio.2006.01.005 }}{{cite journal | vauthors = Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K, Dinsdale D, Pulford K, Khan M, Musset B, Cherny VV, Morgan D, Gascoyne RD, Vigorito E, DeCoursey TE, MacLennan IC, Dyer MJ | title = HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species | journal = Nature Immunology | volume = 11 | issue = 3 | pages = 265–272 | date = March 2010 | pmid = 20139987 | pmc = 3030552 | doi = 10.1038/ni.1843 }} and out of many types of cells including spermatozoa, electrically excitable cells and respiratory epithelial cells.{{cite journal | vauthors = Capasso M, DeCoursey TE, Dyer MJ | title = pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1 | journal = Trends in Cell Biology | volume = 21 | issue = 1 | pages = 20–28 | date = January 2011 | pmid = 20961760 | pmc = 3014425 | doi = 10.1016/j.tcb.2010.09.006 }} The proton-conducting HVCN1 channel has only transmembrane domains corresponding to the S1-S4 voltage sensing domains (VSD) of voltage-gated potassium channels and voltage-gated sodium channels.{{cite journal | vauthors = Lee SY, Letts JA, MacKinnon R | title = Functional reconstitution of purified human Hv1 H+ channels | journal = Journal of Molecular Biology | volume = 387 | issue = 5 | pages = 1055–1060 | date = April 2009 | pmid = 19233200 | pmc = 2778278 | doi = 10.1016/j.jmb.2009.02.034 }} Molecular simulation is consistent with a water-filled pore that can function as a "water wire" for allowing hydrogen bonded H+ to cross the membrane.{{cite journal | vauthors = Wood ML, Schow EV, Freites JA, White SH, Tombola F, Tobias DJ | title = Water wires in atomistic models of the Hv1 proton channel | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1818 | issue = 2 | pages = 286–293 | date = February 2012 | pmid = 21843503 | pmc = 3245885 | doi = 10.1016/j.bbamem.2011.07.045 }}{{cite journal | vauthors = Ramsey IS, Mokrab Y, Carvacho I, Sands ZA, Sansom MS, Clapham DE | title = An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1 | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 7 | pages = 869–875 | date = July 2010 | pmid = 20543828 | pmc = 4035905 | doi = 10.1038/nsmb.1826 }} However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity.{{cite journal | vauthors = Musset B, Smith SM, Rajan S, Morgan D, Cherny VV, Decoursey TE | title = Aspartate 112 is the selectivity filter of the human voltage-gated proton channel. | journal = Nature | volume = 480 | issue = 7376 | pages = 273–277 | date = 23 October 2011 | pmid = 22020278 | pmc = 3237871 | doi = 10.1038/nature10557 | bibcode = 2011Natur.480..273M }} Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation.{{cite journal | vauthors = Dudev T, Musset B, Morgan D, Cherny VV, Smith SM, Mazmanian K, DeCoursey TE, Lim C | title = Selectivity Mechanism of the Voltage-gated Proton Channel, HV1. | journal = Scientific Reports | volume = 5 | pages = 10320 | date = 8 May 2015 | pmid = 25955978 | pmc = 4429351 | doi = 10.1038/srep10320 | bibcode = 2015NatSR...510320D }} The HVCN1 protein has been shown to exist as a dimer with two functioning pores.{{cite journal | vauthors = Gonzalez C, Koch HP, Drum BM, Larsson HP | title = Strong cooperativity between subunits in voltage-gated proton channels | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 1 | pages = 51–56 | date = January 2010 | pmid = 20023639 | pmc = 2935852 | doi = 10.1038/nsmb.1739 }}{{cite journal | vauthors = Tombola F, Ulbrich MH, Kohout SC, Isacoff EY | title = The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 1 | pages = 44–50 | date = January 2010 | pmid = 20023640 | pmc = 2925041 | doi = 10.1038/nsmb.1738 }} Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.{{cite journal | vauthors = DeCoursey TE | title = Voltage-gated proton channels: what's next? | journal = The Journal of Physiology | volume = 586 | issue = 22 | pages = 5305–5324 | date = November 2008 | pmid = 18801839 | pmc = 2655391 | doi = 10.1113/jphysiol.2008.161703 }}

As a drug target

Small molecule inhibitors of the HVCN1 channel are being developed as chemotherapeutics and anti-inflammatory agents.{{cite journal | vauthors = Hong L, Pathak MM, Kim IH, Ta D, Tombola F | title = Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains | journal = Neuron | volume = 77 | issue = 2 | pages = 274–287 | date = January 2013 | pmid = 23352164 | pmc = 3559007 | doi = 10.1016/j.neuron.2012.11.013 }}

