HVCN1_HUMAN
ID HVCN1_HUMAN Reviewed; 273 AA.
AC Q96D96; A8MQ37; B4DEB3; F8WCH5; Q6UW11; Q96IS5;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
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;
GN Name=HVCN1; Synonyms=VSOP; ORFNames=UNQ578/PRO1140;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, Lung, and Testis;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ACTIVITY REGULATION,
RP AND MUTAGENESIS OF HIS-140; HIS-193; ARG-205; ARG-208 AND ARG-211.
RX PubMed=16554753; DOI=10.1038/nature04700;
RA Ramsey I.S., Moran M.M., Chong J.A., Clapham D.E.;
RT "A voltage-gated proton-selective channel lacking the pore domain.";
RL Nature 440:1213-1216(2006).
RN [7]
RP PHOSPHORYLATION AT THR-29 AND SER-97, MUTAGENESIS OF THR-29 AND SER-97,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20037153; DOI=10.1074/jbc.c109.082727;
RA Musset B., Capasso M., Cherny V.V., Morgan D., Bhamrah M., Dyer M.J.,
RA DeCoursey T.E.;
RT "Identification of Thr29 as a critical phosphorylation site that activates
RT the human proton channel Hvcn1 in leukocytes.";
RL J. Biol. Chem. 285:5117-5121(2010).
RN [8]
RP FUNCTION, MUTAGENESIS OF ASP-112; HIS-140 AND HIS-193, SUBCELLULAR
RP LOCATION, AND ACTIVITY REGULATION.
RX PubMed=22020278; DOI=10.1038/nature10557;
RA Musset B., Smith S.M., Rajan S., Morgan D., Cherny V.V., Decoursey T.E.;
RT "Aspartate 112 is the selectivity filter of the human voltage-gated proton
RT channel.";
RL Nature 480:273-277(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 221-273, SUBUNIT, SUBCELLULAR
RP LOCATION, COILED COIL, AND DOMAIN.
RX PubMed=20147290; DOI=10.1074/jbc.m109.040360;
RA Li S.J., Zhao Q., Zhou Q., Unno H., Zhai Y., Sun F.;
RT "The role and structure of the carboxyl-terminal domain of the human
RT voltage-gated proton channel Hv1.";
RL J. Biol. Chem. 285:12047-12054(2010).
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:16554753, ECO:0000269|PubMed:20037153,
CC ECO:0000269|PubMed:22020278}.
CC -!- ACTIVITY REGULATION: The dimers display cooperative channel gating (By
CC similarity). The channel activity is inhibited by zinc ions.
CC {ECO:0000250, ECO:0000269|PubMed:16554753,
CC ECO:0000269|PubMed:22020278}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20147290}.
CC -!- INTERACTION:
CC Q96D96; Q96D96: HVCN1; NbExp=2; IntAct=EBI-15704959, EBI-15704959;
CC Q96D96-2; Q92876: KLK6; NbExp=3; IntAct=EBI-25888137, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC membrane; Multi-pass membrane protein. Note=Detected mainly at
CC intracellular membranes upon overexpression in HeLa cells
CC (PuMed:20147290), but not in other cell types.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96D96-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96D96-2; Sequence=VSP_034395;
CC Name=3;
CC IsoId=Q96D96-3; Sequence=VSP_034396;
CC Name=4;
CC IsoId=Q96D96-4; Sequence=VSP_045052;
CC -!- TISSUE SPECIFICITY: Enriched in immune tissues, such as lymph nodes, B-
CC lymphocytes, monocytes and spleen. {ECO:0000269|PubMed:16554753}.
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:20147290}.
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:20147290}.
CC -!- PTM: Phosphorylation may enhance channel gating.
CC {ECO:0000269|PubMed:20037153}.
CC -!- SIMILARITY: Belongs to the hydrogen channel family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89413.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY359054; AAQ89413.1; ALT_FRAME; mRNA.
DR EMBL; AK293543; BAG57024.1; -; mRNA.
DR EMBL; AC144522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97935.1; -; Genomic_DNA.
DR EMBL; CH471054; EAW97936.1; -; Genomic_DNA.
DR EMBL; BC007277; AAH07277.1; -; mRNA.
DR EMBL; BC009731; AAH09731.1; -; mRNA.
DR EMBL; BC032672; AAH32672.1; -; mRNA.
DR CCDS; CCDS31900.1; -. [Q96D96-1]
DR CCDS; CCDS58278.1; -. [Q96D96-4]
DR RefSeq; NP_001035196.1; NM_001040107.1. [Q96D96-1]
DR RefSeq; NP_001243342.1; NM_001256413.1. [Q96D96-4]
DR RefSeq; NP_115745.2; NM_032369.3. [Q96D96-1]
DR RefSeq; XP_005254005.1; XM_005253948.2. [Q96D96-1]
DR RefSeq; XP_011537147.1; XM_011538845.1. [Q96D96-1]
DR RefSeq; XP_011537148.1; XM_011538846.2. [Q96D96-1]
DR RefSeq; XP_011537149.1; XM_011538847.1. [Q96D96-1]
DR RefSeq; XP_016875516.1; XM_017020027.1. [Q96D96-1]
DR PDB; 3A2A; X-ray; 2.00 A; A/B/C/D=221-273.
DR PDB; 5OQK; NMR; -; A=83-226.
DR PDBsum; 3A2A; -.
DR PDBsum; 5OQK; -.
DR AlphaFoldDB; Q96D96; -.
DR SMR; Q96D96; -.
DR BioGRID; 124053; 29.
DR DIP; DIP-46112N; -.
DR IntAct; Q96D96; 8.
DR STRING; 9606.ENSP00000349181; -.
DR GuidetoPHARMACOLOGY; 746; -.
DR TCDB; 1.A.51.1.2; the voltage-gated proton channel (vpc) family.
DR iPTMnet; Q96D96; -.
DR PhosphoSitePlus; Q96D96; -.
DR BioMuta; HVCN1; -.
DR DMDM; 74751810; -.
DR EPD; Q96D96; -.
DR jPOST; Q96D96; -.
DR MassIVE; Q96D96; -.
DR MaxQB; Q96D96; -.
DR PaxDb; Q96D96; -.
DR PeptideAtlas; Q96D96; -.
DR PRIDE; Q96D96; -.
DR ProteomicsDB; 31154; -.
DR ProteomicsDB; 76259; -. [Q96D96-1]
DR ProteomicsDB; 76260; -. [Q96D96-2]
DR ProteomicsDB; 76261; -. [Q96D96-3]
DR Antibodypedia; 31051; 163 antibodies from 29 providers.
DR DNASU; 84329; -.
DR Ensembl; ENST00000242607.13; ENSP00000242607.8; ENSG00000122986.14. [Q96D96-1]
DR Ensembl; ENST00000356742.9; ENSP00000349181.5; ENSG00000122986.14. [Q96D96-1]
DR Ensembl; ENST00000439744.6; ENSP00000412052.2; ENSG00000122986.14. [Q96D96-4]
DR Ensembl; ENST00000548312.5; ENSP00000449601.1; ENSG00000122986.14. [Q96D96-3]
DR Ensembl; ENST00000620084.4; ENSP00000479812.1; ENSG00000122986.14. [Q96D96-1]
DR GeneID; 84329; -.
DR KEGG; hsa:84329; -.
DR MANE-Select; ENST00000242607.13; ENSP00000242607.8; NM_032369.4; NP_115745.2.
DR UCSC; uc001trq.1; human. [Q96D96-1]
DR CTD; 84329; -.
DR DisGeNET; 84329; -.
DR GeneCards; HVCN1; -.
DR HGNC; HGNC:28240; HVCN1.
DR HPA; ENSG00000122986; Tissue enhanced (choroid plexus, lymphoid tissue).
DR MIM; 611227; gene.
DR neXtProt; NX_Q96D96; -.
DR OpenTargets; ENSG00000122986; -.
DR PharmGKB; PA144596422; -.
DR VEuPathDB; HostDB:ENSG00000122986; -.
DR eggNOG; ENOG502RX8B; Eukaryota.
DR GeneTree; ENSGT00940000159403; -.
DR HOGENOM; CLU_076372_0_0_1; -.
DR InParanoid; Q96D96; -.
DR OMA; HLEFSCT; -.
DR OrthoDB; 1601156at2759; -.
DR PhylomeDB; Q96D96; -.
DR TreeFam; TF332056; -.
DR PathwayCommons; Q96D96; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-1300642; Sperm Motility And Taxes.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q96D96; -.
DR BioGRID-ORCS; 84329; 13 hits in 1069 CRISPR screens.
DR ChiTaRS; HVCN1; human.
DR GeneWiki; HVCN1; -.
DR GenomeRNAi; 84329; -.
DR Pharos; Q96D96; Tchem.
DR PRO; PR:Q96D96; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96D96; protein.
DR Bgee; ENSG00000122986; Expressed in leukocyte and 171 other tissues.
