HVCN1

HVCN1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHVCN1, HV1, VSOP, hydrogen voltage gated channel 1
External IDsOMIM: 611227; MGI: 1921346; HomoloGene: 12535; GeneCards: HVCN1; OMA:HVCN1 - orthologs
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 MbChr 5: 122.34 – 122.38 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000122986 – Ensembl, May 2017
  2. ^ a b c 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". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 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, 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.
  7. ^ 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.
  8. ^ 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.
  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". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1818 (2): 286–293. 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". Nature Structural & Molecular Biology. 17 (7): 869–875. 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): 273–277. 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, 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.
  13. ^ Gonzalez C, Koch HP, Drum BM, Larsson HP (January 2010). "Strong cooperativity between subunits in voltage-gated proton channels". Nature Structural & Molecular Biology. 17 (1): 51–56. 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". Nature Structural & Molecular Biology. 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?". The Journal of Physiology. 586 (22): 5305–5324. 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): 274–287. doi:10.1016/j.neuron.2012.11.013. PMC 3559007. PMID 23352164.

Further reading

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