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Protein

Acetylcholine receptor subunit epsilon

Gene

CHRNE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

GO - Molecular functioni

  • acetylcholine-gated cation-selective channel activity Source: ProtInc
  • acetylcholine receptor activity Source: ProtInc
  • cation transmembrane transporter activity Source: ProtInc
  • ligand-gated ion channel activity Source: Reactome

GO - Biological processi

  • muscle contraction Source: ProtInc
  • neuromuscular synaptic transmission Source: GO_Central
  • response to nicotine Source: GO_Central
  • signal transduction Source: ProtInc
  • synaptic transmission, cholinergic Source: ProtInc
  • transport Source: ProtInc

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-629587. Highly sodium permeable acetylcholine nicotinic receptors.

Protein family/group databases

TCDBi1.A.9.1.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Acetylcholine receptor subunit epsilon
Gene namesi
Name:CHRNE
Synonyms:ACHRE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108556.7.
HGNCiHGNC:1966. CHRNE.

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 domaini21 – 239ExtracellularSequence analysisAdd BLAST219
Transmembranei240 – 264HelicalSequence analysisAdd BLAST25
Topological domaini265 – 272CytoplasmicSequence analysis8
Transmembranei273 – 291HelicalSequence analysisAdd BLAST19
Topological domaini292 – 306ExtracellularSequence analysisAdd BLAST15
Transmembranei307 – 328HelicalSequence analysisAdd BLAST22
Topological domaini329 – 456CytoplasmicSequence analysisAdd BLAST128
Transmembranei457 – 480HelicalSequence analysisAdd BLAST24
Topological domaini481 – 493ExtracellularSequence analysisAdd BLAST13

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.
Myasthenic syndrome, congenital, 4A, slow-channel (CMS4A)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
See also OMIM:605809
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01956798L → P in CMS4A; rare example of recessive inheritance. 1 PublicationCorresponds to variant dbSNP:rs28929768Ensembl.1
Natural variantiVAR_019568241L → F in CMS4A; mild form with variable penetrance. 1 PublicationCorresponds to variant dbSNP:rs28999110Ensembl.1
Natural variantiVAR_000292284T → P in CMS4A; markedly prolonged channel openings in presence of agonist; as well as opening in the absence of agonist. 1 PublicationCorresponds to variant dbSNP:rs121909510Ensembl.1
Natural variantiVAR_077364285V → A in CMS4A; slow-channel mutation; increases gating equilibrium constant by 25-fold, owing to increased opening rate and decreased closing rate; no effect on the choline dissociation rate constant. 1 Publication1
Natural variantiVAR_000293289L → F in CMS4A; slows rate of AChR channel closure and increases apparent affinity for ACh; causes pathologic channel openings even in the absence of ACh resulting in a leaky channel. 2 PublicationsCorresponds to variant dbSNP:rs121909511Ensembl.1
Myasthenic syndrome, congenital, 4B, fast-channel (CMS4B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
See also OMIM:616324
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02121313G → R in CMS4B; impaired association with alpha CHRNA1 subunit of AChR. 1 PublicationCorresponds to variant dbSNP:rs372635387Ensembl.1
Natural variantiVAR_07162975W → R in CMS4B; strongly reduces agonist affinity and gating efficiency. 1 PublicationCorresponds to variant dbSNP:rs193919341Ensembl.1
Natural variantiVAR_000289141P → L in CMS4B; marked decrease in rate of AChR channel opening; reduction in frequency of open channel state and resistance to desensitization by ACh. 1 PublicationCorresponds to variant dbSNP:rs121909512Ensembl.1
Natural variantiVAR_021214163S → L in CMS4B; fails to assemble with alpha CHRNA1 subunit of AChR. 1 PublicationCorresponds to variant dbSNP:rs121909516Ensembl.1
Natural variantiVAR_021215431A → P in CMS4B; causes an increase in distributions of rates for channel opening and closing increasing the range of activation kinetics. 1 PublicationCorresponds to variant dbSNP:rs121909517Ensembl.1
Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency (CMS4C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.
See also OMIM:608931
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000290167R → L in CMS4C; significantly reduced AChR expression. 1 PublicationCorresponds to variant dbSNP:rs121909514Ensembl.1
Natural variantiVAR_000291265P → L in CMS4C; prolongs burst open duration 2-fold by slowing the rate of channel closing. 1 PublicationCorresponds to variant dbSNP:rs759226183Ensembl.1
Natural variantiVAR_000294331R → W in CMS4C; shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation; has a mild fast-channel kinetic effect on the AChR by shortening the long burst and increasing the decay of the endplate current. 1 PublicationCorresponds to variant dbSNP:rs121909515Ensembl.1

