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Protein-coding gene in the species Homo sapiens
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 [ 5] [ 6] and out of many types of cells including spermatozoa , electrically excitable cells and respiratory epithelial cells.[ 7] 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 .[ 8] 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.[ 9] [ 10] However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity.[ 11] Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation.[ 12] The HVCN1 protein has been shown to exist as a dimer with two functioning pores.[ 13] [ 14] Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.[ 15]
Small molecule inhibitors of the HVCN1 channel are being developed as chemotherapeutics and anti-inflammatory agents.[ 16]
^ a b c GRCh38: Ensembl release 89: ENSG00000122986 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064267 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Murphy R, DeCoursey TE (August 2006). "Charge compensation during the phagocyte respiratory burst". Biochimica et Biophysica Acta (BBA) - Bioenergetics . 1757 (8): 996– 1011. doi :10.1016/j.bbabio.2006.01.005 . PMID 16483534 .
^ Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K, et al. (March 2010). "HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species" . Nature Immunology . 11 (3): 265– 272. doi :10.1038/ni.1843 . PMC 3030552 . PMID 20139987 .
^ Capasso M, DeCoursey TE, Dyer MJ (January 2011). "pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1" . Trends in Cell Biology . 21 (1): 20– 28. doi :10.1016/j.tcb.2010.09.006 . PMC 3014425 . PMID 20961760 .
^ Lee SY, Letts JA, MacKinnon R (April 2009). "Functional reconstitution of purified human Hv1 H+ channels" . Journal of Molecular Biology . 387 (5): 1055– 1060. doi :10.1016/j.jmb.2009.02.034 . PMC 2778278 . PMID 19233200 .
^ Wood ML, Schow EV, Freites JA, White SH, Tombola F, Tobias DJ (February 2012). "Water wires in atomistic models of the Hv1 proton channel" . Biochimica et Biophysica Acta (BBA) - Biomembranes . 1818 (2): 286– 293. doi :10.1016/j.bbamem.2011.07.045 . PMC 3245885 . PMID 21843503 .
^ Ramsey IS, Mokrab Y, Carvacho I, Sands ZA, Sansom MS, Clapham DE (July 2010). "An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1" . Nature Structural & Molecular Biology . 17 (7): 869– 875. doi :10.1038/nsmb.1826 . PMC 4035905 . PMID 20543828 .
^ Musset B, Smith SM, Rajan S, Morgan D, Cherny VV, Decoursey TE (23 October 2011). "Aspartate 112 is the selectivity filter of the human voltage-gated proton channel" . Nature . 480 (7376): 273– 277. Bibcode :2011Natur.480..273M . doi :10.1038/nature10557 . PMC 3237871 . PMID 22020278 .
^ Dudev T, Musset B, Morgan D, Cherny VV, Smith SM, Mazmanian K, et al. (8 May 2015). "Selectivity Mechanism of the Voltage-gated Proton Channel, HV1" . Scientific Reports . 5 : 10320. Bibcode :2015NatSR...510320D . doi :10.1038/srep10320 . PMC 4429351 . PMID 25955978 .
^
^ Tombola F, Ulbrich MH, Kohout SC, Isacoff EY (January 2010). "The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity" . Nature Structural & Molecular Biology . 17 (1): 44– 50. doi :10.1038/nsmb.1738 . PMC 2925041 . PMID 20023640 .
^ DeCoursey TE (November 2008). "Voltage-gated proton channels: what's next?" . The Journal of Physiology . 586 (22): 5305– 5324. doi :10.1113/jphysiol.2008.161703 . PMC 2655391 . PMID 18801839 .
^ Hong L, Pathak MM, Kim IH, Ta D, Tombola F (January 2013). "Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains" . Neuron . 77 (2): 274– 287. doi :10.1016/j.neuron.2012.11.013 . PMC 3559007 . PMID 23352164 .
Li SJ, Zhao Q, Zhou Q, Unno H, Zhai Y, Sun F (Apr 2010). "The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1" . Journal of Biological Chemistry . 285 (16): 12047– 12054. doi :10.1074/jbc.M109.040360 . PMC 2852942 . PMID 20147290 .
