HVCN1

HVCN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A2A
Identifiers
Aliases	HVCN1 , HV1, VSOP, hydrogen voltage gated channel 1
External IDs	OMIM: 611227; MGI: 1921346; HomoloGene: 12535; GeneCards: HVCN1; OMA:HVCN1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12q24.11 Start 110,627,841 bp [1] End 110,704,950 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 F Start 122,344,867 bp [2] End 122,380,360 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in white blood cell monocyte granulocyte lymph node mucosa of ileum blood left testis spleen right testis appendix Top expressed in mesenteric lymph nodes granulocyte spleen blood zygote secondary oocyte subcutaneous adipose tissue tibiofemoral joint bone marrow primary oocyte More reference expression data BioGPS n/a
Gene ontology Molecular function ion channel activity voltage-gated cation channel activity voltage-gated ion channel activity voltage-gated proton channel activity identical protein binding Cellular component membrane integral component of membrane plasma membrane secretory granule membrane specific granule membrane integral component of plasma membrane phagocytic vesicle membrane Biological process transmembrane transport regulation of ion transmembrane transport cellular response to pH response to zinc ion ion transport cellular response to zinc ion sperm-egg recognition response to pH neutrophil degranulation proton transmembrane transport cell redox homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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.

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. GRCh38: Ensembl release 89: ENSG00000122986 – Ensembl, May 2017
2. 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. 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. 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

• 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.