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Q96D96 (HVCN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Voltage-gated hydrogen channel 1
Alternative name(s):
Hydrogen voltage-gated channel 1
Short name=HV1
Voltage sensor domain-only protein
Gene names
Name:HVCN1
Synonyms:VSOP
ORF Names:UNQ578/PRO1140
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length273 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient. Proton efflux, accompanied by membrane depolarization, facilitates acute production of reactive oxygen species in phagocytosis. Ref.6 Ref.7 Ref.8

Enzyme regulation

The dimers display cooperative channel gating By similarity. The channel activity is inhibited by zinc ions. Ref.6 Ref.8

Subunit structure

Homodimer. Ref.9

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note: Detected mainly at intracellular membranes upon overexpression in HeLa cells (PuMed:20147290), but not in other cell types. Ref.6 Ref.7 Ref.8 Ref.9

Tissue specificity

Enriched in immune tissues, such as lymph nodes, B-lymphocytes, monocytes and spleen. Ref.6

Domain

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain. Ref.9

The C-terminal coiled coil region mediates homodimerization and cooperative channel gating. It is essential for normal subcellular localization. Ref.9

Post-translational modification

Phosphorylation may enhance channel gating.

Sequence similarities

Belongs to the hydrogen channel family.

Sequence caution

The sequence AAQ89413.1 differs from that shown. Reason: Frameshift at positions 164 and 175.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96D96-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96D96-2)

The sequence of this isoform differs from the canonical sequence as follows:
     66-102: Missing.
Isoform 3 (identifier: Q96D96-3)

The sequence of this isoform differs from the canonical sequence as follows:
     253-273: EQEIERLNKLLRQHGLLGEVN → PLD
Note: No experimental confirmation available.
Isoform 4 (identifier: Q96D96-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 273273Voltage-gated hydrogen channel 1
PRO_0000342187

Regions

Topological domain1 – 100100Cytoplasmic By similarity
Transmembrane101 – 12121Helical; Name=Segment S1; By similarity
Topological domain122 – 13817Extracellular By similarity
Transmembrane139 – 16123Helical; Name=Segment S2; By similarity
Topological domain162 – 1698Cytoplasmic By similarity
Transmembrane170 – 19021Helical; Name=Segment S3; By similarity
Topological domain191 – 1977Extracellular By similarity
Transmembrane198 – 21821Helical; Name=Segment S4; By similarity
Topological domain219 – 27355Cytoplasmic By similarity
Coiled coil223 – 26644 Ref.9
Compositional bias46 – 5510Poly-Glu
Compositional bias176 – 1805Poly-Val

Amino acid modifications

Modified residue291Phosphothreonine Probable
Modified residue971Phosphoserine Probable

Natural variations

Alternative sequence1 – 2020Missing in isoform 4.
VSP_045052
Alternative sequence66 – 10237Missing in isoform 2.
VSP_034395
Alternative sequence253 – 27321EQEIE…LGEVN → PLD in isoform 3.
VSP_034396

Experimental info

Mutagenesis291T → A: Loss of a phosphorylation site. Reduces phosphorylation. Ref.7
Mutagenesis971S → A: Loss of a phosphorylation site. Strongly reduces phosphorylation. Ref.7
Mutagenesis1121D → A, F, N or S: Alters channel selectivity. Converts the proton channel to an anion channel. Ref.8
Mutagenesis1121D → E: No effect on channel activity and proton selectivity. Ref.8
Mutagenesis1121D → V: Abolishes channel activity. Ref.8
Mutagenesis1401H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-193. Ref.6 Ref.8
Mutagenesis1931H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-140. Ref.6 Ref.8
Mutagenesis2051R → A: Faster channel activation and deactivation kinetics. Ref.6
Mutagenesis2081R → A: Faster channel activation and deactivation kinetics. Ref.6
Mutagenesis2111R → A: Faster channel deactivation kinetics. Ref.6
Sequence conflict1651F → Y in BAG57024. Ref.2

Secondary structure

... 273
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 0F93B428AECBBC4F

FASTA27331,683
        10         20         30         40         50         60 
MATWDEKAVT RRAKVAPAER MSKFLRHFTV VGDDYHAWNI NYKKWENEEE EEEEEQPPPT 

        70         80         90        100        110        120 
PVSGEEGRAA APDVAPAPGP APRAPLDFRG MLRKLFSSHR FQVIIICLVV LDALLVLAEL 

       130        140        150        160        170        180 
ILDLKIIQPD KNNYAAMVFH YMSITILVFF MMEIIFKLFV FRLEFFHHKF EILDAVVVVV 

       190        200        210        220        230        240 
SFILDIVLLF QEHQFEALGL LILLRLWRVA RIINGIIISV KTRSERQLLR LKQMNVQLAA 

       250        260        270 
KIQHLEFSCS EKEQEIERLN KLLRQHGLLG EVN 

« Hide

Isoform 2 [UniParc].

