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UniProtKB - P32297 (ACHA3_HUMAN)

Protein

Neuronal acetylcholine receptor subunit alpha-3

Gene

CHRNA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 binding Source: UniProtKB
  • acetylcholine-gated cation-selective channel activity Source: UniProtKB
  • acetylcholine receptor activity Source: UniProtKB
  • ligand-gated ion channel activity Source: DFLAT
  • serotonin-gated cation-selective channel activity Source: GO_Central
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-629587 Highly sodium permeable acetylcholine nicotinic receptors
R-HSA-629594 Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597 Highly calcium permeable nicotinic acetylcholine receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal acetylcholine receptor subunit alpha-3
Gene namesi
Name:CHRNA3
Synonyms:NACHRA3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000080644.15
HGNCiHGNC:1957 CHRNA3
MIMi118503 gene
neXtProtiNX_P32297

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 240ExtracellularSequence analysisAdd BLAST209
Transmembranei241 – 265HelicalSequence analysisAdd BLAST25
Transmembranei273 – 291HelicalSequence analysisAdd BLAST19
Transmembranei307 – 328HelicalSequence analysisAdd BLAST22
Topological domaini329 – 477CytoplasmicSequence analysisAdd BLAST149
Transmembranei478 – 497HelicalSequence analysisAdd BLAST20

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi1136
MalaCardsiCHRNA3
MIMi612052 phenotype
OpenTargetsiENSG00000080644
PharmGKBiPA113

Chemistry databases

ChEMBLiCHEMBL3068
DrugBankiDB01156 Bupropion
DB09028 Cytisine
DB00514 Dextromethorphan
DB00898 Ethanol
DB00674 Galantamine
DB00848 Levamisole
DB01227 Levomethadyl Acetate
DB00184 Nicotine
DB01090 Pentolinium
DB01273 Varenicline
GuidetoPHARMACOLOGYi464

Polymorphism and mutation databases

BioMutaiCHRNA3
DMDMi254763435

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000000034632 – 505Neuronal acetylcholine receptor subunit alpha-3Add BLAST474

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi55N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi159 ↔ 173By similarity
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi223 ↔ 224Associated with receptor activationBy similarity
Modified residuei413PhosphoserineBy similarity1
Modified residuei416PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP32297
PeptideAtlasiP32297
PRIDEiP32297
ProteomicsDBi54858
54859 [P32297-1]
54860 [P32297-3]

PTM databases

iPTMnetiP32297
PhosphoSitePlusiP32297

Expressioni

Gene expression databases

BgeeiENSG00000080644 Expressed in 125 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_CHRNA3
ExpressionAtlasiP32297 baseline and differential
GenevisibleiP32297 HS

Organism-specific databases

HPAiHPA029430

Interactioni

Subunit structurei

Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-3 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors. Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019). The heteropentamer alpha-3-beta-2 interacts with alpha-conotoxins ImI and ImII (PubMed:15609996). The heteropentamer alpha-3-beta-2 interacts with alpha-conotoxins ImI, ImII, PnIA, GID and MII (By similarity). The heteropentamer alpha-3-beta-4 interacts with the alpha-conotoxin ImI (PubMed:15609996).By similarity3 Publications

Protein-protein interaction databases

BioGridi107558, 31 interactors
ComplexPortaliCPX-187 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2
CPX-210 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4
CPX-213 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4
CPX-2192 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3
CPX-2193 Neuronal nicotinic acetylcholine receptor complex, alpha3-beta2
CPX-2200 Neuronal nicotinic acetylcholine receptor complex, alpha3-beta4
IntActiP32297, 3 interactors
STRINGi9606.ENSP00000315602

Chemistry databases

BindingDBiP32297

Structurei

Secondary structure

1505
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP32297
SMRiP32297
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-3/CHRNA3 sub-subfamily. [View classification]Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3645 Eukaryota
ENOG410XQGR LUCA
GeneTreeiENSGT00760000118930
HOVERGENiHBG003756
InParanoidiP32297
KOiK04805
OMAiQPLMARD
OrthoDBiEOG091G0R20
PhylomeDBiP32297
TreeFamiTF315605