Keywords - Diseasei

Congenital myasthenic syndrome, Disease mutation

Organism-specific databases

DisGeNETi1145.
GeneReviewsiCHRNE.
MalaCardsiCHRNE.
MIMi254200. phenotype.
605809. phenotype.
608931. phenotype.
616324. phenotype.
OpenTargetsiENSG00000108556.
Orphaneti98913. Postsynaptic congenital myasthenic syndromes.
PharmGKBiPA26498.

Chemistry databases

ChEMBLiCHEMBL2484.
DrugBankiDB00674. Galantamine.

Polymorphism and mutation databases

BioMutaiCHRNE.
DMDMi1168301.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Add BLAST20
ChainiPRO_000000032921 – 493Acetylcholine receptor subunit epsilonAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi86N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi148 ↔ 162By similarity
Glycosylationi161N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ04844.
PaxDbiQ04844.
PeptideAtlasiQ04844.
PRIDEiQ04844.

PTM databases

iPTMnetiQ04844.
PhosphoSitePlusiQ04844.

Expressioni

Gene expression databases

BgeeiENSG00000108556.
CleanExiHS_CHRNE.
GenevisibleiQ04844. HS.

Interactioni

Subunit structurei

Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).1 Publication

Protein-protein interaction databases

BioGridi107567. 2 interactors.
STRINGi9606.ENSP00000293780.

Chemistry databases

BindingDBiQ04844.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DF9model-A240-332[»]
ProteinModelPortaliQ04844.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3645. Eukaryota.
ENOG410XQGR. LUCA.
GeneTreeiENSGT00760000118930.
HOGENOMiHOG000006757.
HOVERGENiHBG003756.
InParanoidiQ04844.
KOiK04817.
OMAiESTRDQE.
OrthoDBiEOG091G0R20.
PhylomeDBiQ04844.
TreeFamiTF315605.

