HVCN1

HVCN1
Available structures
PDB	Ortholog search:PDBeRCSB
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)
End	110,704,950bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	122,380,360bp
RNA expressionpattern
	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
	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
	84329
	74096
	ENSG00000122986
	ENSMUSG00000064267
	Q96D96
	Q3U2S8
	NM_001040107; NM_001256413; NM_032369
	NM_001042489; NM_028752; NM_001359454
	NP_001035196; NP_001243342; NP_115745
	NP_001035954; NP_083028; NP_001346383
	Wikidata
View/Edit Human	View/Edit Mouse

Voltage-gated hydrogen channel 1is aproteinthat in humans is encoded by theHVCN1gene.

Voltage-gated hydrogen channel 1 is avoltage-gated proton channelthat has been shown to allow proton transport intophagosomes^[5]^[6]and out of many types of cells includingspermatozoa,electrically excitablecells andrespiratory epithelialcells.^[7]The proton-conducting HVCN1 channel has only transmembrane domains corresponding to the S1-S4 voltage sensing domains (VSD) ofvoltage-gated potassium channelsandvoltage-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 moleculeinhibitors of the HVCN1 channel are being developed aschemotherapeuticsandanti-inflammatoryagents.^[16]

References

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000122986–Ensembl,May 2017
^^a ^b ^cGRCm38: 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.PMC3030552.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.PMC3014425.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.PMC2778278.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.PMC3245885.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.PMC4035905.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.PMC3237871.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.PMC4429351.PMID 25955978.
^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.PMC2935852.PMID 20023639.
^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.PMC2925041.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.PMC2655391.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.PMC3559007.PMID 23352164.

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.PMC2852942.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.PMC3025757.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.PMC1356129.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.PMC2820736.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.PMC2990768.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.PMC2409406.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.PMC515316.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.PMC2650464.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.PMC2894549.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.PMC403697.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.PMC2464343.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.PMC139241.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.PMC4084761.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.PMC2836681.PMID 20018719.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000122986–Ensembl,May 2017

[refGRCm38Ensembl-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.

[pmid16483534-5] 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.

[pmid20139987-6] 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.PMC3030552.PMID 20139987.

[pmid20961760-7] 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.PMC3014425.PMID 20961760.

[pmid19233200-8] 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.PMC2778278.PMID 19233200.

[pmid21843503-9] 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.PMC3245885.PMID 21843503.

[pmid20543828-10] 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.PMC4035905.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.PMC3237871.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.PMC4429351.PMID 25955978.

[pmid20023639-13] 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.PMC2935852.PMID 20023639.

[pmid20023640-14] 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.PMC2925041.PMID 20023640.

[pmid18801839-15] DeCoursey TE (November 2008)."Voltage-gated proton channels: what's next?".J. Physiol.586(Pt 22): 5305–24.doi:10.1113/jphysiol.2008.161703.PMC2655391.PMID 18801839.

[pmid23352164-16] 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.PMC3559007.PMID 23352164.

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As a drug target

References

Further reading