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1.A.51.1.2
The voltage-gated proton channel, Hv1, Hv1 or HVCN1 (273 aas) (Ramsey et al., 2006). Thr29 is a phosphorylation site that activates the HVCN1 channel in leukocytes (Musset et al., 2010). The condctivity pore has been delineated and depends of a carboxyl group (Asp or Glu) in the channel (Morgan et al. 2013). The four transmembrane helices sense voltage and the pH gradient, and conduct protons exclusively. Selectivity is achieved by the unique ability of H3O+ to protonate an Asp-Arg salt bridge. Pathognomonic sensitivity of gating to the pH gradient ensures HV1 channel opening only when acid extrusion will result, which is crucial to its biological functions (DeCoursey 2015). An exception occurs in dinoflagellates (see 1.A.51.1.4) in which H+ influx through HV1 triggers a bioluminescent flash. The gating mechanism of Hv1, cooperativity within dimers and the sensitivity to metal ions have been reviewed (Okamura et al. 2015). How this channel is activated by cytoplasmic [H+] and depolarization of the membrane potential has been proposed by Castillo et al. 2015. The extracellular ends of the first transmembrane segments form the intersubunit interface that mediates coupling between binding sites, while the coiled-coil domain does not directly participate in the process (Hong et al. 2015). Deep water penetration through hHv1 has been observed, suggesting a highly focused electric field, comprising two helical turns along the fourth TMS. This region likely contains the H+ selectivity filter and the conduction pore. A 3D model offers an explicit mechanism for voltage activation based on a one-click sliding helix conformational rearrangement (Li et al. 2015).  Trp-207 enables four characteristic properties: slow channel opening, highly temperature-dependent gating kinetics, proton selectivity, and ΔpH-dependent gating (Cherny et al. 2015).  The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively (Okuda et al. 2016).  Segment S3 plays a role in activating gating (Sakata et al. 2016).  Two sites have been identified: one is the binding pocket of 2GBI (accessible to ligands from the intracellular side); the other is located at the exit site of the proton permeation pathway (Gianti et al. 2016).

Accession Number:Q96D96
Protein Name:Hv1 aka HVCN1
Length:273
Molecular Weight:31683.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate H+

Cross database links:

Genevestigator: Q96D96
eggNOG: prNOG15301
HEGENOM: HBG714522
DIP: DIP-46112N
RefSeq: NP_001035196.1    NP_115745.2   
Entrez Gene ID: 84329   
Pfam: PF00520   
OMIM: 611227  gene
KEGG: hsa:84329   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0030171 F:voltage-gated proton channel activity
GO:0015992 P:proton transport
GO:0009268 P:response to pH
GO:0010043 P:response to zinc ion
GO:0055085 P:transmembrane transport

References (4)

[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.et.al.   12975309
[2] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “A voltage-gated proton-selective channel lacking the pore domain.”  Ramsey I.S.et.al.   16554753
Structure:
3A2A     

External Searches:

  • Search: DB with
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  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MATWDEKAVT RRAKVAPAER MSKFLRHFTV VGDDYHAWNI NYKKWENEEE EEEEEQPPPT 
61:	PVSGEEGRAA APDVAPAPGP APRAPLDFRG MLRKLFSSHR FQVIIICLVV LDALLVLAEL 
121:	ILDLKIIQPD KNNYAAMVFH YMSITILVFF MMEIIFKLFV FRLEFFHHKF EILDAVVVVV 
181:	SFILDIVLLF QEHQFEALGL LILLRLWRVA RIINGIIISV KTRSERQLLR LKQMNVQLAA 
241:	KIQHLEFSCS EKEQEIERLN KLLRQHGLLG EVN