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Protein

Voltage-gated hydrogen channel 1

Gene

HVCN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

Enzyme regulationi

The dimers display cooperative channel gating (By similarity). The channel activity is inhibited by zinc ions.By similarity2 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • voltage-gated cation channel activity Source: Reactome
  • voltage-gated proton channel activity Source: UniProtKB

GO - Biological processi

  • cellular response to pH Source: UniProtKB
  • cellular response to zinc ion Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • proton transmembrane transport Source: UniProtKB
  • regulation of ion transmembrane transport Source: UniProtKB-KW
  • response to pH Source: HGNC
  • response to zinc ion Source: HGNC
  • sperm-egg recognition Source: Reactome

Keywordsi

Molecular functionIon channel, Voltage-gated channel
Biological processHydrogen ion transport, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1300642 Sperm Motility And Taxes
R-HSA-6798695 Neutrophil degranulation

Protein family/group databases

TCDBi1.A.51.1.2 the voltage-gated proton channel (vpc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-gated hydrogen channel 1
Alternative name(s):
Hydrogen voltage-gated channel 1
Short name:
HV1
Voltage sensor domain-only protein
Gene namesi
Name:HVCN1
Synonyms:VSOP
ORF Names:UNQ578/PRO1140
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000122986.13
HGNCiHGNC:28240 HVCN1
MIMi611227 gene
neXtProtiNX_Q96D96

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 100CytoplasmicBy similarityAdd BLAST100
Transmembranei101 – 121Helical; Name=Segment S1By similarityAdd BLAST21
Topological domaini122 – 138ExtracellularBy similarityAdd BLAST17
Transmembranei139 – 161Helical; Name=Segment S2By similarityAdd BLAST23
Topological domaini162 – 169CytoplasmicBy similarity8
Transmembranei170 – 190Helical; Name=Segment S3By similarityAdd BLAST21
Topological domaini191 – 197ExtracellularBy similarity7
Transmembranei198 – 218Helical; Name=Segment S4By similarityAdd BLAST21
Topological domaini219 – 273CytoplasmicBy similarityAdd BLAST55

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29T → A: Loss of a phosphorylation site. Reduces phosphorylation. 1 Publication1
Mutagenesisi97S → A: Loss of a phosphorylation site. Strongly reduces phosphorylation. 1 Publication1
Mutagenesisi112D → A, F, N or S: Alters channel selectivity. Converts the proton channel to an anion channel. 1 Publication1
Mutagenesisi112D → E: No effect on channel activity and proton selectivity. 1 Publication1
Mutagenesisi112D → V: Abolishes channel activity. 1 Publication1
Mutagenesisi140H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-193. 2 Publications1
Mutagenesisi193H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-140. 2 Publications1
Mutagenesisi205R → A: Faster channel activation and deactivation kinetics. 1 Publication1
Mutagenesisi208R → A: Faster channel activation and deactivation kinetics. 1 Publication1
Mutagenesisi211R → A: Faster channel deactivation kinetics. 1 Publication1

Organism-specific databases

DisGeNETi84329
OpenTargetsiENSG00000122986
PharmGKBiPA144596422

Chemistry databases

GuidetoPHARMACOLOGYi746

Polymorphism and mutation databases

BioMutaiHVCN1
DMDMi74751810

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003421871 – 273Voltage-gated hydrogen channel 1Add BLAST273

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29Phosphothreonine1 Publication1
Modified residuei97Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation may enhance channel gating.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96D96
MaxQBiQ96D96
PaxDbiQ96D96
PeptideAtlasiQ96D96
PRIDEiQ96D96
ProteomicsDBi76259
76260 [Q96D96-2]
76261 [Q96D96-3]

PTM databases

iPTMnetiQ96D96
PhosphoSitePlusiQ96D96

Expressioni

Tissue specificityi

Enriched in immune tissues, such as lymph nodes, B-lymphocytes, monocytes and spleen.1 Publication

Gene expression databases

BgeeiENSG00000122986
CleanExiHS_HVCN1
ExpressionAtlasiQ96D96 baseline and differential
GenevisibleiQ96D96 HS

Organism-specific databases

HPAiHPA039329

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-15704959,EBI-15704959

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi124053, 9 interactors
DIPiDIP-46112N
STRINGi9606.ENSP00000242607

Structurei

Secondary structure

1273
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi227 – 265Combined sources39

