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Protein

Neuronal acetylcholine receptor subunit alpha-5

Gene

CHRNA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.

GO - Molecular functioni

  • acetylcholine-activated cation-selective channel activity Source: UniProtKB
  • acetylcholine receptor activity Source: UniProtKB
  • ligand-gated ion channel activity Source: DFLAT

GO - Biological processi

  • behavioral response to nicotine Source: UniProtKB
  • cation transmembrane transport Source: GOC
  • cation transport Source: GOC
  • ion transmembrane transport Source: GOC
  • signal transduction Source: UniProtKB
  • synaptic transmission Source: UniProtKB
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiREACT_22303. Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
REACT_22352. Highly calcium permeable nicotinic acetylcholine receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal acetylcholine receptor subunit alpha-5
Gene namesi
Name:CHRNA5
Synonyms:NACHRA5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:1959. CHRNA5.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 254232ExtracellularSequence AnalysisAdd
BLAST
Transmembranei255 – 27521HelicalSequence AnalysisAdd
BLAST
Transmembranei282 – 30221HelicalSequence AnalysisAdd
BLAST
Transmembranei317 – 33721HelicalSequence AnalysisAdd
BLAST
Topological domaini338 – 42992CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei430 – 45122HelicalSequence AnalysisAdd
BLAST
Topological domaini452 – 46817ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • acetylcholine-gated channel complex Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • plasma membrane Source: Reactome
  • postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

MIMi612052. phenotype.
PharmGKBiPA26491.

Chemistry

DrugBankiDB00674. Galantamine.
DB00184. Nicotine.

Polymorphism and mutation databases

BioMutaiCHRNA5.
DMDMi2506126.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Chaini23 – 468446Neuronal acetylcholine receptor subunit alpha-5PRO_0000000356Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi155 – 1551N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi170 ↔ 184By similarity
Glycosylationi183 – 1831N-linked (GlcNAc...)Sequence Analysis
Glycosylationi229 – 2291N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi234 ↔ 235Associated with receptor activationBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP30532.
PaxDbiP30532.
PRIDEiP30532.

PTM databases

PhosphoSiteiP30532.

Expressioni

Gene expression databases

BgeeiP30532.
CleanExiHS_CHRNA5.
ExpressionAtlasiP30532. baseline and differential.
GenevisibleiP30532. HS.

Organism-specific databases

HPAiHPA054381.

Interactioni

Subunit structurei

Neuronal AChR seems to be composed of two different type of subunits: alpha and non-alpha (beta).

Protein-protein interaction databases

BioGridi107560. 7 interactions.
IntActiP30532. 1 interaction.
STRINGi9606.ENSP00000299565.

Structurei

3D structure databases

ProteinModelPortaliP30532.
SMRiP30532. Positions 44-447.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG267611.
GeneTreeiENSGT00760000118930.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiP30532.
KOiK04807.
OMAiVHIGNAN.
OrthoDBiEOG72JWGV.
PhylomeDBiP30532.
TreeFamiTF315605.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR027361. 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]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P30532-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAARGSGPRA LRLLLLVQLV AGRCGLAGAA GGAQRGLSEP SSIAKHEDSL
60 70 80 90 100
LKDLFQDYER WVRPVEHLND KIKIKFGLAI SQLVDVDEKN QLMTTNVWLK
110 120 130 140 150
QEWIDVKLRW NPDDYGGIKV IRVPSDSVWT PDIVLFDNAD GRFEGTSTKT
160 170 180 190 200
VIRYNGTVTW TPPANYKSSC TIDVTFFPFD LQNCSMKFGS WTYDGSQVDI
210 220 230 240 250
ILEDQDVDKR DFFDNGEWEI VSATGSKGNR TDSCCWYPYV TYSFVIKRLP
260 270 280 290 300
LFYTLFLIIP CIGLSFLTVL VFYLPSNEGE KICLCTSVLV SLTVFLLVIE
310 320 330 340 350
EIIPSSSKVI PLIGEYLVFT MIFVTLSIMV TVFAINIHHR SSSTHNAMAP
360 370 380 390 400
LVRKIFLHTL PKLLCMRSHV DRYFTQKEET ESGSGPKSSR NTLEAALDSI
410 420 430 440 450
RYITRHIMKE NDVREVVEDW KFIAQVLDRM FLWTFLFVSI VGSLGLFVPV
460
IYKWANILIP VHIGNANK
Length:468
Mass (Da):53,054
Last modified:November 1, 1997 - v2
Checksum:i7FE91A2E362289C0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 3412RCGLA…AGGAQ → ALRSSRARRAAR in AAA58357 (PubMed:1542648).CuratedAdd
BLAST
Sequence conflicti128 – 1281V → S in AAA58357 (PubMed:1542648).Curated
Sequence conflicti365 – 3651C → S in AAA58357 (PubMed:1542648).Curated
Sequence conflicti405 – 4051R → T in AAA58357 (PubMed:1542648).Curated

Polymorphismi

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) [MIMi:612052].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti134 – 1341V → I.
Corresponds to variant rs2229961 [ dbSNP | Ensembl ].
VAR_046211
Natural varianti398 – 3981D → N Associated with susceptibility to lung cancer. 2 Publications
Corresponds to variant rs16969968 [ dbSNP | Ensembl ].
VAR_046212

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10304.1.
PIRiA38223.
RefSeqiNP_000736.2. NM_000745.3.
UniGeneiHs.1614.
Hs.719767.

Genome annotation databases

EnsembliENST00000299565; ENSP00000299565; ENSG00000169684.
GeneIDi1138.
KEGGihsa:1138.
UCSCiuc002bdy.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10304.1.
PIRiA38223.
RefSeqiNP_000736.2. NM_000745.3.
UniGeneiHs.1614.
Hs.719767.

3D structure databases

ProteinModelPortaliP30532.
SMRiP30532. Positions 44-447.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107560. 7 interactions.
IntActiP30532. 1 interaction.
STRINGi9606.ENSP00000299565.

Chemistry

BindingDBiP30532.
ChEMBLiCHEMBL2221346.
DrugBankiDB00674. Galantamine.
DB00184. Nicotine.
GuidetoPHARMACOLOGYi466.

PTM databases

PhosphoSiteiP30532.

Polymorphism and mutation databases

BioMutaiCHRNA5.
DMDMi2506126.

Proteomic databases

MaxQBiP30532.
PaxDbiP30532.
PRIDEiP30532.

Protocols and materials databases

DNASUi1138.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299565; ENSP00000299565; ENSG00000169684.
GeneIDi1138.
KEGGihsa:1138.
UCSCiuc002bdy.3. human.

Organism-specific databases

CTDi1138.
GeneCardsiGC15P078857.
HGNCiHGNC:1959. CHRNA5.
HPAiHPA054381.
MIMi118505. gene.
612052. phenotype.
neXtProtiNX_P30532.
PharmGKBiPA26491.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG267611.
GeneTreeiENSGT00760000118930.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiP30532.
KOiK04807.
OMAiVHIGNAN.
OrthoDBiEOG72JWGV.
PhylomeDBiP30532.
TreeFamiTF315605.

Enzyme and pathway databases

ReactomeiREACT_22303. Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
REACT_22352. Highly calcium permeable nicotinic acetylcholine receptors.

Miscellaneous databases

GeneWikiiCHRNA5.
GenomeRNAii1138.
NextBioi4734.
PROiP30532.
SOURCEiSearch...

Gene expression databases

BgeeiP30532.
CleanExiHS_CHRNA5.
ExpressionAtlasiP30532. baseline and differential.
GenevisibleiP30532. HS.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR027361. 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]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: INVOLVEMENT IN SQTL3 AND LUNG CANCER.

Entry informationi

Entry nameiACHA5_HUMAN
AccessioniPrimary (citable) accession number: P30532
Secondary accession number(s): Q15824, Q99554
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1997
Last modified: June 24, 2015
This is version 149 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.