HVCN1_MOUSE
ID HVCN1_MOUSE Reviewed; 269 AA.
AC Q3U2S8; Q9DCE4;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Voltage-gated hydrogen channel 1;
DE AltName: Full=Hydrogen voltage-gated channel 1;
DE Short=HV1;
DE AltName: Full=Voltage sensor domain-only protein;
DE Short=mVSOP;
GN Name=Hvcn1; Synonyms=Bts, Vsop;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ARG-201 AND ARG-207.
RX PubMed=16556803; DOI=10.1126/science.1122352;
RA Sasaki M., Takagi M., Okamura Y.;
RT "A voltage sensor-domain protein is a voltage-gated proton channel.";
RL Science 312:589-592(2006).
RN [4]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=19805063; DOI=10.1073/pnas.0905565106;
RA Morgan D., Capasso M., Musset B., Cherny V.V., Rios E., Dyer M.J.,
RA DeCoursey T.E.;
RT "Voltage-gated proton channels maintain pH in human neutrophils during
RT phagocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18022-18027(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 220-266, SUBUNIT, FUNCTION,
RP SUBCELLULAR LOCATION, COILED COIL, MUTAGENESIS OF ASN-231; 216-VAL--THR-218
RP AND 230-ILE--ILE-232, AND ACTIVITY REGULATION.
RX PubMed=22569364; DOI=10.1038/ncomms1823;
RA Fujiwara Y., Kurokawa T., Takeshita K., Kobayashi M., Okochi Y.,
RA Nakagawa A., Okamura Y.;
RT "The cytoplasmic coiled-coil mediates cooperative gating temperature
RT sensitivity in the voltage-gated H(+) channel Hv1.";
RL Nat. Commun. 3:816-816(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 220-269, SUBUNIT, SUBCELLULAR
RP LOCATION, FUNCTION, AND COILED COIL.
RX PubMed=23165764; DOI=10.1113/jphysiol.2012.243006;
RA Fujiwara Y., Kurokawa T., Takeshita K., Nakagawa A., Larsson H.P.,
RA Okamura Y.;
RT "Gating of the designed trimeric/tetrameric voltage-gated H+ channel.";
RL J. Physiol. (Lond.) 591:627-640(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 73-215, FUNCTION, SUBCELLULAR
RP LOCATION, TOPOLOGY, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=24584463; DOI=10.1038/nsmb.2783;
RA Takeshita K., Sakata S., Yamashita E., Fujiwara Y., Kawanabe A.,
RA Kurokawa T., Okochi Y., Matsuda M., Narita H., Okamura Y., Nakagawa A.;
RT "X-ray crystal structure of voltage-gated proton channel.";
RL Nat. Struct. Mol. Biol. 21:352-357(2014).
CC -!- FUNCTION: Mediates the voltage-dependent proton permeability of
CC excitable membranes. Forms a proton-selective channel through which
CC protons may pass in accordance with their electrochemical gradient.
CC Proton efflux, accompanied by membrane depolarization, facilitates
CC acute production of reactive oxygen species in phagocytosis.
CC {ECO:0000269|PubMed:16556803, ECO:0000269|PubMed:19805063,
CC ECO:0000269|PubMed:22569364, ECO:0000269|PubMed:23165764,
CC ECO:0000269|PubMed:24584463}.
CC -!- ACTIVITY REGULATION: The dimers display cooperative channel gating. The
CC channel activity is inhibited by zinc ions.
CC {ECO:0000269|PubMed:16556803, ECO:0000269|PubMed:19805063,
CC ECO:0000269|PubMed:22569364, ECO:0000269|PubMed:24584463}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22569364,
CC ECO:0000269|PubMed:23165764, ECO:0000269|PubMed:24584463}.
CC -!- INTERACTION:
CC Q3U2S8; Q3U2S8: Hvcn1; NbExp=3; IntAct=EBI-8401579, EBI-8401579;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Enriched in immune tissues, such as bone marrow,
CC macrophages and spleen. {ECO:0000269|PubMed:16556803}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Unlike other voltage-gated ion channels it lacks the
CC pore domain. {ECO:0000269|PubMed:16556803}.
CC -!- DOMAIN: The C-terminal coiled coil region mediates homodimerization and
CC cooperative channel gating. It is essential for normal subcellular
CC localization. {ECO:0000269|PubMed:16556803}.
CC -!- PTM: Phosphorylation may enhance channel gating. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the hydrogen channel family. {ECO:0000305}.
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DR EMBL; AK002854; BAB22409.1; -; mRNA.
DR EMBL; AK154880; BAE32899.1; -; mRNA.
DR EMBL; AK155123; BAE33062.1; -; mRNA.
DR EMBL; AK170422; BAE41787.1; -; mRNA.
DR EMBL; BC021548; AAH21548.1; -; mRNA.
DR CCDS; CCDS19644.1; -.
DR RefSeq; NP_001035954.1; NM_001042489.2.
DR RefSeq; NP_083028.1; NM_028752.3.
DR RefSeq; XP_006530535.1; XM_006530472.2.
DR RefSeq; XP_006530536.1; XM_006530473.1.
DR PDB; 3VMX; X-ray; 1.45 A; A/B/C/D=220-266.
DR PDB; 3VMY; X-ray; 1.47 A; A/B/C/D=220-269.
DR PDB; 3VMZ; X-ray; 1.55 A; A/B/C/D=220-269.
DR PDB; 3VN0; X-ray; 1.37 A; A/B/C/D=220-269.
DR PDB; 3VYI; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L=220-269.
DR PDB; 3WKV; X-ray; 3.45 A; A=73-215.
