Q07001 (ACHD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetylcholine receptor subunit delta

Gene names

Name:	CHRND
Synonyms:	ACHRD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	517 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	Defects in CHRND are a cause of multiple pterygium syndrome lethal type (MUPSL) [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. Ref.9 Defects in CHRND are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most 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. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes. Ref.4 Ref.5 Defects in CHRND are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due 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.
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Delta/CHRND 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	Ionic channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	muscle contraction Traceable author statement. Source: ProtInc musculoskeletal movement Inferred from mutant phenotype Ref.9. Source: BHF-UCL neuromuscular process Non-traceable author statement Ref.9. Source: BHF-UCL signal transduction Traceable author statement. Source: ProtInc skeletal muscle tissue growth Inferred from mutant phenotype Ref.9. Source: BHF-UCL synaptic transmission Traceable author statement. Source: Reactome
Cellular component	acetylcholine-gated channel complex Traceable author statement. Source: ProtInc cell junction Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic membrane Non-traceable author statement Ref.9. Source: BHF-UCL
Molecular function	acetylcholine-activated cation-selective channel activity Traceable author statement. Source: ProtInc receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	By similarity
	Chain	22 – 517	496	Acetylcholine receptor subunit delta		PRO_0000000322
Regions
	Topological domain	22 – 245	224	Extracellular Potential
	Transmembrane	246 – 270	25	Helical; Potential
	Transmembrane	278 – 299	22	Helical; Potential
	Transmembrane	312 – 333	22	Helical; Potential
	Topological domain	334 – 471	138	Cytoplasmic Potential
	Transmembrane	472 – 490	19	Helical; Potential
Amino acid modifications
	Modified residue	390	1	Phosphotyrosine; by Tyr-kinases By similarity
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Disulfide bond	151 ↔ 165		By similarity
Natural variations
	Natural variant	80	1	E → K in FCCMS; reduced adult and fetal AChR expression and a reduced probability of both adult and fetal AChR being in the open state. Ref.6		VAR_021210
	Natural variant	95	1	F → L in MUPSL. Ref.9		VAR_043905
	Natural variant	271	1	P → Q in FCCMS; burst duration was decreased and disassociation of ACh was increased resulting in brief channel opening episodes; shows abnormal association with alpha CHRNA1 subunit resulting in a decreased number of fully assembled AChRs. Ref.7		VAR_021211
	Natural variant	288	1	Q → E in SCCMS; a benign mutation or a rare polymorphism. Ref.4 Corresponds to variant rs41265127 [ dbSNP | Ensembl ].		VAR_021212
	Natural variant	289	1	S → F in SCCMS; delayed closure of AchR ion channels, increasing the propensity for open-channel block, as well as a reduced rate of channel opening. Ref.5		VAR_019566
	Natural variant	398	1	D → E in a breast cancer sample; somatic mutation. Ref.8		VAR_036031