Family and domain databases

Gene3Di1.20.58.390. 1 hit.
2.70.170.10. 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.
PROSITEiView protein in PROSITE
PS00236. NEUROTR_ION_CHANNEL. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q04844-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARAPLGVLL LLGLLGRGVG KNEELRLYHH LFNNYDPGSR PVREPEDTVT
60 70 80 90 100
ISLKVTLTNL ISLNEKEETL TTSVWIGIDW QDYRLNYSKD DFGGIETLRV
110 120 130 140 150
PSELVWLPEI VLENNIDGQF GVAYDANVLV YEGGSVTWLP PAIYRSVCAV
160 170 180 190 200
EVTYFPFDWQ NCSLIFRSQT YNAEEVEFTF AVDNDGKTIN KIDIDTEAYT
210 220 230 240 250
ENGEWAIDFC PGVIRRHHGG ATDGPGETDV IYSLIIRRKP LFYVINIIVP
260 270 280 290 300
CVLISGLVLL AYFLPAQAGG QKCTVSINVL LAQTVFLFLI AQKIPETSLS
310 320 330 340 350
VPLLGRFLIF VMVVATLIVM NCVIVLNVSQ RTPTTHAMSP RLRHVLLELL
360 370 380 390 400
PRLLGSPPPP EAPRAASPPR RASSVGLLLR AEELILKKPR SELVFEGQRH
410 420 430 440 450
RQGTWTAAFC QSLGAAAPEV RCCVDAVNFV AESTRDQEAT GEEVSDWVRM
460 470 480 490
GNALDNICFW AALVLFSVGS SLIFLGAYFN RVPDLPYAPC IQP
Length:493
Mass (Da):54,697
Last modified:November 1, 1995 - v2
Checksum:iA34AF273AF8B31FE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02121313G → R in CMS4B; impaired association with alpha CHRNA1 subunit of AChR. 1 PublicationCorresponds to variant dbSNP:rs372635387Ensembl.1
Natural variantiVAR_04817018G → V. Corresponds to variant dbSNP:rs4790235Ensembl.1
Natural variantiVAR_07162975W → R in CMS4B; strongly reduces agonist affinity and gating efficiency. 1 PublicationCorresponds to variant dbSNP:rs193919341Ensembl.1
Natural variantiVAR_01956798L → P in CMS4A; rare example of recessive inheritance. 1 PublicationCorresponds to variant dbSNP:rs28929768Ensembl.1
Natural variantiVAR_000289141P → L in CMS4B; marked decrease in rate of AChR channel opening; reduction in frequency of open channel state and resistance to desensitization by ACh. 1 PublicationCorresponds to variant dbSNP:rs121909512Ensembl.1
Natural variantiVAR_021214163S → L in CMS4B; fails to assemble with alpha CHRNA1 subunit of AChR. 1 PublicationCorresponds to variant dbSNP:rs121909516Ensembl.1
Natural variantiVAR_000290167R → L in CMS4C; significantly reduced AChR expression. 1 PublicationCorresponds to variant dbSNP:rs121909514Ensembl.1
Natural variantiVAR_019568241L → F in CMS4A; mild form with variable penetrance. 1 PublicationCorresponds to variant dbSNP:rs28999110Ensembl.1
Natural variantiVAR_000291265P → L in CMS4C; prolongs burst open duration 2-fold by slowing the rate of channel closing. 1 PublicationCorresponds to variant dbSNP:rs759226183Ensembl.1
Natural variantiVAR_000292284T → P in CMS4A; markedly prolonged channel openings in presence of agonist; as well as opening in the absence of agonist. 1 PublicationCorresponds to variant dbSNP:rs121909510Ensembl.1
Natural variantiVAR_077364285V → A in CMS4A; slow-channel mutation; increases gating equilibrium constant by 25-fold, owing to increased opening rate and decreased closing rate; no effect on the choline dissociation rate constant. 1 Publication1
Natural variantiVAR_000293289L → F in CMS4A; slows rate of AChR channel closure and increases apparent affinity for ACh; causes pathologic channel openings even in the absence of ACh resulting in a leaky channel. 2 PublicationsCorresponds to variant dbSNP:rs121909511Ensembl.1
Natural variantiVAR_000294331R → W in CMS4C; shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation; has a mild fast-channel kinetic effect on the AChR by shortening the long burst and increasing the decay of the endplate current. 1 PublicationCorresponds to variant dbSNP:rs121909515Ensembl.1
Natural variantiVAR_021215431A → P in CMS4B; causes an increase in distributions of rates for channel opening and closing increasing the range of activation kinetics. 1 PublicationCorresponds to variant dbSNP:rs121909517Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66403 mRNA. Translation: CAA47030.1.
AF105999 Genomic DNA. Translation: AAD24503.1.
CH471108 Genomic DNA. Translation: EAW90395.1.
CH471108 Genomic DNA. Translation: EAW90396.1.
CCDSiCCDS11058.1.
PIRiS34775.
RefSeqiNP_000071.1. NM_000080.3.
UniGeneiHs.654535.

Genome annotation databases

EnsembliENST00000293780; ENSP00000293780; ENSG00000108556.
GeneIDi1145.
KEGGihsa:1145.
UCSCiuc002fzk.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiACHE_HUMAN
AccessioniPrimary (citable) accession number: Q04844
Secondary accession number(s): D3DTK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 1, 1995
Last modified: October 25, 2017
This is version 169 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

Documents

  1. Human chromosome 17
    Human chromosome 17: 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