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Protein

Neuronal acetylcholine receptor subunit alpha-9

Gene

CHRNA9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasma membrane (PubMed:11752216, PubMed:25282151). The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane (PubMed:11752216, PubMed:25282151). In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion (PubMed:11021840).Curated3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiREACT_22303. Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal acetylcholine receptor subunit alpha-9
Alternative name(s):
Nicotinic acetylcholine receptor subunit alpha-9
Short name:
NACHR alpha-9
Gene namesi
Name:CHRNA9
Synonyms:NACHRA9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:14079. CHRNA9.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 237212ExtracellularSequence AnalysisAdd
BLAST
Transmembranei238 – 26225HelicalSequence AnalysisAdd
BLAST
Transmembranei269 – 28719HelicalSequence AnalysisAdd
BLAST
Transmembranei302 – 32322HelicalSequence AnalysisAdd
BLAST
Topological domaini324 – 457134CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei458 – 47619HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • acetylcholine-gated channel complex Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • cytosol Source: GOC
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
  • postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26493.

Chemistry

DrugBankiDB00674. Galantamine.
DB00184. Nicotine.

Polymorphism and mutation databases

BioMutaiCHRNA9.
DMDMi308153406.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 479454Neuronal acetylcholine receptor subunit alpha-9PRO_0000000371Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi57 – 571N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi155 ↔ 1691 Publication
Glycosylationi170 – 1701N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi219 ↔ 2201 Publication

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9UGM1.
PaxDbiQ9UGM1.
PRIDEiQ9UGM1.

PTM databases

PhosphoSiteiQ9UGM1.

Expressioni

Tissue specificityi

Expressed in cochlea, keratinocytes, pituitary gland, B-cells and T-cells.3 Publications

Gene expression databases

BgeeiQ9UGM1.
CleanExiHS_CHRNA9.
GenevisibleiQ9UGM1. HS.

Interactioni

Subunit structurei

Can form homo- or hetero-oligomeric channels in conjunction with CHRNA10 (PubMed:11752216). The native outer hair cell receptor may be composed of CHRNA9-CHRNA10 hetero-oligomers.1 Publication

Protein-protein interaction databases

BioGridi120731. 63 interactions.
DIPiDIP-61053N.
STRINGi9606.ENSP00000312663.

Structurei

Secondary structure

1
479
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi30 – 3910Combined sources
Beta strandi49 – 513Combined sources
Beta strandi56 – 7116Combined sources
Turni72 – 754Combined sources
Beta strandi76 – 9318Combined sources
Helixi96 – 983Combined sources
Turni99 – 1013Combined sources
Beta strandi104 – 1085Combined sources
Helixi109 – 1113Combined sources
Beta strandi117 – 1193Combined sources
Beta strandi134 – 1385Combined sources
Beta strandi140 – 15415Combined sources
Beta strandi156 – 1583Combined sources
Beta strandi164 – 17714Combined sources
Turni180 – 1823Combined sources
Beta strandi183 – 1919Combined sources
Beta strandi201 – 2077Combined sources
Beta strandi209 – 2179Combined sources
Turni218 – 2203Combined sources
Beta strandi224 – 23512Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4D01X-ray1.80A26-237[»]
4UXUX-ray1.71A/B26-237[»]
4UY2X-ray2.70A/B26-237[»]
ProteinModelPortaliQ9UGM1.
SMRiQ9UGM1. Positions 28-349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG306809.
GeneTreeiENSGT00790000122957.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiQ9UGM1.
KOiK04810.
OMAiQWARVVI.
OrthoDBiEOG72JWGV.
PhylomeDBiQ9UGM1.
TreeFamiTF315605.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
IPR002394. Nicotinic_acetylcholine_rcpt.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UGM1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNWSHSCISF CWIYFAASRL RAAETADGKY AQKLFNDLFE DYSNALRPVE
60 70 80 90 100
DTDKVLNVTL QITLSQIKDM DERNQILTAY LWIRQIWHDA YLTWDRDQYD
110 120 130 140 150
GLDSIRIPSD LVWRPDIVLY NKADDESSEP VNTNVVLRYD GLITWDAPAI
160 170 180 190 200
TKSSCVVDVT YFPFDNQQCN LTFGSWTYNG NQVDIFNALD SGDLSDFIED
210 220 230 240 250
VEWEVHGMPA VKNVISYGCC SEPYPDVTFT LLLKRRSSFY IVNLLIPCVL
260 270 280 290 300
ISFLAPLSFY LPAASGEKVS LGVTILLAMT VFQLMVAEIM PASENVPLIG
310 320 330 340 350
KYYIATMALI TASTALTIMV MNIHFCGAEA RPVPHWARVV ILKYMSRVLF
360 370 380 390 400
VYDVGESCLS PHHSRERDHL TKVYSKLPES NLKAARNKDL SRKKDMNKRL
410 420 430 440 450
KNDLGCQGKN PQEAESYCAQ YKVLTRNIEY IAKCLKDHKA TNSKGSEWKK
460 470
VAKVIDRFFM WIFFIMVFVM TILIIARAD
Length:479
Mass (Da):54,807
Last modified:October 5, 2010 - v2
Checksum:iAA6B46B559D6111D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961R → Q.
Corresponds to variant rs10024518 [ dbSNP | Ensembl ].
VAR_031151
Natural varianti315 – 3151A → V.
Corresponds to variant rs55633891 [ dbSNP | Ensembl ].
VAR_060996
Natural varianti442 – 4421N → S.3 Publications
Corresponds to variant rs10009228 [ dbSNP | Ensembl ].
VAR_025425

