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Protein

Neuronal acetylcholine receptor subunit alpha-2

Gene

CHRNA2

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

Functioni

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Caution

With the use of epibatidine as high affinity ligand, an alpha-2 homopentamer has been purified and crystallized. Its physiological relevance has not been proven.1 Publication

GO - Molecular functioni

  • acetylcholine binding Source: Ensembl
  • acetylcholine-gated cation-selective channel activity Source: UniProtKB
  • acetylcholine receptor activity Source: UniProtKB
  • ligand-gated ion channel activity Source: Reactome

GO - Biological processi

  • ion transport Source: UniProtKB
  • neuromuscular synaptic transmission Source: GO_Central
  • protein heterooligomerization Source: Ensembl
  • response to nicotine Source: GO_Central
  • signal transduction Source: UniProtKB
  • synaptic transmission, cholinergic Source: GO_Central

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-629594 Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597 Highly calcium permeable nicotinic acetylcholine receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal acetylcholine receptor subunit alpha-2
Gene namesi
Name:CHRNA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000120903.11
HGNCiHGNC:1956 CHRNA2
MIMi118502 gene
neXtProtiNX_Q15822

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 domaini27 – 264ExtracellularAdd BLAST238
Transmembranei265 – 289HelicalSequence analysisAdd BLAST25
Transmembranei297 – 315HelicalSequence analysisAdd BLAST19
Transmembranei331 – 352HelicalSequence analysisAdd BLAST22
Topological domaini353 – 502CytoplasmicAdd BLAST150
Transmembranei503 – 521HelicalSequence analysisAdd BLAST19

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Epilepsy, nocturnal frontal lobe, 4 (ENFL4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking.
See also OMIM:610353
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027641279I → N in ENFL4; markedly increases receptor sensitivity to acetylcholine. 1 PublicationCorresponds to variant dbSNP:rs104894063EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi115W → A: Changes ligand activation kinetics in a alpha-2(+):alpha-2(-) subunit interface (in LS nAChR subtype). 1 Publication1
Mutagenesisi225Y → F: Decreases ligand activation in LS nAChR subtype; no effect in HS nAChR subtype. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi1135
GeneReviewsiCHRNA2
MalaCardsiCHRNA2
MIMi610353 phenotype
OpenTargetsiENSG00000120903
Orphaneti98784 Autosomal dominant nocturnal frontal lobe epilepsy
PharmGKBiPA26489

Chemistry databases

ChEMBLiCHEMBL2109230
DrugBankiDB00732 Atracurium besylate
DB00810 Biperiden
DB00411 Carbachol
DB00565 Cisatracurium besylate
DB01245 Decamethonium
DB00514 Dextromethorphan
DB01135 Doxacurium chloride
DB00898 Ethanol
DB00674 Galantamine
DB00483 Gallamine Triethiodide
DB00657 Mecamylamine
DB01336 Metocurine
DB00416 Metocurine Iodide
DB01226 Mivacurium
DB00184 Nicotine
DB01337 Pancuronium
DB01338 Pipecuronium
DB00721 Procaine
DB00728 Rocuronium
DB05740 RPI-78M
DB01199 Tubocurarine
DB01339 Vecuronium
GuidetoPHARMACOLOGYi463

Polymorphism and mutation databases

BioMutaiCHRNA2
DMDMi308153405

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000000034027 – 529Neuronal acetylcholine receptor subunit alpha-2Add BLAST503

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi79N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi183 ↔ 197By similarity
Glycosylationi235N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi247 ↔ 248Associated with receptor activationBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ15822
PaxDbiQ15822
PeptideAtlasiQ15822
PRIDEiQ15822
ProteomicsDBi60776

PTM databases

iPTMnetiQ15822
PhosphoSitePlusiQ15822

Expressioni

Gene expression databases

BgeeiENSG00000120903
CleanExiHS_CHRNA2
ExpressionAtlasiQ15822 baseline and differential
GenevisibleiQ15822 HS

Interactioni

Subunit structurei

Neuronal AChR seems to be composed of two different types of subunits: alpha and non-alpha (beta). Alpha-2 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors. The alpha-2:beta-2 nAChR complex is proposed to be a heteropentamer with two subtypes: LS (low agonist sensitivity) with a (alpha-2)3:(beta-2)2 and HS (high agonist sensitivity) with a (alpha-2)2:(beta-2)3 stoichiometry; the subtypes differ in their subunit binding interfaces which are involved in ligand binding.1 Publication

Protein-protein interaction databases

ComplexPortaliCPX-2170 Neuronal nicotinic acetylcholine receptor complex, alpha2-beta2
CPX-2190 Neuronal nicotinic acetylcholine receptor complex, alpha2-beta4
CORUMiQ15822
STRINGi9606.ENSP00000385026