DR PDBsum; 3VMX; -.
DR PDBsum; 3VMY; -.
DR PDBsum; 3VMZ; -.
DR PDBsum; 3VN0; -.
DR PDBsum; 3VYI; -.
DR PDBsum; 3WKV; -.
DR AlphaFoldDB; Q3U2S8; -.
DR SMR; Q3U2S8; -.
DR BioGRID; 216489; 1.
DR DIP; DIP-46134N; -.
DR STRING; 10090.ENSMUSP00000072401; -.
DR TCDB; 1.A.51.1.1; the voltage-gated proton channel (vpc) family.
DR iPTMnet; Q3U2S8; -.
DR PhosphoSitePlus; Q3U2S8; -.
DR EPD; Q3U2S8; -.
DR MaxQB; Q3U2S8; -.
DR PaxDb; Q3U2S8; -.
DR PRIDE; Q3U2S8; -.
DR ProteomicsDB; 273325; -.
DR TopDownProteomics; Q3U2S8; -.
DR Antibodypedia; 31051; 163 antibodies from 29 providers.
DR DNASU; 74096; -.
DR Ensembl; ENSMUST00000072602; ENSMUSP00000072401; ENSMUSG00000064267.
DR Ensembl; ENSMUST00000100747; ENSMUSP00000098312; ENSMUSG00000064267.
DR GeneID; 74096; -.
DR KEGG; mmu:74096; -.
DR UCSC; uc008zku.2; mouse.
DR CTD; 84329; -.
DR MGI; MGI:1921346; Hvcn1.
DR VEuPathDB; HostDB:ENSMUSG00000064267; -.
DR eggNOG; ENOG502RX8B; Eukaryota.
DR GeneTree; ENSGT00940000159403; -.
DR HOGENOM; CLU_076372_0_0_1; -.
DR InParanoid; Q3U2S8; -.
DR OMA; HLEFSCT; -.
DR OrthoDB; 1601156at2759; -.
DR PhylomeDB; Q3U2S8; -.
DR TreeFam; TF332056; -.
DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 74096; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Hvcn1; mouse.
DR PRO; PR:Q3U2S8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q3U2S8; protein.
DR Bgee; ENSMUSG00000064267; Expressed in mesenteric lymph node and 105 other tissues.
DR ExpressionAtlas; Q3U2S8; baseline and differential.
DR Genevisible; Q3U2S8; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0022843; F:voltage-gated cation channel activity; ISO:MGI.
DR GO; GO:0030171; F:voltage-gated proton channel activity; IDA:HGNC-UCL.
DR GO; GO:0071467; P:cellular response to pH; ISS:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; ISS:UniProtKB.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:MGI.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:HGNC-UCL.
DR GO; GO:0051453; P:regulation of intracellular pH; ISO:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0009268; P:response to pH; IDA:HGNC-UCL.
DR GO; GO:0010043; P:response to zinc ion; IDA:HGNC-UCL.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR031846; Hvcn1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR031844; VGPC1_C.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46480; PTHR46480; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF16799; VGPC1_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..269
FT /note="Voltage-gated hydrogen channel 1"
FT /id="PRO_0000342188"
FT TOPO_DOM 1..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical; Name=Segment S1"
FT TOPO_DOM 118..134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..157
FT /note="Helical; Name=Segment S2"
FT TOPO_DOM 158..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical; Name=Segment S3"
FT TOPO_DOM 187..193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical; Name=Segment S4"
FT TOPO_DOM 215..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 46..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 221..261
FT /evidence="ECO:0000269|PubMed:22569364,
FT ECO:0000269|PubMed:23165764"
FT MUTAGEN 201
FT /note="R->Q: Faster channel activation kinetics."
FT /evidence="ECO:0000269|PubMed:16556803"
FT MUTAGEN 207
FT /note="R->Q: Same activation kinetics as wild-type."
FT /evidence="ECO:0000269|PubMed:16556803"
FT MUTAGEN 216..218
FT /note="VKT->GGG: Impairs gating cooperativity."
FT /evidence="ECO:0000269|PubMed:22569364"
FT MUTAGEN 230..232
FT /note="INI->NIN: Slows channel activation."
FT /evidence="ECO:0000269|PubMed:22569364"
FT MUTAGEN 231
FT /note="N->L: No effect on channel activation kinetics."
FT /evidence="ECO:0000269|PubMed:22569364"
FT CONFLICT 66
FT /note="E -> A (in Ref. 1; BAE33062)"
FT /evidence="ECO:0000305"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:3WKV"
FT HELIX 96..120
FT /evidence="ECO:0007829|PDB:3WKV"
FT HELIX 134..155
FT /evidence="ECO:0007829|PDB:3WKV"
FT HELIX 164..184
FT /evidence="ECO:0007829|PDB:3WKV"
FT HELIX 220..261
FT /evidence="ECO:0007829|PDB:3VN0"
SQ SEQUENCE 269 AA; 31242 MW; B549CB553DEB6568 CRC64;
MTSHDPKAVT RRTKVAPTKR MSRFLKHFTV VGDDYHTWNV NYKKWENEEE EEEPAPTSAE
GEGNAEGPDA EAGSASTPRQ SLDFRSRLRK LFSSHRFQVI IICLVVLDAL LVLAELLLDL
KIIEPDEQDY AVTAFHYMSF AILVFFMLEI FFKIFVFRLE FFHHKFEILD AFVVVVSFVL
DLVLLFKSHH FEALGLLILL RLWRVARIIN GIIISVKTRS ERQILRLKQI NIQLATKIQH
LEFSCSEKEQ EIERLNKLLK QNGLLGDVN