Musset B, Smith SM, Rajan S, Cherny VV, Morgan D, DeCoursey TE (2010). "Oligomerization of the voltage-gated proton channel" . Channels . 4 (4). Austin, Tex.: 260– 265. doi :10.4161/chan.4.4.12789 . PMC 3025757 . PMID 20676047 .
Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y (Feb 2010). "Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel" . Cell . 140 (3): 327– 337. doi :10.1016/j.cell.2009.12.053 . PMID 20144758 . S2CID 7952753 .
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Research . 16 (1): 55– 65. doi :10.1101/gr.4039406 . PMC 1356129 . PMID 16344560 .
Musset B, Capasso M, Cherny VV, Morgan D, Bhamrah M, Dyer MJ, et al. (Feb 2010). "Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes" . Journal of Biological Chemistry . 285 (8): 5117– 5121. doi :10.1074/jbc.C109.082727 . PMC 2820736 . PMID 20037153 .
Petheo GL, Orient A, Barath M, Kovacs I, Rethi B, Lanyi A, et al. (Nov 2010). "Molecular and functional characterization of Hv1 proton channel in human granulocytes" . PLOS ONE . 5 (11): e14081. Bibcode :2010PLoSO...514081P . doi :10.1371/journal.pone.0014081 . PMC 2990768 . PMID 21124855 .
Sasaki M, Takagi M, Okamura Y (Apr 2006). "A voltage sensor-domain protein is a voltage-gated proton channel" . Science . 312 (5773). New York, N.Y.: 589– 592. Bibcode :2006Sci...312..589S . doi :10.1126/science.1122352 . PMID 16556803 . S2CID 10259815 .
Lee SY, Letts JA, Mackinnon R (Jun 2008). "Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1" . Proceedings of the National Academy of Sciences of the United States of America . 105 (22): 7692– 7695. Bibcode :2008PNAS..105.7692L . doi :10.1073/pnas.0803277105 . PMC 2409406 . PMID 18509058 .
Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (Sep 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions" . Genome Research . 14 (9): 1711– 1718. doi :10.1101/gr.2435604 . PMC 515316 . PMID 15342556 .
Li SJ, Zhao Q, Zhou Q, Zhai Y (Mar 2009). "Expression, purification, crystallization and preliminary crystallographic study of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1" . Acta Crystallographica. Section F, Structural Biology and Crystallization Communications . 65 (Pt 3): 279– 281. doi :10.1107/S1744309109003777 . PMC 2650464 . PMID 19255483 .
Suenaga T, Arase H, Yamasaki S, Kohno M, Yokosuka T, Takeuchi A, et al. (Nov 2007). "Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function" . European Journal of Immunology . 37 (11): 3197– 3207. doi :10.1002/eji.200737052 . PMID 17948262 . S2CID 25376411 .
Iovannisci D, Illek B, Fischer H (Jul 2010). "Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T" . The Journal of General Physiology . 136 (1): 35– 46. doi :10.1085/jgp.200910379 . PMC 2894549 . PMID 20548053 .
Musset B, Cherny VV, Morgan D, Okamura Y, Ramsey IS, Clapham DE, et al. (May 2008). "Detailed comparison of expressed and native voltage-gated proton channel currents" . The Journal of Physiology . 586 (10): 2477– 2486. doi :10.1113/jphysiol.2007.149427 . PMC 2464343 . PMID 18356202 .
Ramsey IS, Moran MM, Chong JA, Clapham DE (Apr 2006). "A voltage-gated proton-selective channel lacking the pore domain" . Nature . 440 (7088): 1213– 1216. Bibcode :2006Natur.440.1213R . doi :10.1038/nature04700 . PMC 4084761 . PMID 16554753 .
Sakata S, Kurokawa T, Norholm MH, Takagi M, Okochi Y, Heijne G, et al. (Feb 2010). "Functionality of the voltage-gated proton channel truncated in S4" . Proceedings of the National Academy of Sciences of the United States of America . 107 (5): 2313– 2318. Bibcode :2010PNAS..107.2313S . doi :10.1073/pnas.0911868107 . PMC 2836681 . PMID 20018719 .