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Q04844 (ACHE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acetylcholine receptor subunit epsilon
Gene names
Name:CHRNE
Synonyms:ACHRE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains.

Subcellular location

Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.

Involvement in disease

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, slow-channel (SCCMS) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by 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. Congenital myasthenic syndrome slow-channel type is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5 Ref.6 Ref.10

Myasthenic syndrome, congenital, fast-channel (FCCMS) [MIM:608930]: A congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. Due in most cases to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9

Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]: A post-synaptic congenital myasthenic syndrome. Congenital myasthenic syndromes (CMS) are inherited disorders of neuromuscular transmission that stem from mutations in presynaptic, synaptic, or postsynaptic proteins.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Epsilon/CHRNE sub-subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityPolymorphism
   DiseaseCongenital myasthenic syndrome
Disease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcation transport

Traceable author statement Ref.5Ref.6. Source: GOC

muscle contraction

Traceable author statement Ref.6. Source: ProtInc

regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.6. Source: ProtInc

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, cholinergic

Traceable author statement Ref.6. Source: ProtInc

transport

Traceable author statement Ref.6. Source: ProtInc

   Cellular_componentacetylcholine-gated channel complex

Traceable author statement Ref.5. Source: ProtInc

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Traceable author statement Ref.6. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionacetylcholine receptor activity

Traceable author statement Ref.6. Source: ProtInc

acetylcholine-activated cation-selective channel activity

Traceable author statement Ref.5. Source: ProtInc

cation transmembrane transporter activity

Traceable author statement Ref.6. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Chain21 – 493473Acetylcholine receptor subunit epsilon
PRO_0000000329

Regions

Topological domain21 – 239219Extracellular Potential
Transmembrane240 – 26425Helical; Potential
Topological domain265 – 2728Cytoplasmic Potential
Transmembrane273 – 29119Helical; Potential
Topological domain292 – 30615Extracellular Potential
Transmembrane307 – 32822Helical; Potential
Topological domain329 – 456128Cytoplasmic Potential
Transmembrane457 – 48024Helical; Potential
Topological domain481 – 49313Extracellular Potential

Amino acid modifications

Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation1611N-linked (GlcNAc...) Potential
Disulfide bond148 ↔ 162 By similarity

Natural variations

Natural variant131G → R in FCCMS; impaired association with alpha CHRNA1 subunit of AChR. Ref.7
VAR_021213
Natural variant181G → V.
Corresponds to variant rs4790235 [ dbSNP | Ensembl ].
VAR_048170
Natural variant981L → P in SCCMS; rare example of recessive inheritance. Ref.10
Corresponds to variant rs28929768 [ dbSNP | Ensembl ].
VAR_019567
Natural variant1411P → L in FCCMS; marked decrease in rate of AChR channel opening; reduction in frequency of open channel state and resistance to desensitization by ACh. Ref.7
VAR_000289
Natural variant1631S → L in FCCMS; fails to assemble with alpha CHRNA1 subunit of AChR. Ref.7
VAR_021214
Natural variant1671R → L in CMS-ACHRD; significantly reduced AChR expression. Ref.8
VAR_000290
Natural variant2411L → F in SCCMS; mild form with variable penetrance. Ref.10
Corresponds to variant rs28999110 [ dbSNP | Ensembl ].
VAR_019568
Natural variant2651P → L in CMS-ACHRD; prolongs burst open duration 2-fold by slowing the rate of channel closing. Ref.8
VAR_000291
Natural variant2841T → P in SCCMS; markedly prolonged channel openings in presence of agonist; as well as opening in the absence of agonist. Ref.5
VAR_000292
Natural variant2891L → F in SCCMS; 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. Ref.4 Ref.6
VAR_000293
Natural variant3311R → W in CMS-ACHRD; 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. Ref.8
VAR_000294
Natural variant4311A → P in FCCMS; causes an increase in distributions of rates for channel opening and closing increasing the range of activation kinetics. Ref.9
VAR_021215

Sequences

Sequence LengthMass (Da)Tools
Q04844 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: A34AF273AF8B31FE

FASTA49354,697
        10         20         30         40         50         60 
MARAPLGVLL LLGLLGRGVG KNEELRLYHH LFNNYDPGSR PVREPEDTVT ISLKVTLTNL 

        70         80         90        100        110        120 
ISLNEKEETL TTSVWIGIDW QDYRLNYSKD DFGGIETLRV PSELVWLPEI VLENNIDGQF 

       130        140        150        160        170        180 
GVAYDANVLV YEGGSVTWLP PAIYRSVCAV EVTYFPFDWQ NCSLIFRSQT YNAEEVEFTF 

       190        200        210        220        230        240 
AVDNDGKTIN KIDIDTEAYT ENGEWAIDFC PGVIRRHHGG ATDGPGETDV IYSLIIRRKP 

       250        260        270        280        290        300 
LFYVINIIVP CVLISGLVLL AYFLPAQAGG QKCTVSINVL LAQTVFLFLI AQKIPETSLS 

       310        320        330        340        350        360 
VPLLGRFLIF VMVVATLIVM NCVIVLNVSQ RTPTTHAMSP RLRHVLLELL PRLLGSPPPP 

       370        380        390        400        410        420 
EAPRAASPPR RASSVGLLLR AEELILKKPR SELVFEGQRH RQGTWTAAFC QSLGAAAPEV 

