P30532 (ACHA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuronal acetylcholine receptor subunit alpha-5

Gene names

Name:	CHRNA5
Synonyms:	NACHRA5

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	468 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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	Neuronal AChR seems to be composed of two different type of subunits: alpha and non-alpha (beta).
Subcellular location	Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
Polymorphism	Genetic variations in CHRNA5 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 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
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to nicotine Inferred from mutant phenotype PubMed 18227835. Source: UniProtKB
Cellular_component	acetylcholine-gated channel complex Inferred by curator Ref.1. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	acetylcholine receptor activity Inferred from direct assay Ref.1. Source: UniProtKB acetylcholine-activated cation-selective channel activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 468	446	Neuronal acetylcholine receptor subunit alpha-5		PRO_0000000356
Regions
	Topological domain	23 – 254	232	Extracellular Potential
	Transmembrane	255 – 275	21	Helical; Potential
	Transmembrane	282 – 302	21	Helical; Potential
	Transmembrane	317 – 337	21	Helical; Potential
	Topological domain	338 – 429	92	Cytoplasmic Potential
	Transmembrane	430 – 451	22	Helical; Potential
	Topological domain	452 – 468	17	Extracellular Potential
Amino acid modifications
	Glycosylation	155	1	N-linked (GlcNAc...) Potential
	Glycosylation	183	1	N-linked (GlcNAc...) Potential
	Glycosylation	229	1	N-linked (GlcNAc...) Potential
	Disulfide bond	170 ↔ 184		By similarity
	Disulfide bond	234 ↔ 235		Associated with receptor activation By similarity
Natural variations
	Natural variant	134	1	V → I. Corresponds to variant rs2229961 [ dbSNP | Ensembl ].		VAR_046211
	Natural variant	398	1	D → N Associated with susceptibility to lung cancer. Ref.2 Ref.4 Corresponds to variant rs16969968 [ dbSNP | Ensembl ].		VAR_046212
Experimental info
	Sequence conflict	23 – 34	12	RCGLA…AGGAQ → ALRSSRARRAAR in AAA58357. Ref.1
	Sequence conflict	128	1	V → S in AAA58357. Ref.1
	Sequence conflict	365	1	C → S in AAA58357. Ref.1
	Sequence conflict	405	1	R → T in AAA58357. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P30532 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 7FE91A2E362289C0	FASTA	468	53,054
	10 20 30 40 50 60 MAARGSGPRA LRLLLLVQLV AGRCGLAGAA GGAQRGLSEP SSIAKHEDSL LKDLFQDYER 70 80 90 100 110 120 WVRPVEHLND KIKIKFGLAI SQLVDVDEKN QLMTTNVWLK QEWIDVKLRW NPDDYGGIKV 130 140 150 160 170 180 IRVPSDSVWT PDIVLFDNAD GRFEGTSTKT VIRYNGTVTW TPPANYKSSC TIDVTFFPFD 190 200 210 220 230 240 LQNCSMKFGS WTYDGSQVDI ILEDQDVDKR DFFDNGEWEI VSATGSKGNR TDSCCWYPYV 250 260 270 280 290 300 TYSFVIKRLP LFYTLFLIIP CIGLSFLTVL VFYLPSNEGE KICLCTSVLV SLTVFLLVIE 310 320 330 340 350 360 EIIPSSSKVI PLIGEYLVFT MIFVTLSIMV TVFAINIHHR SSSTHNAMAP LVRKIFLHTL 370 380 390 400 410 420 PKLLCMRSHV DRYFTQKEET ESGSGPKSSR NTLEAALDSI RYITRHIMKE NDVREVVEDW 430 440 450 460 KFIAQVLDRM FLWTFLFVSI VGSLGLFVPV IYKWANILIP VHIGNANK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neuronal-type alpha-bungarotoxin receptors and the alpha 5-nicotinic receptor subunit gene are expressed in neuronal and nonneuronal human cell lines." Chini B., Clementi F., Hukovic N., Sher E. Proc. Natl. Acad. Sci. U.S.A. 89:1572-1576(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits." Elliott K.J., Ellis S.B., Berckhan K.J., Urrutia A., Chavez-Noriega L.E., Johnson E.C., Velicelebi G., Harpold M.M. J. Mol. Neurosci. 7:217-228(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-398.