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
IPR002394 Nicotinic_acetylcholine_rcpt
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR00254 NICOTINICR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 2 (identifier: P32297-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGSGPLSLPL ALSPPRLLLL LLLSLLPVAR ASEAEHRLFE RLFEDYNEII 
        60         70         80         90        100
RPVANVSDPV IIHFEVSMSQ LVKVDEVNQI METNLWLKQI WNDYKLKWNP 
       110        120        130        140        150
SDYGGAEFMR VPAQKIWKPD IVLYNNAVGD FQVDDKTKAL LKYTGEVTWI 
       160        170        180        190        200
PPAIFKSSCK IDVTYFPFDY QNCTMKFGSW SYDKAKIDLV LIGSSMNLKD 
       210        220        230        240        250
YWESGEWAII KAPGYKHDIK YNCCEEIYPD ITYSLYIRRL PLFYTINLII 
       260        270        280        290        300
PCLLISFLTV LVFYLPSDCG EKVTLCISVL LSLTVFLLVI TETIPSTSLV 
       310        320        330        340        350
IPLIGEYLLF TMIFVTLSIV ITVFVLNVHY RTPTTHTMPS WVKTVFLNLL 
       360        370        380        390        400
PRVMFMTRPT SNEGNAQKPR PLYGAELSNL NCFSRAESKG CKEGYPCQDG 
       410        420        430        440        450
MCGYCHHRRI KISNFSANLT RSSSSESVDA VLSLSALSPE IKEAIQSVKY 
       460        470        480        490        500
IAENMKAQNE AKEIQDDWKY VAMVIDRIFL WVFTLVCILG TAGLFLQPLM 

AREDA
Length:505
Mass (Da):57,480
Last modified:July 28, 2009 - v4
Checksum:i478D7712D59ACB2D
GO
Isoform 1 (identifier: P32297-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MGSGPL → MALAV

Show »
Length:504
Mass (Da):57,423
Checksum:iF4D2DA153F2B3476
GO
Isoform 3 (identifier: P32297-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     464-505: IQDDWKYVAMVIDRIFLWVFTLVCILGTAGLFLQPLMAREDA → EQKAQEIQQLKRKEKSTETSDQEPGL

Show »
Length:489
Mass (Da):55,637
Checksum:iF8C4F79BDC30A44E
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YNF9H0YNF9_HUMAN
Neuronal acetylcholine receptor sub...
CHRNA3
17Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5 – 14PLSLPLALSP → ALAAPGAVA in AAA59942 (PubMed:1989896).Curated10
Sequence conflicti12 – 15LSPP → CRA in AAC84176 (PubMed:2336208).Curated4
Sequence conflicti102D → G in AAC84176 (PubMed:2336208).Curated1
Sequence conflicti134 – 135DD → TT in AAC84176 (PubMed:2336208).Curated2
Sequence conflicti237I → S in AAC84176 (PubMed:2336208).Curated1
Sequence conflicti432L → V in AAC84176 (PubMed:2336208).Curated1

Polymorphismi

Genetic variations in CHRNA3 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_01324023Missing 4 Publications1
Natural variantiVAR_05911037R → H. Corresponds to variant dbSNP:rs8192475Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0377501 – 6MGSGPL → MALAV in isoform 1. 3 Publications6
Alternative sequenceiVSP_037751464 – 505IQDDW…AREDA → EQKAQEIQQLKRKEKSTETS DQEPGL in isoform 3. 2 PublicationsAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86383 mRNA Translation: AAC84176.1
M37981 mRNA Translation: AAA59942.1
U62432 mRNA Translation: AAB40110.1
Y08418 mRNA Translation: CAA69695.1
AJ007783
, AJ007784, AJ007785, AJ007786, AJ007787 Genomic DNA Translation: CAA07682.1
BT006646 mRNA Translation: AAP35292.1
BT006897 mRNA Translation: AAP35543.1
AC027228 Genomic DNA No translation available.
AC067863 Genomic DNA No translation available.
BC000513 mRNA Translation: AAH00513.1
BC001642 mRNA Translation: AAH01642.1
BC002996 mRNA Translation: AAH02996.1
BC006114 mRNA Translation: AAH06114.1
BC098443 mRNA Translation: AAH98443.1
AF385584 mRNA Translation: AAK68110.1
X53559 mRNA Translation: CAA37625.1
CCDSiCCDS10305.1 [P32297-2]
CCDS53964.1 [P32297-3]
PIRiA37040
A53956
RefSeqiNP_000734.2, NM_000743.4 [P32297-2]
NP_001160166.1, NM_001166694.1 [P32297-3]
UniGeneiHs.89605

