Q96D96 (HVCN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Protein existence	Evidence 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
Enzyme regulation	Sensitive to zinc ions and is inhibited by them. Ref.6
Subunit structure	Homodimer. Ref.7
Subcellular location	Membrane; Multi-pass membrane protein. Note: Associates mainly with intracellular compartment membranes. Ref.6 Ref.7
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. The C-terminal coiled coil region mediates homodimerization and is essential for localization.
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.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Transmembrane Transmembrane helix
Molecular function	Ion channel Voltage-gated channel
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to pH Inferred from sequence or structural similarity PubMed 16556803. Source: HGNC response to zinc ion Inferred from direct assay Ref.6. Source: HGNC
Cellular_component	integral to membrane Inferred from direct assay Ref.6. Source: HGNC
Molecular_function	voltage-gated proton channel activity Inferred from direct assay Ref.6. Source: HGNC
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 273

273

Voltage-gated hydrogen channel 1

PRO_0000342187

Regions

Topological domain

1 – 100

100

Cytoplasmic Potential

Transmembrane

101 – 121

21

Helical; Name=Segment S1; By similarity

Topological domain

122 – 135

14

Extracellular Potential

Transmembrane

136 – 156

21

Helical; Name=Segment S2; By similarity

Topological domain

157 – 169

13

Cytoplasmic Potential

Transmembrane

170 – 190

21

Helical; Name=Segment S3; By similarity

Topological domain

191 – 197

7

Extracellular Potential

Transmembrane

198 – 218

21

Helical; Name=Segment S4; By similarity

Topological domain

219 – 273

55

Cytoplasmic Potential

Coiled coil

223 – 266

44

Compositional bias

46 – 55

10

Poly-Glu

Compositional bias

176 – 180

5

Poly-Val

Natural variations

Alternative sequence

1 – 20

20

Missing in isoform 4.

VSP_045052

Alternative sequence

66 – 102

37

Missing in isoform 2.

VSP_034395

Alternative sequence

253 – 273

21

EQEIE…LGEVN → PLD in isoform 3.

VSP_034396

Experimental info

Mutagenesis

140

1

H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-193. Ref.6

Mutagenesis

193

1

H → A: Exhibits selectivity to protons but sensitivity to zinc ions is abolished; when associated with A-140. Ref.6

Mutagenesis

205

1

R → A: Faster channel activation and deactivation kinetics. Ref.6

Mutagenesis

208

1

R → A: Faster channel activation and deactivation kinetics. Ref.6

Mutagenesis

211

1

R → A: Faster channel deactivation kinetics. Ref.6

Sequence conflict

165

1

F → Y in BAG57024. Ref.2

Secondary structure

1

.

.

.

273

Helix Strand Turn

Details...

Helix

227 – 265

39

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 0F93B428AECBBC4F	FASTA	273	31,683
	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
	Isoform 2 [UniParc]. Checksum: 1AD13F7D49A62C4D	FASTA	236	27,713
	10 20 30 40 50 60 MATWDEKAVT RRAKVAPAER MSKFLRHFTV VGDDYHAWNI NYKKWENEEE EEEEEQPPPT 70 80 90 100 110 120 PVSGEVIIIC LVVLDALLVL AELILDLKII QPDKNNYAAM VFHYMSITIL VFFMMEIIFK 130 140 150 160 170 180 LFVFRLEFFH HKFEILDAVV VVVSFILDIV LLFQEHQFEA LGLLILLRLW RVARIINGII 190 200 210 220 230 ISVKTRSERQ LLRLKQMNVQ LAAKIQHLEF SCSEKEQEIE RLNKLLRQHG LLGEVN
	Isoform 3 [UniParc]. Checksum: 092B095DD219550A	FASTA	255	29,538
	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 KIQHLEFSCS EKPLD
	Isoform 4 [UniParc]. Checksum: F1349C26BCC164F1	FASTA	253	29,415
	10 20 30 40 50 60 MSKFLRHFTV VGDDYHAWNI NYKKWENEEE EEEEEQPPPT PVSGEEGRAA APDVAPAPGP 70 80 90 100 110 120 APRAPLDFRG MLRKLFSSHR FQVIIICLVV LDALLVLAEL ILDLKIIQPD KNNYAAMVFH 130 140 150 160 170 180 YMSITILVFF MMEIIFKLFV FRLEFFHHKF EILDAVVVVV SFILDIVLLF QEHQFEALGL 190 200 210 220 230 240 LILLRLWRVA RIINGIIISV KTRSERQLLR LKQMNVQLAA KIQHLEFSCS EKEQEIERLN 250 KLLRQHGLLG EVN

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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]	"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.
+	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.

IPI

IPI00153005.
IPI00478137.
IPI00872288.
IPI01013490.

RefSeq

NP_001035196.1. NM_001040107.1.
NP_001243342.1. NM_001256413.1.
NP_115745.2. NM_032369.3.

UniGene

Hs.211511.
Hs.334637.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A2A	X-ray	2.00	A/B/C/D	221-273	[»]

ProteinModelPortal

Q96D96.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46112N.

MINT

MINT-4724965.

STRING

9606.ENSP00000349181.

Protein family/group databases

TCDB

1.A.51.1.2. voltage-gated proton channel (VPC) family.

PTM databases

PhosphoSite

Q96D96.

Polymorphism databases

DMDM

74751810.

Proteomic databases

PaxDb

Q96D96.

PRIDE

Q96D96.

Protocols and materials databases

DNASU

84329.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000242607; ENSP00000242607; ENSG00000122986.
ENST00000356742; ENSP00000349181; ENSG00000122986.
ENST00000439744; ENSP00000412052; ENSG00000122986.
ENST00000548312; ENSP00000449601; ENSG00000122986.

GeneID

84329.

KEGG

hsa:84329.

UCSC

uc001trq.1. human.
uc001trs.1. human.

Organism-specific databases

CTD

84329.

GeneCards

GC12M111086.

H-InvDB

HIX0011039.

HGNC

HGNC:28240. HVCN1.

HPA

HPA039329.

MIM

611227. gene.

neXtProt

NX_Q96D96.

PharmGKB

PA144596422.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46709.

HOGENOM

HOG000067871.

HOVERGEN

HBG102207.

InParanoid

Q96D96.

OMA

FFMMEIF.

OrthoDB

EOG4GF3G9.

PhylomeDB

Q96D96.

Gene expression databases

ArrayExpress

Q96D96.

Bgee

Q96D96.

CleanEx

HS_HVCN1.

Genevestigator

Q96D96.

Family and domain databases

Gene3D

1.20.120.350. 1 hit.

InterPro

IPR005821. Ion_trans_dom.
IPR027359. K_channel_four-helix_dom.
[Graphical view]

Pfam

PF00520. Ion_trans. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HVCN1. human.

GenomeRNAi

84329.

NextBio

74079.

SOURCE

Search...

Entry information

Entry name

HVCN1_HUMAN

Accession

Primary (citable) accession number: Q96D96
Secondary accession number(s): A8MQ37 , B4DEB3, F8WCH5, Q6UW11, Q96IS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	December 1, 2001
Last modified:	May 29, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.