       430        440        450        460        470        480 
RCCVDAVNFV AESTRDQEAT GEEVSDWVRM GNALDNICFW AALVLFSVGS SLIFLGAYFN 

       490 
RVPDLPYAPC IQP 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of the human muscle acetylcholine receptor. cDNA cloning of the gamma and epsilon subunits."
Beeson D.M.W., Brydson M., Betty M., Jeremiah S., Povey S., Vincent A., Newsom-Davis J.
Eur. J. Biochem. 215:229-238(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Muscle fibroblast.
[2]Abicht A., Stucka R., Lochmuller H.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"A leucine-to-phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow-channel syndrome."
Gomez C.M., Gammack J.T.
Neurology 45:982-985(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCCMS PHE-289.
[5]"Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit."
Ohno K., Hutchinson D.O., Milone M., Brengman J.M., Bouzat C., Sine S.M., Engel A.G.
Proc. Natl. Acad. Sci. U.S.A. 92:758-762(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCCMS PRO-284, CHARACTERIZATION OF VARIANT SCCMS PRO-284.
[6]"New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome."
Engel A.G., Ohno K., Milone M., Wang H.-L., Nakano S., Bouzat C., Pruitt J.N. II, Hutchinson D.O., Brengman J.M., Bren N., Sieb J.P., Sine S.M.
Hum. Mol. Genet. 5:1217-1227(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCCMS PHE-289, CHARACTERIZATION OF VARIANT SCCMS PHE-289.
[7]"Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit."
Ohno K., Wang H.-L., Milone M., Bren N., Brengman J.M., Nakano S., Quiram P., Pruitt J.N. II, Sine S.M., Engel A.G.
Neuron 17:157-170(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FCCMS ARG-13; LEU-141 AND LEU-163, CHARACTERIZATION OF VARIANTS FCCMS ARG-13; LEU-141 AND LEU-163.
[8]"Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations."
Ohno K., Quiram P.A., Milone M., Wang H.-L., Harper M.C., Pruitt J.N. II, Brengman J.M., Pao L., Fischbeck K.H., Crawford T.O., Sine S.M., Engel A.G.
Hum. Mol. Genet. 6:753-766(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMS-ACHRD LEU-167; LEU-265 AND TRP-331, CHARACTERIZATION OF VARIANTS CMS-ACHRD LEU-167; LEU-265 AND TRP-331.
[9]"Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome."
Wang H.-L., Ohno K., Milone M., Brengman J.M., Evoli A., Batocchi A.-P., Middleton L.T., Christodoulou K., Engel A.G., Sine S.M.
J. Gen. Physiol. 116:449-462(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCCMS PRO-431, CHARACTERIZATION OF VARIANT FCCMS PRO-431.
[10]"Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes."
Croxen R., Hatton C., Shelley C., Brydson M., Chauplannaz G., Oosterhuis H., Vincent A., Newsom-Davis J., Colquhoun D., Beeson D.
Neurology 59:162-168(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCCMS PRO-98 AND PHE-241.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66403 mRNA. Translation: CAA47030.1.
AF105999 Genomic DNA. Translation: AAD24503.1.
CH471108 Genomic DNA. Translation: EAW90395.1.
CH471108 Genomic DNA. Translation: EAW90396.1.
CCDSCCDS11058.1.
PIRS34775.
RefSeqNP_000071.1. NM_000080.3.
UniGeneHs.654535.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DF9model-A240-332[»]
ProteinModelPortalQ04844.
SMRQ04844. Positions 22-337, 418-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107567. 1 interaction.
STRING9606.ENSP00000293780.

Chemistry

BindingDBQ04844.
ChEMBLCHEMBL2362997.
GuidetoPHARMACOLOGY477.

Protein family/group databases

TCDB1.A.9.1.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Polymorphism databases

DMDM1168301.

Proteomic databases

PaxDbQ04844.
PRIDEQ04844.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293780; ENSP00000293780; ENSG00000108556.
GeneID1145.
KEGGhsa:1145.
UCSCuc002fzk.1. human.

Organism-specific databases

CTD1145.
GeneCardsGC17M004801.
GeneReviewsCHRNE.
H-InvDBHIX0027273.
HGNCHGNC:1966. CHRNE.
MIM100725. gene.
254200. phenotype.
601462. phenotype.
608930. phenotype.
608931. phenotype.
neXtProtNX_Q04844.
Orphanet98913. Postsynaptic congenital myasthenic syndromes.
PharmGKBPA26498.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG291810.
HOGENOMHOG000006757.
HOVERGENHBG003756.
InParanoidQ04844.
KOK04817.
OMAAIYRSTC.
OrthoDBEOG7H7925.
PhylomeDBQ04844.
TreeFamTF315605.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ04844.
BgeeQ04844.
CleanExHS_CHRNE.
GenevestigatorQ04844.

Family and domain databases

Gene3D1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProIPR027361. 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]
PANTHERPTHR18945. PTHR18945. 1 hit.
PfamPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCHRNE.
GenomeRNAi1145.
NextBio4764.
PROQ04844.
SOURCESearch...

Entry information

Entry nameACHE_HUMAN
AccessionPrimary (citable) accession number: Q04844
Secondary accession number(s): D3DTK6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM