Q04844 (ACHE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetylcholine receptor subunit epsilon

Gene names

Name:	CHRNE
Synonyms:	ACHRE

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	493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 junction › synapse › postsynaptic 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 process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Disease	Congenital myasthenic syndrome Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	muscle contraction Traceable author statement Ref.6. Source: ProtInc regulation of membrane potential Inferred from electronic annotation. Source: Compara synaptic transmission, cholinergic Traceable author statement Ref.6. Source: ProtInc
Cellular_component	acetylcholine-gated channel complex Traceable author statement Ref.5. Source: ProtInc cell junction Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	acetylcholine receptor activity Traceable author statement Ref.6. Source: ProtInc acetylcholine-activated cation-selective channel activity Traceable author statement Ref.5. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20
	Chain	21 – 493	473	Acetylcholine receptor subunit epsilon		PRO_0000000329
Regions
	Topological domain	21 – 239	219	Extracellular Potential
	Transmembrane	240 – 264	25	Helical; Potential
	Topological domain	265 – 272	8	Cytoplasmic Potential
	Transmembrane	273 – 291	19	Helical; Potential
	Topological domain	292 – 306	15	Extracellular Potential
	Transmembrane	307 – 328	22	Helical; Potential
	Topological domain	329 – 456	128	Cytoplasmic Potential
	Transmembrane	457 – 480	24	Helical; Potential
	Topological domain	481 – 493	13	Extracellular Potential
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Disulfide bond	148 ↔ 162		By similarity
Natural variations
	Natural variant	13	1	G → R in FCCMS; impaired association with alpha CHRNA1 subunit of AChR. Ref.7		VAR_021213
	Natural variant	18	1	G → V. Corresponds to variant rs4790235 [ dbSNP | Ensembl ].		VAR_048170
	Natural variant	98	1	L → P in SCCMS; rare example of recessive inheritance. Ref.10 Corresponds to variant rs28929768 [ dbSNP | Ensembl ].		VAR_019567
	Natural variant	141	1	P → 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 variant	163	1	S → L in FCCMS; fails to assemble with alpha CHRNA1 subunit of AChR. Ref.7		VAR_021214
	Natural variant	167	1	R → L in CMS-ACHRD; significantly reduced AChR expression. Ref.8		VAR_000290
	Natural variant	241	1	L → F in SCCMS; mild form with variable penetrance. Ref.10 Corresponds to variant rs28999110 [ dbSNP | Ensembl ].		VAR_019568
	Natural variant	265	1	P → L in CMS-ACHRD; prolongs burst open duration 2-fold by slowing the rate of channel closing. Ref.8		VAR_000291
	Natural variant	284	1	T → 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 variant	289	1	L → 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 variant	331	1	R → 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 variant	431	1	A → 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		Length	Mass (Da)
	Q04844 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: A34AF273AF8B31FE	FASTA	493	54,697
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

GeneReviews

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.

IPI

IPI00029753.

PIR

S34775.

RefSeq

NP_000071.1. NM_000080.3.

UniGene

Hs.654535.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DF9	model	-	A	240-332	[»]

ProteinModelPortal

Q04844.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000293780.

Polymorphism databases

DMDM

1168301.

Proteomic databases

PaxDb

Q04844.

PRIDE

Q04844.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000293780; ENSP00000293780; ENSG00000108556.

GeneID

1145.

KEGG

hsa:1145.

UCSC

uc002fzk.1. human.

Organism-specific databases

CTD

1145.

GeneCards

GC17M004801.

H-InvDB

HIX0027273.

HGNC

HGNC:1966. CHRNE.

MIM

100725. gene.
254200. phenotype.
601462. phenotype.
608930. phenotype.
608931. phenotype.

neXtProt

NX_Q04844.

Orphanet

98913. Postsynaptic congenital myasthenic syndromes.

PharmGKB

PA26498.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG291810.

HOGENOM

HOG000006757.

HOVERGEN

HBG003756.

InParanoid

Q04844.

KO

K04817.

OMA

AIYRSTC.

OrthoDB

EOG4DZ1V6.

PhylomeDB

Q04844.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q04844.

Bgee

Q04844.

CleanEx

HS_CHRNE.

Genevestigator

Q04844.

GermOnline

ENSG00000108556. Homo sapiens.

Family and domain databases

Gene3D

2.70.170.10. 1 hit.

InterPro

IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
IPR002394. Nicotinic_acetylcholine_rcpt.
[Graphical view]

PANTHER

PTHR18945. PTHR18945. 1 hit.

Pfam

PF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]

PRINTS

PR00254. NICOTINICR.
PR00252. NRIONCHANNEL.

SUPFAM

SSF90112. Neu_channel_TM. 1 hit.
SSF63712. Neur_chan_LBD. 1 hit.

PROSITE

PS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q04844.

ChEMBL

CHEMBL2484.

GenomeRNAi

1145.

NextBio

4764.

SOURCE

Search...

Entry information

Entry name

ACHE_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 126 of the entry and version 2 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.