References

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Further reading

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  • {{cite journal | vauthors = Li SJ, Zhao Q, Zhou Q, Unno H, Zhai Y, Sun F | title = The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1. | journal = Journal of Biological Chemistry | volume = 285 | issue = 16 | pages = 12047–12054 | date = Apr 2010 | pmid = 20147290 | pmc = 2852942 | doi = 10.1074/jbc.M109.040360 | doi-access = free }}
  • {{cite journal | vauthors = Musset B, Smith SM, Rajan S, Cherny VV, Morgan D, DeCoursey TE | title = Oligomerization of the voltage-gated proton channel. | journal = Channels | location = Austin, Tex. | volume = 4 | issue = 4 | pages = 260–265 | year = 2010 | pmid = 20676047 | pmc = 3025757 | doi = 10.4161/chan.4.4.12789 }}
  • {{cite journal | vauthors = Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y | title = Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel. | journal = Cell | volume = 140 | issue = 3 | pages = 327–337 | date = Feb 2010 | pmid = 20144758 | doi = 10.1016/j.cell.2009.12.053 | s2cid = 7952753 | doi-access = free }}
  • {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
  • {{cite journal | vauthors = Musset B, Capasso M, Cherny VV, Morgan D, Bhamrah M, Dyer MJ, DeCoursey TE | title = Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes. | journal = Journal of Biological Chemistry | volume = 285 | issue = 8 | pages = 5117–5121 | date = Feb 2010 | pmid = 20037153 | pmc = 2820736 | doi = 10.1074/jbc.C109.082727 | doi-access = free }}
  • {{cite journal | vauthors = Petheo GL, Orient A, Barath M, Kovacs I, Rethi B, Lanyi A, Rajki A, Rajnavolgyi E, Geiszt M | title = Molecular and functional characterization of Hv1 proton channel in human granulocytes. | journal = PLOS ONE | volume = 5 | issue = 11 | pages = e14081 | date = Nov 2010 | pmid = 21124855 | pmc = 2990768 | doi = 10.1371/journal.pone.0014081 | bibcode = 2010PLoSO...514081P | doi-access = free }}
  • {{cite journal | vauthors = Sasaki M, Takagi M, Okamura Y | title = A voltage sensor-domain protein is a voltage-gated proton channel. | journal = Science | location = New York, N.Y. | volume = 312 | issue = 5773 | pages = 589–592 | date = Apr 2006 | pmid = 16556803 | doi = 10.1126/science.1122352 | bibcode = 2006Sci...312..589S | s2cid = 10259815 | doi-access = free }}
  • {{cite journal | vauthors = Lee SY, Letts JA, Mackinnon R | title = Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 22 | pages = 7692–7695 | date = Jun 2008 | pmid = 18509058 | pmc = 2409406 | doi = 10.1073/pnas.0803277105 | bibcode = 2008PNAS..105.7692L | doi-access = free }}
  • {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. | journal = Genome Research | volume = 14 | issue = 9 | pages = 1711–1718 | date = Sep 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }}
  • {{cite journal | vauthors = Li SJ, Zhao Q, Zhou Q, Zhai Y | title = Expression, purification, crystallization and preliminary crystallographic study of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1. | journal = Acta Crystallographica. Section F, Structural Biology and Crystallization Communications | volume = 65 | issue = Pt 3 | pages = 279–281 | date = Mar 2009 | pmid = 19255483 | pmc = 2650464 | doi = 10.1107/S1744309109003777 }}
  • {{cite journal | vauthors = Suenaga T, Arase H, Yamasaki S, Kohno M, Yokosuka T, Takeuchi A, Hattori T, Saito T | title = Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function. | journal = European Journal of Immunology | volume = 37 | issue = 11 | pages = 3197–3207 | date = Nov 2007 | pmid = 17948262 | doi = 10.1002/eji.200737052 | s2cid = 25376411 | doi-access = free }}
  • {{cite journal | vauthors = Iovannisci D, Illek B, Fischer H | title = Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T. | journal = The Journal of General Physiology | volume = 136 | issue = 1 | pages = 35–46 | date = Jul 2010 | pmid = 20548053 | pmc = 2894549 | doi = 10.1085/jgp.200910379 }}
  • {{cite journal | vauthors = Musset B, Cherny VV, Morgan D, Okamura Y, Ramsey IS, Clapham DE, DeCoursey TE | title = Detailed comparison of expressed and native voltage-gated proton channel currents. | journal = The Journal of Physiology | volume = 586 | issue = 10 | pages = 2477–2486 | date = May 2008 | pmid = 18356202 | pmc = 2464343 | doi = 10.1113/jphysiol.2007.149427 }}
  • {{cite journal | vauthors = Ramsey IS, Moran MM, Chong JA, Clapham DE | title = A voltage-gated proton-selective channel lacking the pore domain. | journal = Nature | volume = 440 | issue = 7088 | pages = 1213–1216 | date = Apr 2006 | pmid = 16554753 | pmc = 4084761 | doi = 10.1038/nature04700 | bibcode = 2006Natur.440.1213R }}
  • {{cite journal | vauthors = Sakata S, Kurokawa T, Norholm MH, Takagi M, Okochi Y, Heijne G, Okamura Y | title = Functionality of the voltage-gated proton channel truncated in S4. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 5 | pages = 2313–2318 | date = Feb 2010 | pmid = 20018719 | pmc = 2836681 | doi = 10.1073/pnas.0911868107 | bibcode = 2010PNAS..107.2313S | doi-access = free }}

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{{Ion channels|g4}}

Category:Ion channels