HVCN1

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Hydrogen voltage-gated channel 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HVCN1 ; HV1; VSOP
External IDs OMIM611227 MGI1921346 HomoloGene12535 IUPHAR: Hv1 GeneCards: HVCN1 Gene
Orthologs
Species Human Mouse
Entrez 84329 74096
Ensembl ENSG00000122986 ENSMUSG00000064267
UniProt Q96D96 Q3U2S8
RefSeq (mRNA) NM_001040107 NM_001042489
RefSeq (protein) NP_001035196 NP_001035954
Location (UCSC) Chr 12:
111.07 – 111.14 Mb
Chr 5:
122.21 – 122.24 Mb
PubMed search [1] [2]

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 phagosomes12 and out of many types of cells including spermatozoa, electrically excitable cells and respiratory epithelial cells.3 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.4 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.56 The HVCN1 protein has been shown to exist as a dimer with two functioning pores.78 Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.9

As a drug target

Small molecule inhibitors of the HVCN1 channel are being developed as chemotherapeutics and anti-inflammatory agents.10

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. PMID 20543828. 
  7. ^ Gonzalez C, Koch HP, Drum BM, Larsson HP (January 2010). "Strong cooperativity between subunits in voltage-gated proton channels". Nat. Struct. Mol. Biol. 17 (1): 51–6. doi:10.1038/nsmb.1739. PMC 2935852. PMID 20023639. 
  8. ^ 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. 
  9. ^ DeCoursey TE (November 2008). "Voltage-gated proton channels: what's next?". J. Physiol. (Lond.) 586 (Pt 22): 5305–24. doi:10.1113/jphysiol.2008.161703. PMC 2655391. PMID 18801839. 
  10. ^ 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








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