Checksum: 1AD13F7D49A62C4D
Show »

FASTA23627,713
Isoform 3 [UniParc].

Checksum: 092B095DD219550A
Show »

FASTA25529,538
Isoform 4 [UniParc].

Checksum: F1349C26BCC164F1
Show »

FASTA25329,415

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Cerebellum.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Eye, Lung and Testis.
[6]"A voltage-gated proton-selective channel lacking the pore domain."
Ramsey I.S., Moran M.M., Chong J.A., Clapham D.E.
Nature 440:1213-1216(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, MUTAGENESIS OF HIS-140; HIS-193; ARG-205; ARG-208 AND ARG-211.
[7]"Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes."
Musset B., Capasso M., Cherny V.V., Morgan D., Bhamrah M., Dyer M.J., DeCoursey T.E.
J. Biol. Chem. 285:5117-5121(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-29 AND SER-97, MUTAGENESIS OF THR-29 AND SER-97, FUNCTION, SUBCELLULAR LOCATION.
[8]"Aspartate 112 is the selectivity filter of the human voltage-gated proton channel."
Musset B., Smith S.M., Rajan S., Morgan D., Cherny V.V., Decoursey T.E.
Nature 480:273-277(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-112; HIS-140 AND HIS-193, SUBCELLULAR LOCATION, ENZYME REGULATION.
[9]"The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1."
Li S.J., Zhao Q., Zhou Q., Unno H., Zhai Y., Sun F.
J. Biol. Chem. 285:12047-12054(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 221-273, SUBUNIT, SUBCELLULAR LOCATION, COILED COIL, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY359054 mRNA. Translation: AAQ89413.1. Frameshift.
AK293543 mRNA. Translation: BAG57024.1.
AC144522 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97935.1.
CH471054 Genomic DNA. Translation: EAW97936.1.
BC007277 mRNA. Translation: AAH07277.1.
BC009731 mRNA. Translation: AAH09731.1.
BC032672 mRNA. Translation: AAH32672.1.
CCDSCCDS31900.1. [Q96D96-1]
CCDS58278.1. [Q96D96-4]
RefSeqNP_001035196.1. NM_001040107.1. [Q96D96-1]
NP_001243342.1. NM_001256413.1. [Q96D96-4]
NP_115745.2. NM_032369.3. [Q96D96-1]
XP_005254005.1. XM_005253948.1. [Q96D96-1]
XP_005254006.1. XM_005253949.1. [Q96D96-2]
XP_006719703.1. XM_006719640.1. [Q96D96-1]
UniGeneHs.211511.
Hs.334637.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3A2AX-ray2.00A/B/C/D221-273[»]
ProteinModelPortalQ96D96.
SMRQ96D96. Positions 88-266.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124053. 1 interaction.
DIPDIP-46112N.
MINTMINT-4724965.
STRING9606.ENSP00000349181.

Chemistry

GuidetoPHARMACOLOGY746.

Protein family/group databases

TCDB1.A.51.1.2. the voltage-gated proton channel (vpc) family.

PTM databases

PhosphoSiteQ96D96.

Polymorphism databases

DMDM74751810.

Proteomic databases

MaxQBQ96D96.
PaxDbQ96D96.
PRIDEQ96D96.

Protocols and materials databases

DNASU84329.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000242607; ENSP00000242607; ENSG00000122986. [Q96D96-1]
ENST00000356742; ENSP00000349181; ENSG00000122986. [Q96D96-1]
ENST00000439744; ENSP00000412052; ENSG00000122986. [Q96D96-4]
ENST00000548312; ENSP00000449601; ENSG00000122986. [Q96D96-3]
GeneID84329.
KEGGhsa:84329.
UCSCuc001trq.1. human. [Q96D96-3]
uc001trs.2. human. [Q96D96-1]

Organism-specific databases

CTD84329.
GeneCardsGC12M111086.
H-InvDBHIX0011039.
HGNCHGNC:28240. HVCN1.
HPAHPA039329.
MIM611227. gene.
neXtProtNX_Q96D96.
PharmGKBPA144596422.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46709.
HOGENOMHOG000067871.
HOVERGENHBG102207.
InParanoidQ96D96.
OMAEFSCSEK.
OrthoDBEOG789CDV.
PhylomeDBQ96D96.
TreeFamTF332056.

Enzyme and pathway databases

ReactomeREACT_163848. Reproduction.

Gene expression databases

ArrayExpressQ96D96.
BgeeQ96D96.
CleanExHS_HVCN1.
GenevestigatorQ96D96.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHVCN1. human.
GeneWikiHVCN1.
GenomeRNAi84329.
NextBio74079.
PROQ96D96.
SOURCESearch...

Entry information

Entry nameHVCN1_HUMAN
AccessionPrimary (citable) accession number: Q96D96
Secondary accession number(s): A8MQ37 expand/collapse secondary AC list , B4DEB3, F8WCH5, Q6UW11, Q96IS5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM