HVCN1

Last updated
HVCN1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HVCN1 , HV1, VSOP, hydrogen voltage gated channel 1
External IDs OMIM: 611227 MGI: 1921346 HomoloGene: 12535 GeneCards: HVCN1
Orthologs
SpeciesHumanMouse
Entrez

84329

74096

Ensembl

ENSG00000122986

ENSMUSG00000064267

UniProt

Q96D96

Q3U2S8

RefSeq (mRNA)

NM_001040107
NM_001256413
NM_032369

NM_001042489
NM_028752
NM_001359454

RefSeq (protein)

NP_001035196
NP_001243342
NP_115745

NP_001035954
NP_083028
NP_001346383

Location (UCSC) Chr 12: 110.63 – 110.7 Mb Chr 5: 122.34 – 122.38 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Potassium channel</span> Ion channel that selectively passes K+

Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.

<span class="mw-page-title-main">Voltage-gated ion channel</span> Type of ion channel transmembrane protein

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels.

<span class="mw-page-title-main">Kv1.1</span>

Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel that in humans is encoded by the KCNA1 gene. Isaacs syndrome is a result of an autoimmune reaction against the Kv1.1 ion channel.

<span class="mw-page-title-main">SCN4B</span> Protein-coding gene in the species Homo sapiens

Sodium channel β-subunit4, also known as SCN4B or Naβ4, is an auxiliary sodium channel subunit that can alter the kinetics of sodium channels. The protein is encoded by the SCN4B gene. Mutations in the SCN4B are associated with long QT syndrome.

<span class="mw-page-title-main">KvLQT3</span> Protein-coding gene in the species Homo sapiens

Kv7.3 (KvLQT3) is a potassium channel protein coded for by the gene KCNQ3.

Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.

<span class="mw-page-title-main">KCND2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNK2</span> Protein-coding gene in the species Homo sapiens

Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.

<span class="mw-page-title-main">SCN3B</span> Protein-coding gene in the species Homo sapiens

Sodium channel subunit beta-3 is a protein that in humans is encoded by the SCN3B gene. Two alternatively spliced variants, encoding the same protein, have been identified.

<span class="mw-page-title-main">KCNAB1</span> Protein-coding gene in the species Homo sapiens

Voltage-gated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNAB1 gene.

<span class="mw-page-title-main">KCNMB2</span> Protein-coding gene in the species Homo sapiens

Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.

<span class="mw-page-title-main">KCNIP1</span> Protein-coding gene in the species Homo sapiens

Kv channel-interacting protein 1 also known as KChIP1 is a protein that in humans is encoded by the KCNIP1 gene.

<span class="mw-page-title-main">KCNQ5</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily KQT member 5 is a protein that in humans is encoded by the KCNQ5 gene.

<span class="mw-page-title-main">KCNC4</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel, Shaw-related subfamily, member 4 (KCNC4), also known as Kv3.4, is a human gene.

<span class="mw-page-title-main">SCN2B</span> Protein-coding gene in the species Homo sapiens

Sodium channel subunit beta-2 is a protein that in humans is encoded by the SCN2B gene.

<span class="mw-page-title-main">KCND1</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel, Shal-related subfamily, member 1 (KCND1), also known as Kv4.1, is a human gene.

<span class="mw-page-title-main">KCNIP4</span> Protein-coding gene in the species Homo sapiens

Kv channel-interacting protein 4 is a protein that in humans is encoded by the KCNIP4 gene.

<span class="mw-page-title-main">CatSper1</span> Protein-coding gene in the species Homo sapiens

CatSper1, is a protein which in humans is encoded by the CATSPER1 gene. CatSper1 is a member of the cation channels of sperm family of protein. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.

<span class="mw-page-title-main">CatSper2</span> Protein-coding gene in the species Homo sapiens

CatSper2, is a protein which in humans is encoded by the CATSPER2 gene. CatSper2 is a member of the cation channels of sperm family of protein. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000122986 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000064267 - 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. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.