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Protein

Neuronal acetylcholine receptor subunit alpha-4

Gene

CHRNA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 permeable to sodium ions.1 Publication

GO - Molecular functioni

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

GO - Biological processi

  • acetylcholine receptor signaling pathway Source: Ensembl
  • action potential Source: UniProtKB
  • B cell activation Source: UniProtKB
  • behavioral response to nicotine Source: UniProtKB
  • calcium ion transport Source: UniProtKB
  • chemical synaptic transmission Source: UniProtKB
  • cognition Source: UniProtKB
  • DNA repair Source: UniProtKB
  • exploration behavior Source: Ensembl
  • inhibitory postsynaptic potential Source: UniProtKB
  • ion transport Source: UniProtKB
  • locomotory behavior Source: Ensembl
  • membrane depolarization Source: UniProtKB
  • neurological system process Source: UniProtKB
  • neuromuscular synaptic transmission Source: GO_Central
  • regulation of dopamine secretion Source: UniProtKB
  • regulation of membrane potential Source: UniProtKB
  • respiratory gaseous exchange Source: Ensembl
  • response to hypoxia Source: UniProtKB
  • response to nicotine Source: UniProtKB
  • response to oxidative stress Source: UniProtKB
  • sensory perception of pain Source: UniProtKB
  • signal transduction Source: UniProtKB
  • synaptic transmission, cholinergic Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101204-MONOMER.
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.

Protein family/group databases

TCDBi1.A.9.1.6. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal acetylcholine receptor subunit alpha-4
Gene namesi
Name:CHRNA4
Synonyms:NACRA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:1958. CHRNA4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 242ExtracellularSequence analysisAdd BLAST214
Transmembranei243 – 267HelicalSequence analysisAdd BLAST25
Transmembranei275 – 293HelicalSequence analysisAdd BLAST19
Transmembranei309 – 330HelicalSequence analysisAdd BLAST22
Topological domaini331 – 600CytoplasmicSequence analysisAdd BLAST270
Transmembranei601 – 619HelicalSequence analysisAdd BLAST19

GO - Cellular componenti

  • acetylcholine-gated channel complex Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • dendrite Source: UniProtKB
  • external side of plasma membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Epilepsy, nocturnal frontal lobe, 1 (ENFL1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
See also OMIM:600513
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000295280S → F in ENFL1. 1 PublicationCorresponds to variant rs121909580dbSNPEnsembl.1
Natural variantiVAR_017531280S → L in ENFL1. 2 Publications1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi1137.
MalaCardsiCHRNA4.
MIMi600513. phenotype.
OpenTargetsiENSG00000101204.
Orphaneti98784. Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKBiPA26490.

Chemistry databases

ChEMBLiCHEMBL1882.
DrugBankiDB01351. Amobarbital.
DB01352. Aprobarbital.
DB00237. Butabarbital.
DB00241. Butalbital.
DB01353. Butethal.
DB09028. Cytisine.
DB00514. Dextromethorphan.
DB00898. Ethanol.
DB00674. Galantamine.
DB01354. Heptabarbital.
DB01355. Hexobarbital.
DB00849. Methylphenobarbital.
DB00184. Nicotine.
DB00312. Pentobarbital.
DB01174. Phenobarbital.
DB00794. Primidone.
DB00418. Secobarbital.
DB00306. Talbutal.
DB00599. Thiopental.
DB01273. Varenicline.
GuidetoPHARMACOLOGYi465.

Polymorphism and mutation databases

BioMutaiCHRNA4.
DMDMi1351848.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000000035129 – 627Neuronal acetylcholine receptor subunit alpha-4Add BLAST599

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi57N-linked (GlcNAc...)Sequence analysis1
Glycosylationi107N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi161 ↔ 175By similarity
Glycosylationi174N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi225 ↔ 226Associated with receptor activationBy similarity
Lipidationi271S-palmitoyl cysteineBy similarity1
Modified residuei424PhosphoserineBy similarity1
Modified residuei538PhosphoserineBy similarity1
Modified residuei541PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP43681.
PeptideAtlasiP43681.
PRIDEiP43681.

PTM databases

iPTMnetiP43681.
PhosphoSitePlusiP43681.
SwissPalmiP43681.

Expressioni

Gene expression databases

BgeeiENSG00000101204.
CleanExiHS_CHRNA4.
ExpressionAtlasiP43681. baseline and differential.
GenevisibleiP43681. HS.

Organism-specific databases

HPAiCAB034064.

Interactioni

Subunit structurei

Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-4 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers. Interacts with RIC3; which is required for proper folding and assembly.2 Publications

Protein-protein interaction databases

BioGridi107559. 4 interactors.
IntActiP43681. 2 interactors.
MINTiMINT-3015931.
STRINGi9606.ENSP00000359285.