[3]	"Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32." Groot Kormelink P.J., Luyten W.H.M.L. FEBS Lett. 400:309-314(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Characterization of the genomic structure of human nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: identification of two novel introns in the 3' untranslated region of CHRNA3 and of a tail-to-tail overlap between CHRNA3 and CHRNA5." Duga S., Solda G., Asselta R., Bonati M.T., Dalpra L., Malcovati M., Tenchini M.L. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-398.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"Genomics: when the smoke clears." Chanock S.J., Hunter D.J. Nature 452:537-538(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SQTL3 AND LUNG CANCER.
[7]	"A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25." Hung R.J., McKay J.D., Gaborieau V., Boffetta P., Hashibe M., Zaridze D., Mukeria A., Szeszenia-Dabrowska N., Lissowska J., Rudnai P., Fabianova E., Mates D., Bencko V., Foretova L., Janout V., Chen C., Goodman G., Field J.K. , Liloglou T., Xinarianos G., Cassidy A., McLaughlin J., Liu G., Narod S., Krokan H.E., Skorpen F., Elvestad M.B., Hveem K., Vatten L., Linseisen J., Clavel-Chapelon F., Vineis P., Bueno-de-Mesquita H.B., Lund E., Martinez C., Bingham S., Rasmuson T., Hainaut P., Riboli E., Ahrens W., Benhamou S., Lagiou P., Trichopoulos D., Holcatova I., Merletti F., Kjaerheim K., Agudo A., Macfarlane G., Talamini R., Simonato L., Lowry R., Conway D.I., Znaor A., Healy C., Zelenika D., Boland A., Delepine M., Foglio M., Lechner D., Matsuda F., Blanche H., Gut I., Heath S., Lathrop M., Brennan P. Nature 452:633-637(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SQTL3 AND LUNG CANCER.
[8]	"Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1." Amos C.I., Wu X., Broderick P., Gorlov I.P., Gu J., Eisen T., Dong Q., Zhang Q., Gu X., Vijayakrishnan J., Sullivan K., Matakidou A., Wang Y., Mills G., Doheny K., Tsai Y.-Y., Chen W.V., Shete S., Spitz M.R., Houlston R.S. Nat. Genet. 40:616-622(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SQTL3 AND LUNG CANCER.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M83712 mRNA. Translation: AAA58357.1. U62434 mRNA. Translation: AAB40112.1. Y08419 mRNA. Translation: CAA69696.1. AJ306481 , AJ306482, AJ306483, AJ306484, AJ306485, AJ306486 Genomic DNA. Translation: CAC34820.1. BC033639 mRNA. Translation: AAH33639.1.
IPI	IPI00295323.
PIR	A38223.
RefSeq	NP_000736.2. NM_000745.3.
UniGene	Hs.1614. Hs.719767.
3D structure databases
ProteinModelPortal	P30532.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000299565.
PTM databases
PhosphoSite	P30532.
Polymorphism databases
DMDM	2506126.
Proteomic databases
PaxDb	P30532.
PRIDE	P30532.
Protocols and materials databases
DNASU	1138.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299565; ENSP00000299565; ENSG00000169684.
GeneID	1138.
KEGG	hsa:1138.
UCSC	uc002bdy.3. human.
Organism-specific databases
CTD	1138.
GeneCards	GC15P078857.
HGNC	HGNC:1959. CHRNA5.
HPA	HPA054381.
MIM	118505. gene. 612052. phenotype.
neXtProt	NX_P30532.
PharmGKB	PA26491.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG267611.
HOGENOM	HOG000006756.
HOVERGEN	HBG003756.
InParanoid	P30532.
KO	K04807.
OMA	WANILIP.
OrthoDB	EOG41JZC6.
PhylomeDB	P30532.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P30532.
Bgee	P30532.
CleanEx	HS_CHRNA5.
Genevestigator	P30532.
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. 2 hits. [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
BindingDB	P30532.
ChEMBL	CHEMBL2454.
GenomeRNAi	1138.
NextBio	4734.
SOURCE	Search...

Entry information

Entry name

ACHA5_HUMAN

Accession

Primary (citable) accession number: P30532
Secondary accession number(s): Q15824, Q99554

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 131 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.