Chemistry databases

BindingDBiQ15822

Structurei

Secondary structure

1529
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi61 – 69Combined sources9
Beta strandi74 – 76Combined sources3
Beta strandi78 – 82Combined sources5
Beta strandi84 – 99Combined sources16
Turni100 – 103Combined sources4
Beta strandi104 – 116Combined sources13
Helixi118 – 120Combined sources3
Turni124 – 129Combined sources6
Beta strandi131 – 136Combined sources6
Turni137 – 139Combined sources3
Beta strandi145 – 147Combined sources3
Turni148 – 150Combined sources3
Beta strandi162 – 166Combined sources5
Turni167 – 169Combined sources3
Beta strandi170 – 173Combined sources4
Beta strandi176 – 182Combined sources7
Beta strandi190 – 192Combined sources3
Beta strandi198 – 205Combined sources8
Turni208 – 210Combined sources3
Beta strandi211 – 215Combined sources5
Turni217 – 219Combined sources3
Beta strandi237 – 245Combined sources9
Beta strandi248 – 258Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FJVX-ray3.20A/B/C/D/E59-265[»]
ProteinModelPortaliQ15822
SMRiQ15822
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3645 Eukaryota
ENOG410XQGR LUCA
GeneTreeiENSGT00760000118930
HOGENOMiHOG000006756
HOVERGENiHBG003756
InParanoidiQ15822
KOiK04804
OMAiPSYHWLE
OrthoDBiEOG091G0R20
PhylomeDBiQ15822
TreeFamiTF315605

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
IPR002394 Nicotinic_acetylcholine_rcpt
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR00254 NICOTINICR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15822-1) [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
MGPSCPVFLS FTKLSLWWLL LTPAGGEEAK RPPPRAPGDP LSSPSPTALP
60 70 80 90 100
QGGSHTETED RLFKHLFRGY NRWARPVPNT SDVVIVRFGL SIAQLIDVDE
110 120 130 140 150
KNQMMTTNVW LKQEWSDYKL RWNPTDFGNI TSLRVPSEMI WIPDIVLYNN
160 170 180 190 200
ADGEFAVTHM TKAHLFSTGT VHWVPPAIYK SSCSIDVTFF PFDQQNCKMK
210 220 230 240 250
FGSWTYDKAK IDLEQMEQTV DLKDYWESGE WAIVNATGTY NSKKYDCCAE
260 270 280 290 300
IYPDVTYAFV IRRLPLFYTI NLIIPCLLIS CLTVLVFYLP SDCGEKITLC
310 320 330 340 350
ISVLLSLTVF LLLITEIIPS TSLVIPLIGE YLLFTMIFVT LSIVITVFVL
360 370 380 390 400
NVHHRSPSTH TMPHWVRGAL LGCVPRWLLM NRPPPPVELC HPLRLKLSPS
410 420 430 440 450
YHWLESNVDA EEREVVVEEE DRWACAGHVA PSVGTLCSHG HLHSGASGPK
460 470 480 490 500
AEALLQEGEL LLSPHMQKAL EGVHYIADHL RSEDADSSVK EDWKYVAMVI
510 520
DRIFLWLFII VCFLGTIGLF LPPFLAGMI
Length:529
Mass (Da):59,765
Last modified:October 5, 2010 - v2
Checksum:iE47062A1145E8BCC
GO
Isoform 2 (identifier: Q15822-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     82-96: Missing.

Note: No experimental confirmation available.
Show »
Length:514
Mass (Da):58,140
Checksum:i777F58CA00518BC8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02763922T → I. Corresponds to variant dbSNP:rs2472553EnsemblClinVar.1
Natural variantiVAR_027640125T → A3 PublicationsCorresponds to variant dbSNP:rs891398EnsemblClinVar.1
Natural variantiVAR_027641279I → N in ENFL4; markedly increases receptor sensitivity to acetylcholine. 1 PublicationCorresponds to variant dbSNP:rs104894063EnsemblClinVar.1
Natural variantiVAR_076498376R → W Found in patients with benign familial infantile seizures; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1018084204Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05515682 – 96Missing in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62431 mRNA Translation: AAB40109.1
Y16281 mRNA Translation: CAA76154.1
AK296348 mRNA Translation: BAG59031.1
AF311103 Genomic DNA No translation available.
BC153866 mRNA Translation: AAI53867.1
CCDSiCCDS6059.1 [Q15822-1]
CCDS64856.1 [Q15822-2]
RefSeqiNP_000733.2, NM_000742.3 [Q15822-1]
NP_001269384.1, NM_001282455.1 [Q15822-2]
XP_006716345.1, XM_006716282.1 [Q15822-1]
XP_011542690.1, XM_011544388.1 [Q15822-1]
UniGeneiHs.57718

Genome annotation databases

EnsembliENST00000240132; ENSP00000240132; ENSG00000120903 [Q15822-2]
ENST00000407991; ENSP00000385026; ENSG00000120903 [Q15822-1]
GeneIDi1135
KEGGihsa:1135
UCSCiuc010lur.4 human [Q15822-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiACHA2_HUMAN
AccessioniPrimary (citable) accession number: Q15822
Secondary accession number(s): A8KAX3
, B4DK19, J3KMY9, Q9HAQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 5, 2010
Last modified: June 20, 2018
This is version 168 of the entry and version 2 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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