Chemistry databases

BindingDBiP43681.

Structurei

Secondary structure

1627
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi244 – 266Combined sources23
Helixi273 – 295Combined sources23
Beta strandi300 – 302Combined sources3
Helixi307 – 329Combined sources23
Helixi598 – 618Combined sources21
Turni622 – 624Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GVTmodel-A/C38-241[»]
2LLYNMR-A240-339[»]
A598-626[»]
5KXIX-ray3.94A/D27-364[»]
A/D586-627[»]
ProteinModelPortaliP43681.
SMRiP43681.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3645. Eukaryota.
ENOG410XQGR. LUCA.
GeneTreeiENSGT00760000118930.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiP43681.
KOiK04806.
OMAiHMSSPGE.
OrthoDBiEOG091G0R20.
PhylomeDBiP43681.
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. 3 hits.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 2 hits.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P43681-1) [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
MELGGPGAPR LLPPLLLLLG TGLLRASSHV ETRAHAEERL LKKLFSGYNK
60 70 80 90 100
WSRPVANISD VVLVRFGLSI AQLIDVDEKN QMMTTNVWVK QEWHDYKLRW
110 120 130 140 150
DPADYENVTS IRIPSELIWR PDIVLYNNAD GDFAVTHLTK AHLFHDGRVQ
160 170 180 190 200
WTPPAIYKSS CSIDVTFFPF DQQNCTMKFG SWTYDKAKID LVNMHSRVDQ
210 220 230 240 250
LDFWESGEWV IVDAVGTYNT RKYECCAEIY PDITYAFVIR RLPLFYTINL
260 270 280 290 300
IIPCLLISCL TVLVFYLPSE CGEKITLCIS VLLSLTVFLL LITEIIPSTS
310 320 330 340 350
LVIPLIGEYL LFTMIFVTLS IVITVFVLNV HHRSPRTHTM PTWVRRVFLD
360 370 380 390 400
IVPRLLLMKR PSVVKDNCRR LIESMHKMAS APRFWPEPEG EPPATSGTQS
410 420 430 440 450
LHPPSPSFCV PLDVPAEPGP SCKSPSDQLP PQQPLEAEKA SPHPSPGPCR
460 470 480 490 500
PPHGTQAPGL AKARSLSVQH MSSPGEAVEG GVRCRSRSIQ YCVPRDDAAP
510 520 530 540 550
EADGQAAGAL ASRNTHSAEL PPPDQPSPCK CTCKKEPSSV SPSATVKTRS
560 570 580 590 600
TKAPPPHLPL SPALTRAVEG VQYIADHLKA EDTDFSVKED WKYVAMVIDR
610 620
IFLWMFIIVC LLGTVGLFLP PWLAGMI
Length:627
Mass (Da):69,957
Last modified:February 1, 1996 - v2
Checksum:iB3A0C0151E5A2AA8
GO
Isoform 2 (identifier: P43681-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: MELGGPGAPR...YNKWSRPVAN → MRMSPPSASP...VWTAGCPGEG
     58-128: Missing.

Note: No experimental confirmation available.
Show »
Length:556
Mass (Da):60,994
Checksum:iCE5902DBC1231CA3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4G → E in AAH96290 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000295280S → F in ENFL1. 1 PublicationCorresponds to variant rs121909580dbSNPEnsembl.1
Natural variantiVAR_017531280S → L in ENFL1. 2 Publications1
Natural variantiVAR_023402387E → G.1 PublicationCorresponds to variant rs45604738dbSNPEnsembl.1
Natural variantiVAR_023403517S → L.1 PublicationCorresponds to variant rs45622132dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0542751 – 57MELGG…RPVAN → MRMSPPSASPPSSSGGRTSS STTTAGEPFWAGVLFAIRPH PGLSGRIVWTAGCPGEG in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_05427658 – 128Missing in isoform 2. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35901 mRNA. Translation: AAA64743.1.
X89741
, X89742, X89743, X89744, X89745, X89746 Genomic DNA. Translation: CAA61893.1.
U62433 mRNA. Translation: AAB40111.1.
Y08421 mRNA. Translation: CAA69698.1.
DQ093071 Genomic DNA. Translation: AAY88737.1.
AL121827 Genomic DNA. No translation available.
BC096290 mRNA. Translation: AAH96290.1.
BC096291 mRNA. Translation: AAH96291.1.
X87629 mRNA. Translation: CAA60959.1.
CCDSiCCDS13517.1. [P43681-1]
PIRiJC4021.
RefSeqiNP_000735.1. NM_000744.6. [P43681-1]
NP_001243502.1. NM_001256573.1.
XP_011526826.1. XM_011528524.1. [P43681-2]
UniGeneiHs.10734.