Genome annotation databases

EnsembliENST00000326828; ENSP00000315602; ENSG00000080644 [P32297-2]
ENST00000348639; ENSP00000267951; ENSG00000080644 [P32297-3]
ENST00000559658; ENSP00000452896; ENSG00000080644 [P32297-2]
GeneIDi1136
KEGGihsa:1136
UCSCiuc002beb.4 human [P32297-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86383 mRNA Translation: AAC84176.1
M37981 mRNA Translation: AAA59942.1
U62432 mRNA Translation: AAB40110.1
Y08418 mRNA Translation: CAA69695.1
AJ007783
, AJ007784, AJ007785, AJ007786, AJ007787 Genomic DNA Translation: CAA07682.1
BT006646 mRNA Translation: AAP35292.1
BT006897 mRNA Translation: AAP35543.1
AC027228 Genomic DNA No translation available.
AC067863 Genomic DNA No translation available.
BC000513 mRNA Translation: AAH00513.1
BC001642 mRNA Translation: AAH01642.1
BC002996 mRNA Translation: AAH02996.1
BC006114 mRNA Translation: AAH06114.1
BC098443 mRNA Translation: AAH98443.1
AF385584 mRNA Translation: AAK68110.1
X53559 mRNA Translation: CAA37625.1
CCDSiCCDS10305.1 [P32297-2]
CCDS53964.1 [P32297-3]
PIRiA37040
A53956
RefSeqiNP_000734.2, NM_000743.4 [P32297-2]
NP_001160166.1, NM_001166694.1 [P32297-3]
UniGeneiHs.89605

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZK4X-ray1.90A/B/C/D/E215-230[»]
5SYOX-ray2.00A/B/C/D/E215-230[»]
5TVCX-ray1.93A/B/C/D/E215-230[»]
ProteinModelPortaliP32297
SMRiP32297
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107558, 31 interactors
ComplexPortaliCPX-187 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2
CPX-210 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4
CPX-213 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4
CPX-2192 Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3
CPX-2193 Neuronal nicotinic acetylcholine receptor complex, alpha3-beta2
CPX-2200 Neuronal nicotinic acetylcholine receptor complex, alpha3-beta4
IntActiP32297, 3 interactors
STRINGi9606.ENSP00000315602

Chemistry databases

BindingDBiP32297
ChEMBLiCHEMBL3068
DrugBankiDB01156 Bupropion
DB09028 Cytisine
DB00514 Dextromethorphan
DB00898 Ethanol
DB00674 Galantamine
DB00848 Levamisole
DB01227 Levomethadyl Acetate
DB00184 Nicotine
DB01090 Pentolinium
DB01273 Varenicline
GuidetoPHARMACOLOGYi464

PTM databases

iPTMnetiP32297
PhosphoSitePlusiP32297

Polymorphism and mutation databases

BioMutaiCHRNA3
DMDMi254763435

Proteomic databases

PaxDbiP32297
PeptideAtlasiP32297
PRIDEiP32297
ProteomicsDBi54858
54859 [P32297-1]
54860 [P32297-3]

Protocols and materials databases

DNASUi1136
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326828; ENSP00000315602; ENSG00000080644 [P32297-2]
ENST00000348639; ENSP00000267951; ENSG00000080644 [P32297-3]
ENST00000559658; ENSP00000452896; ENSG00000080644 [P32297-2]
GeneIDi1136
KEGGihsa:1136
UCSCiuc002beb.4 human [P32297-2]

Organism-specific databases

CTDi1136
DisGeNETi1136
EuPathDBiHostDB:ENSG00000080644.15
GeneCardsiCHRNA3
H-InvDBiHIX0017542
HGNCiHGNC:1957 CHRNA3
HPAiHPA029430
MalaCardsiCHRNA3
MIMi118503 gene
612052 phenotype
neXtProtiNX_P32297
OpenTargetsiENSG00000080644
PharmGKBiPA113
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3645 Eukaryota
ENOG410XQGR LUCA
GeneTreeiENSGT00760000118930
HOVERGENiHBG003756
InParanoidiP32297
KOiK04805
OMAiQPLMARD
OrthoDBiEOG091G0R20
PhylomeDBiP32297
TreeFamiTF315605

Enzyme and pathway databases

ReactomeiR-HSA-629587 Highly sodium permeable acetylcholine nicotinic receptors
R-HSA-629594 Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597 Highly calcium permeable nicotinic acetylcholine receptors

Miscellaneous databases

ChiTaRSiCHRNA3 human
GeneWikiiCHRNA3
GenomeRNAii1136
PROiPR:P32297
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080644 Expressed in 125 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_CHRNA3
ExpressionAtlasiP32297 baseline and differential
GenevisibleiP32297 HS

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
IPR002394 Nicotinic_acetylcholine_rcpt
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR00254 NICOTINICR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACHA3_HUMAN
AccessioniPrimary (citable) accession number: P32297
Secondary accession number(s): Q15823
, Q4KMN8, Q86U77, Q96RH3, Q99553, Q9BQ93, Q9BRR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: July 28, 2009
Last modified: October 10, 2018
This is version 192 of the entry and version 4 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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