Sequences

	Sequence		Length	Mass (Da)
	Q07001 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 195CEF69358758BD	FASTA	517	58,895
	10 20 30 40 50 60 MEGPVLTLGL LAALAVCGSW GLNEEERLIR HLFQEKGYNK ELRPVAHKEE SVDVALALTL 70 80 90 100 110 120 SNLISLKEVE ETLTTNVWIE HGWTDNRLKW NAEEFGNISV LRLPPDMVWL PEIVLENNND 130 140 150 160 170 180 GSFQISYSCN VLVYHYGFVY WLPPAIFRSS CPISVTYFPF DWQNCSLKFS SLKYTAKEIT 190 200 210 220 230 240 LSLKQDAKEN RTYPVEWIII DPEGFTENGE WEIVHRPARV NVDPRAPLDS PSRQDITFYL 250 260 270 280 290 300 IIRRKPLFYI INILVPCVLI SFMVNLVFYL PADSGEKTSV AISVLLAQSV FLLLISKRLP 310 320 330 340 350 360 ATSMAIPLIG KFLLFGMVLV TMVVVICVIV LNIHFRTPST HVLSEGVKKL FLETLPELLH 370 380 390 400 410 420 MSRPAEDGPS PGALVRRSSS LGYISKAEEY FLLKSRSDLM FEKQSERHGL ARRLTTARRP 430 440 450 460 470 480 PASSEQAQQE LFNELKPAVD GANFIVNHMR DQNNYNEEKD SWNRVARTVD RLCLFVVTPV 490 500 510 MVVGTAWIFL QGVYNQPPPQ PFPGDPYSYN VQDKRFI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A muscle acetylcholine receptor is expressed in the human cerebellar medulloblastoma cell line TE671." Luther M.A., Schoepfer R., Whiting P., Casey B., Blatt Y., Montal M.S., Montal M., Lindstrom J. J. Neurosci. 9:1082-1096(1989) [PubMed: 2564429] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart and Lung.
[4]	"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: 8872460] [Abstract] Cited for: VARIANT SCCMS GLU-288.
[5]	"Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms." Gomez C.M., Maselli R.A., Vohra B.P.S., Navedo M., Stiles J.R., Charnet P., Schott K., Rojas L., Keesey J., Verity A., Wollmann R.W., Lasalde-Dominicci J. Ann. Neurol. 51:102-112(2002) [PubMed: 11782989] [Abstract] Cited for: VARIANT SCCMS PHE-289, CHARACTERIZATION OF VARIANT SCCMS PHE-289.
[6]	"Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita." Brownlow S., Webster R., Croxen R., Brydson M., Neville B., Lin J.-P., Vincent A., Newsom-Davis J., Beeson D. J. Clin. Invest. 108:125-130(2001) [PubMed: 11435464] [Abstract] Cited for: VARIANT FCCMS LYS-80, CHARACTERIZATION OF VARIANT FCCMS LYS-80.
[7]	"Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation." Shen X.-M., Ohno K., Fukudome T., Tsujino A., Brengman J.M., De Vivo D.C., Packer R.J., Engel A.G. Neurology 59:1881-1888(2002) [PubMed: 12499478] [Abstract] Cited for: VARIANT FCCMS GLN-271, CHARACTERIZATION OF VARIANT FCCMS GLN-271.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-398.
[9]	"Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders." Michalk A., Stricker S., Becker J., Rupps R., Pantzar T., Miertus J., Botta G., Naretto V.G., Janetzki C., Yaqoob N., Ott C.-E., Seelow D., Wieczorek D., Fiebig B., Wirth B., Hoopmann M., Walther M., Koerber F. , Blankenburg M., Mundlos S., Heller R., Hoffmann K. Am. J. Hum. Genet. 82:464-476(2008) [PubMed: 18252226] [Abstract] Cited for: VARIANT MUPSL LEU-95.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X55019 mRNA. Translation: CAA38759.1. AC092165 Genomic DNA. Translation: AAY24102.1. BC093923 mRNA. Translation: AAH93923.1. BC093925 mRNA. Translation: AAH93925.1.
IPI	IPI00014192.
PIR	A60916.
RefSeq	NP_000742.1. NM_000751.1.
UniGene	Hs.156289.
3D structure databases
ProteinModelPortal	Q07001.
SMR	Q07001. Positions 22-500.
ModBase	Search...
Protein-protein interaction databases
STRING	Q07001.
PTM databases
PhosphoSite	Q07001.
Polymorphism databases
DMDM	543759.
Proteomic databases
PRIDE	Q07001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258385; ENSP00000258385; ENSG00000135902.
GeneID	1144.
KEGG	hsa:1144.
UCSC	uc002vsw.1. human.
Organism-specific databases
CTD	1144.
GeneCards	GC02P233390.
H-InvDB	HIX0030011.
HGNC	HGNC:1965. CHRND.
MIM	100720. gene. 253290. phenotype. 601462. phenotype. 608930. phenotype.
neXtProt	NX_Q07001.
Orphanet	33108. Lethal multiple pterygium syndrome. 98913. Postsynaptic congenital myasthenic syndromes.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04514.
GeneTree	ENSGT00590000082904.
HOGENOM	HBG387619.
HOVERGEN	HBG003756.
InParanoid	Q07001.
OMA	FIVNHMR.
PhylomeDB	Q07001.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q07001.
Bgee	Q07001.
CleanEx	HS_CHRND.
Genevestigator	Q07001.
GermOnline	ENSG00000135902. Homo sapiens.
Family and domain databases
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]
Gene3D	G3DSA:2.70.170.10. Neur_chan_lig_bd. 1 hit.
KO	K04816.
PANTHER	PTHR18945. Neur_channel. 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.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	4760.
SOURCE	Search...

Entry information

Entry name

ACHD_HUMAN

Accession

Primary (citable) accession number: Q07001
Secondary accession number(s): Q52LH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 115 of the entry and version 1 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.