Genome annotation databases

EnsembliENST00000370263; ENSP00000359285; ENSG00000101204. [P43681-1]
ENST00000615287; ENSP00000483388; ENSG00000101204. [P43681-2]
GeneIDi1137.
KEGGihsa:1137.
UCSCiuc002yes.4. human. [P43681-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35901 mRNA. Translation: AAA64743.1.
X89741
, X89742, X89743, X89744, X89745, X89746 Genomic DNA. Translation: CAA61893.1.
U62433 mRNA. Translation: AAB40111.1.
Y08421 mRNA. Translation: CAA69698.1.
DQ093071 Genomic DNA. Translation: AAY88737.1.
AL121827 Genomic DNA. No translation available.
BC096290 mRNA. Translation: AAH96290.1.
BC096291 mRNA. Translation: AAH96291.1.
X87629 mRNA. Translation: CAA60959.1.
CCDSiCCDS13517.1. [P43681-1]
PIRiJC4021.
RefSeqiNP_000735.1. NM_000744.6. [P43681-1]
NP_001243502.1. NM_001256573.1.
XP_011526826.1. XM_011528524.1. [P43681-2]
UniGeneiHs.10734.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GVTmodel-A/C38-241[»]
2LLYNMR-A240-339[»]
A598-626[»]
5KXIX-ray3.94A/D27-364[»]
A/D586-627[»]
ProteinModelPortaliP43681.
SMRiP43681.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107559. 4 interactors.
IntActiP43681. 2 interactors.
MINTiMINT-3015931.
STRINGi9606.ENSP00000359285.

Chemistry databases

BindingDBiP43681.
ChEMBLiCHEMBL1882.
DrugBankiDB01351. Amobarbital.
DB01352. Aprobarbital.
DB00237. Butabarbital.
DB00241. Butalbital.
DB01353. Butethal.
DB09028. Cytisine.
DB00514. Dextromethorphan.
DB00898. Ethanol.
DB00674. Galantamine.
DB01354. Heptabarbital.
DB01355. Hexobarbital.
DB00849. Methylphenobarbital.
DB00184. Nicotine.
DB00312. Pentobarbital.
DB01174. Phenobarbital.
DB00794. Primidone.
DB00418. Secobarbital.
DB00306. Talbutal.
DB00599. Thiopental.
DB01273. Varenicline.
GuidetoPHARMACOLOGYi465.

Protein family/group databases

TCDBi1.A.9.1.6. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

iPTMnetiP43681.
PhosphoSitePlusiP43681.
SwissPalmiP43681.

Polymorphism and mutation databases

BioMutaiCHRNA4.
DMDMi1351848.

Proteomic databases

PaxDbiP43681.
PeptideAtlasiP43681.
PRIDEiP43681.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370263; ENSP00000359285; ENSG00000101204. [P43681-1]
ENST00000615287; ENSP00000483388; ENSG00000101204. [P43681-2]
GeneIDi1137.
KEGGihsa:1137.
UCSCiuc002yes.4. human. [P43681-1]

Organism-specific databases

CTDi1137.
DisGeNETi1137.
GeneCardsiCHRNA4.
GeneReviewsiCHRNA4.
HGNCiHGNC:1958. CHRNA4.
HPAiCAB034064.
MalaCardsiCHRNA4.
MIMi118504. gene.
600513. phenotype.
neXtProtiNX_P43681.
OpenTargetsiENSG00000101204.
Orphaneti98784. Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKBiPA26490.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3645. Eukaryota.
ENOG410XQGR. LUCA.
GeneTreeiENSGT00760000118930.
HOGENOMiHOG000006756.
HOVERGENiHBG003756.
InParanoidiP43681.
KOiK04806.
OMAiHMSSPGE.
OrthoDBiEOG091G0R20.
PhylomeDBiP43681.
TreeFamiTF315605.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101204-MONOMER.
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

ChiTaRSiCHRNA4. human.
GeneWikiiCHRNA4.
GenomeRNAii1137.
PROiP43681.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101204.
CleanExiHS_CHRNA4.
ExpressionAtlasiP43681. baseline and differential.
GenevisibleiP43681. 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. 3 hits.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR00254. NICOTINICR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 2 hits.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACHA4_HUMAN
AccessioniPrimary (citable) accession number: P43681
Secondary accession number(s): Q4JGR7, Q4VAQ5, Q4VAQ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 177 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.