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A2AX-ray2.00A/B/C/D221-273[»]
ProteinModelPortaliQ96D96
SMRiQ96D96
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili223 – 2661 PublicationAdd BLAST44

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi46 – 55Poly-Glu10
Compositional biasi176 – 180Poly-Val5

Domaini

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.1 Publication
The C-terminal coiled coil region mediates homodimerization and cooperative channel gating. It is essential for normal subcellular localization.1 Publication

Sequence similaritiesi

Belongs to the hydrogen channel family.Curated

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKBG Eukaryota
ENOG4111XHU LUCA
GeneTreeiENSGT00530000063670
HOGENOMiHOG000067871
HOVERGENiHBG102207
InParanoidiQ96D96
OMAiRMSKFLK
OrthoDBiEOG091G0L8G
PhylomeDBiQ96D96
TreeFamiTF332056

Family and domain databases

Gene3Di1.20.120.350, 1 hit
InterProiView protein in InterPro
IPR031846 Hvcn1
IPR005821 Ion_trans_dom
IPR031844 VGPC1_C
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR12305:SF47 PTHR12305:SF47, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
PF16799 VGPC1_C, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96D96-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MATWDEKAVT RRAKVAPAER MSKFLRHFTV VGDDYHAWNI NYKKWENEEE
60 70 80 90 100
EEEEEQPPPT PVSGEEGRAA APDVAPAPGP APRAPLDFRG MLRKLFSSHR
110 120 130 140 150
FQVIIICLVV LDALLVLAEL ILDLKIIQPD KNNYAAMVFH YMSITILVFF
160 170 180 190 200
MMEIIFKLFV FRLEFFHHKF EILDAVVVVV SFILDIVLLF QEHQFEALGL
210 220 230 240 250
LILLRLWRVA RIINGIIISV KTRSERQLLR LKQMNVQLAA KIQHLEFSCS
260 270
EKEQEIERLN KLLRQHGLLG EVN
Length:273
Mass (Da):31,683
Last modified:December 1, 2001 - v1
Checksum:i0F93B428AECBBC4F
GO
Isoform 2 (identifier: Q96D96-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-102: Missing.

Show »
Length:236
Mass (Da):27,713
Checksum:i1AD13F7D49A62C4D
GO
Isoform 3 (identifier: Q96D96-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     253-273: EQEIERLNKLLRQHGLLGEVN → PLD

Note: No experimental confirmation available.
Show »
Length:255
Mass (Da):29,538
Checksum:i092B095DD219550A
GO
Isoform 4 (identifier: Q96D96-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.

Note: No experimental confirmation available.
Show »
Length:253
Mass (Da):29,415
Checksum:iF1349C26BCC164F1
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti165F → Y in BAG57024 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0450521 – 20Missing in isoform 4. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_03439566 – 102Missing in isoform 2. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_034396253 – 273EQEIE…LGEVN → PLD in isoform 3. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS31900.1 [Q96D96-1]
CCDS58278.1 [Q96D96-4]
RefSeqiNP_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_005253948.2 [Q96D96-1]
XP_011537147.1, XM_011538845.1 [Q96D96-1]
XP_011537148.1, XM_011538846.2 [Q96D96-1]
XP_011537149.1, XM_011538847.1 [Q96D96-1]
XP_016875516.1, XM_017020027.1 [Q96D96-1]
UniGeneiHs.211511
Hs.334637

Genome annotation databases

EnsembliENST00000242607; ENSP00000242607; ENSG00000122986 [Q96D96-1]
ENST00000356742; ENSP00000349181; ENSG00000122986 [Q96D96-1]
ENST00000439744; ENSP00000412052; ENSG00000122986 [Q96D96-4]
ENST00000548312; ENSP00000449601; ENSG00000122986 [Q96D96-3]
ENST00000620084; ENSP00000479812; ENSG00000122986 [Q96D96-1]
GeneIDi84329
KEGGihsa:84329
UCSCiuc001trq.1 human [Q96D96-1]

Keywords - Coding sequence diversityi

Alternative splicing

Entry informationi

Entry nameiHVCN1_HUMAN
AccessioniPrimary (citable) accession number: Q96D96
Secondary accession number(s): A8MQ37
, B4DEB3, F8WCH5, Q6UW11, Q96IS5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: December 1, 2001
Last modified: June 20, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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