From Wikipedia, the free encyclopedia
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]
As a drug target
Small molecule inhibitors of the HVCN1 channel are being developed as
chemotherapeutics and
anti-inflammatory agents.
[16]
References
^
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". Biochim. Biophys. Acta . 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, Dinsdale D, Pulford K, Khan M, Musset B, Cherny VV, Morgan D, Gascoyne RD, Vigorito E, DeCoursey TE, MacLennan IC, Dyer MJ (March 2010).
"HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species" . Nat. Immunol . 11 (3): 265–72.
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 Cell Biol . 21 (1): 20–8.
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" . J. Mol. Biol . 387 (5): 1055–60.
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" . Biochim. Biophys. Acta . 1818 (2): 286–93.
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" . Nat. Struct. Mol. Biol . 17 (7): 869–75.
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): 273–7.
Bibcode :
2011Natur.480..273M .
doi :
10.1038/nature10557 .
PMC
3237871 .
PMID
22020278 .
^ Dudev, T; Musset, B; Morgan, D; Cherny, VV; Smith, SM; Mazmanian, K; DeCoursey, TE; Lim, C (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" . Nat. Struct. Mol. Biol . 17 (1): 44–50.
doi :
10.1038/nsmb.1738 .
PMC
2925041 .
PMID
20023640 .
^ DeCoursey TE (November 2008).
"Voltage-gated proton channels: what's next?" . J. Physiol . 586 (Pt 22): 5305–24.
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): 274–87.
doi :
10.1016/j.neuron.2012.11.013 .
PMC
3559007 .
PMID
23352164 .
Further reading
Li SJ, Zhao Q, Zhou Q, et al. (2010).
"The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1" . J. Biol. Chem . 285 (16): 12047–54.
doi :
10.1074/jbc.M109.040360 .
PMC
2852942 .
PMID
20147290 .
Musset B, Smith SM, Rajan S, et al. (2010).
"Oligomerization of the voltage-gated proton channel" . Channels (Austin) . 4 (4): 260–5.
doi :
10.4161/chan.4.4.12789 .
PMC
3025757 .
PMID
20676047 .
Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y (2010).
"Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel" . Cell . 140 (3): 327–37.
doi :
10.1016/j.cell.2009.12.053 .
PMID
20144758 .
S2CID
7952753 .
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006).
"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55–65.
doi :
10.1101/gr.4039406 .
PMC
1356129 .
PMID
16344560 .
Musset B, Capasso M, Cherny VV, et al. (2010).
"Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes" . J. Biol. Chem . 285 (8): 5117–21.
doi :
10.1074/jbc.C109.082727 .
PMC
2820736 .
PMID
20037153 .
Petheo GL, Orient A, Baráth M, et al. (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 (2006).
"A voltage sensor-domain protein is a voltage-gated proton channel" . Science . 312 (5773): 589–92.
Bibcode :
2006Sci...312..589S .
doi :
10.1126/science.1122352 .
PMID
16556803 .
S2CID
10259815 .
Lee SY, Letts JA, Mackinnon R (2008).
"Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1" . Proc. Natl. Acad. Sci. U.S.A . 105 (22): 7692–5.
Bibcode :
2008PNAS..105.7692L .
doi :
10.1073/pnas.0803277105 .
PMC
2409406 .
PMID
18509058 .
Suzuki Y, Yamashita R, Shirota M, et al. (2004).
"Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions" . Genome Res . 14 (9): 1711–8.
doi :
10.1101/gr.2435604 .
PMC
515316 .
PMID
15342556 .
Li SJ, Zhao Q, Zhou Q, Zhai Y (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 . 65 (Pt 3): 279–81.
doi :
10.1107/S1744309109003777 .
PMC
2650464 .
PMID
19255483 .
Suenaga T, Arase H, Yamasaki S, et al. (2007).
"Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function" . Eur. J. Immunol . 37 (11): 3197–207.
doi :
10.1002/eji.200737052 .
PMID
17948262 .
S2CID
25376411 .
Iovannisci D, Illek B, Fischer H (2010).
"Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T" . J. Gen. Physiol . 136 (1): 35–46.
doi :
10.1085/jgp.200910379 .
PMC
2894549 .
PMID
20548053 .
Clark HF, Gurney AL, Abaya E, et al. (2003).
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment" . Genome Res . 13 (10): 2265–70.
doi :
10.1101/gr.1293003 .
PMC
403697 .
PMID
12975309 .
Musset B, Cherny VV, Morgan D, et al. (2008).
"Detailed comparison of expressed and native voltage-gated proton channel currents" . J. Physiol . 586 (10): 2477–86.
doi :
10.1113/jphysiol.2007.149427 .
PMC
2464343 .
PMID
18356202 .
Strausberg RL, Feingold EA, Grouse LH, et al. (2002).
"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903.
Bibcode :
2002PNAS...9916899M .
doi :
10.1073/pnas.242603899 .
PMC
139241 .
PMID
12477932 .
Ramsey IS, Moran MM, Chong JA, Clapham DE (2006).
"A voltage-gated proton-selective channel lacking the pore domain" . Nature . 440 (7088): 1213–6.
Bibcode :
2006Natur.440.1213R .
doi :
10.1038/nature04700 .
PMC
4084761 .
PMID
16554753 .
Sakata S, Kurokawa T, Nørholm MH, et al. (2010).
"Functionality of the voltage-gated proton channel truncated in S4" . Proc. Natl. Acad. Sci. U.S.A . 107 (5): 2313–8.
Bibcode :
2010PNAS..107.2313S .
doi :
10.1073/pnas.0911868107 .
PMC
2836681 .
PMID
20018719 .