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ243342 mRNA. Translation: CAB65091.1.
AY123244 Genomic DNA. Translation: AAM74523.1.
AC118275 Genomic DNA. Translation: AAY40986.1.
BC113549 mRNA. Translation: AAI13550.1.
BC113575 mRNA. Translation: AAI13576.1.
AF227732 mRNA. Translation: AAF61920.1.
CCDSiCCDS3459.1.
RefSeqiNP_060051.2. NM_017581.3.
UniGeneiHs.272278.

Genome annotation databases

EnsembliENST00000310169; ENSP00000312663; ENSG00000174343.
GeneIDi55584.
KEGGihsa:55584.
UCSCiuc003gva.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ243342 mRNA. Translation: CAB65091.1.
AY123244 Genomic DNA. Translation: AAM74523.1.
AC118275 Genomic DNA. Translation: AAY40986.1.
BC113549 mRNA. Translation: AAI13550.1.
BC113575 mRNA. Translation: AAI13576.1.
AF227732 mRNA. Translation: AAF61920.1.
CCDSiCCDS3459.1.
RefSeqiNP_060051.2. NM_017581.3.
UniGeneiHs.272278.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4D01X-ray1.80A26-237[»]
4UXUX-ray1.71A/B26-237[»]
4UY2X-ray2.70A/B26-237[»]
ProteinModelPortaliQ9UGM1.
SMRiQ9UGM1. Positions 28-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120731. 63 interactions.
DIPiDIP-61053N.
STRINGi9606.ENSP00000312663.

Chemistry

BindingDBiQ9UGM1.
ChEMBLiCHEMBL2184.
DrugBankiDB00674. Galantamine.
DB00184. Nicotine.
GuidetoPHARMACOLOGYi469.

PTM databases

PhosphoSiteiQ9UGM1.

Polymorphism and mutation databases

BioMutaiCHRNA9.
DMDMi308153406.

Proteomic databases

MaxQBiQ9UGM1.
PaxDbiQ9UGM1.
PRIDEiQ9UGM1.

Protocols and materials databases

DNASUi55584.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310169; ENSP00000312663; ENSG00000174343.
GeneIDi55584.
KEGGihsa:55584.
UCSCiuc003gva.2. human.

Organism-specific databases

CTDi55584.
GeneCardsiGC04P040337.
H-InvDBHIX0031380.
HGNCiHGNC:14079. CHRNA9.
MIMi605116. gene.
neXtProtiNX_Q9UGM1.
PharmGKBiPA26493.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG306809.
GeneTreeiENSGT00790000122957.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiQ9UGM1.
KOiK04810.
OMAiQWARVVI.
OrthoDBiEOG72JWGV.
PhylomeDBiQ9UGM1.
TreeFamiTF315605.

Enzyme and pathway databases

ReactomeiREACT_22303. Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.

Miscellaneous databases

ChiTaRSiCHRNA9. human.
GeneWikiiCHRNA9.
GenomeRNAii55584.
NextBioi60096.
PROiQ9UGM1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UGM1.
CleanExiHS_CHRNA9.
GenevisibleiQ9UGM1. HS.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
IPR002394. Nicotinic_acetylcholine_rcpt.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit."
    Sgard F., Charpantier E., Bertrand S., Walker N., Caput D., Graham D., Bertrand D., Besnard F.
    Mol. Pharmacol. 61:150-159(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CHRNA10, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT SER-442.
    Tissue: Embryo.
  2. "Chromosome location and characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) gene."
    Lustig L.R., Peng H.
    Cytogenet. Genome Res. 98:154-159(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-442.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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], VARIANT SER-442.
  5. "Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity."
    Nguyen V.T., Ndoye A., Grando S.A.
    Am. J. Pathol. 157:1377-1391(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-476, FUNCTION, TISSUE SPECIFICITY.
  6. "Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes."
    Peng H., Ferris R.L., Matthews T., Hiel H., Lopez-Albaitero A., Lustig L.R.
    Life Sci. 76:263-280(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain."
    Zouridakis M., Giastas P., Zarkadas E., Chroni-Tzartou D., Bregestovski P., Tzartos S.J.
    Nat. Struct. Mol. Biol. 21:976-980(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 26-237, FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, GLYCOSYLATION.

Entry informationi

Entry nameiACHA9_HUMAN
AccessioniPrimary (citable) accession number: Q9UGM1
Secondary accession number(s): Q14CY7, Q4W5A2, Q9NYV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 5, 2010
Last modified: July 22, 2015
This is version 136 of the entry and version 2 of the sequence. [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

Miscellaneous

The hetero-oligomeric receptor composed of CHRNA9 and CHRNA10 has an atypical pharmacological profile, binding several non-nicotinic ligands including strychnine (a glycine receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.