DR ExpressionAtlas; Q96D96; baseline and differential.
DR Genevisible; Q96D96; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IDA:HGNC-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0022843; F:voltage-gated cation channel activity; EXP:Reactome.
DR GO; GO:0030171; F:voltage-gated proton channel activity; IDA:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome.
DR GO; GO:0071467; P:cellular response to pH; IDA:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; IDA:UniProtKB.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IEA:Ensembl.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; IEA:Ensembl.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0009268; P:response to pH; ISS: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; Alternative splicing; Cell membrane; Coiled coil;
KW Hydrogen ion transport; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..273
FT /note="Voltage-gated hydrogen channel 1"
FT /id="PRO_0000342187"
FT TOPO_DOM 1..100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 101..121
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 122..138
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 139..161
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 162..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 170..190
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 191..197
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 198..218
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 219..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 46..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 223..266
FT /evidence="ECO:0000269|PubMed:20147290"
FT MOD_RES 29
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:20037153"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:20037153"
FT VAR_SEQ 1..20
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045052"
FT VAR_SEQ 66..102
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034395"
FT VAR_SEQ 253..273
FT /note="EQEIERLNKLLRQHGLLGEVN -> PLD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_034396"
FT MUTAGEN 29
FT /note="T->A: Loss of a phosphorylation site. Reduces
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:20037153"
FT MUTAGEN 97
FT /note="S->A: Loss of a phosphorylation site. Strongly
FT reduces phosphorylation."
FT /evidence="ECO:0000269|PubMed:20037153"
FT MUTAGEN 112
FT /note="D->A,F,N,S: Alters channel selectivity. Converts the
FT proton channel to an anion channel."
FT /evidence="ECO:0000269|PubMed:22020278"
FT MUTAGEN 112
FT /note="D->E: No effect on channel activity and proton
FT selectivity."
FT /evidence="ECO:0000269|PubMed:22020278"
FT MUTAGEN 112
FT /note="D->V: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:22020278"
FT MUTAGEN 140
FT /note="H->A: Exhibits selectivity to protons but
FT sensitivity to zinc ions is abolished; when associated with
FT A-193."
FT /evidence="ECO:0000269|PubMed:16554753,
FT ECO:0000269|PubMed:22020278"
FT MUTAGEN 193
FT /note="H->A: Exhibits selectivity to protons but
FT sensitivity to zinc ions is abolished; when associated with
FT A-140."
FT /evidence="ECO:0000269|PubMed:16554753,
FT ECO:0000269|PubMed:22020278"
FT MUTAGEN 205
FT /note="R->A: Faster channel activation and deactivation
FT kinetics."
FT /evidence="ECO:0000269|PubMed:16554753"
FT MUTAGEN 208
FT /note="R->A: Faster channel activation and deactivation
FT kinetics."
FT /evidence="ECO:0000269|PubMed:16554753"
FT MUTAGEN 211
FT /note="R->A: Faster channel deactivation kinetics."
FT /evidence="ECO:0000269|PubMed:16554753"
FT CONFLICT 165
FT /note="F -> Y (in Ref. 2; BAG57024)"
FT /evidence="ECO:0000305"
FT HELIX 87..99
FT /evidence="ECO:0007829|PDB:5OQK"
FT HELIX 101..124
FT /evidence="ECO:0007829|PDB:5OQK"
FT HELIX 134..157
FT /evidence="ECO:0007829|PDB:5OQK"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:5OQK"
FT HELIX 169..189
FT /evidence="ECO:0007829|PDB:5OQK"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:5OQK"
FT HELIX 197..223
FT /evidence="ECO:0007829|PDB:5OQK"
FT HELIX 227..265
FT /evidence="ECO:0007829|PDB:3A2A"
SQ SEQUENCE 273 AA; 31683 MW; 0F93B428AECBBC4F CRC64;
MATWDEKAVT RRAKVAPAER MSKFLRHFTV VGDDYHAWNI NYKKWENEEE EEEEEQPPPT
PVSGEEGRAA APDVAPAPGP APRAPLDFRG MLRKLFSSHR FQVIIICLVV LDALLVLAEL
ILDLKIIQPD KNNYAAMVFH YMSITILVFF MMEIIFKLFV FRLEFFHHKF EILDAVVVVV
SFILDIVLLF QEHQFEALGL LILLRLWRVA RIINGIIISV KTRSERQLLR LKQMNVQLAA
KIQHLEFSCS EKEQEIERLN KLLRQHGLLG EVN
