Protein:CHRNA1 |
Protein Summary |
 Gene summary |
| Gene name: CHRNA1 | ASpdb.0 ID: 1134 | Gene | Gene symbol | CHRNA1 | Gene ID | 1134 |
| Gene name | cholinergic receptor nicotinic alpha 1 subunit |
| Synonyms | ACHRA|ACHRD|CHRNA|CMS1A|CMS1B|CMS2A|FCCMS|SCCMS |
| Cytomap | 2q31.1 |
| Type of gene | protein-coding |
| Description | acetylcholine receptor subunit alphaacetylcholine receptor, nicotinic, alpha 1 (muscle)cholinergic receptor, nicotinic alpha 1cholinergic receptor, nicotinic, alpha 1 (muscle)cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle)muscle nicotin |
| Modification date | 20240411 |
| UniProtAcc | P02708 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CHRNA1 | GO:0005886 | plasma membrane | - |
| Gene | CHRNA1 | GO:0009986 | cell surface | 12928480 |
| Gene | CHRNA1 | GO:0031594 | neuromuscular junction | 9221765 |
| Gene | CHRNA1 | GO:0031594 | neuromuscular junction | 9221765 |
| Gene | CHRNA1 | GO:1904315 | transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | 9221765 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P02708-1 | P02708-1_4zjs_A.pdb | 4ZJS | X-ray | 2.23 | A | 106 | 126 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P02708 | CHRNA1 | P02708-1 | P02708-2 | 482 | 457 | 79 | 103 | Deletion | none | none | 78 | 78 |
| Multiple sequence alignment of our canonical and alternatively spliced CHRNA1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CHRNA1 |
| UniProt-id | ENSG | ENST | ENSP |
| P02708-1 | ENSG00000138435.16 | ENST00000261007.9 | ENSP00000261007.5 |
| P02708-2 | ENSG00000138435.16 | ENST00000348749.9 | ENSP00000261008.5 |
| UniProt-id | NM ID | NP ID |
| P02708-1 | NM_001039523.2 | NP_001034612.1 |
| P02708-2 | NM_000079.3 | NP_000070.1 |
| Amino acid sequences of our canonical and alternatively spliced CHRNA1 |
| accession_id | Protein sequence |
| P02708-1 | MEPWPLLLLFSLCSAGLVLGSEHETRLVAKLFKDYSSVVRPVEDHRQVVEVTVGLQLIQLINVDEVNQIVTTNVRLKQGDMVDLPRPSCV TLGVPLFSHLQNEQWVDYNLKWNPDDYGGVKKIHIPSEKIWRPDLVLYNNADGDFAIVKFTKVLLQYTGHITWTPPAIFKSYCEIIVTHF PFDEQNCSMKLGTWTYDGSVVAINPESDQPDLSNFMESGEWVIKESRGWKHSVTYSCCPDTPYLDITYHFVMQRLPLYFIVNVIIPCLLF SFLTGLVFYLPTDSGEKMTLSISVLLSLTVFLLVIVELIPSTSSAVPLIGKYMLFTMVFVIASIIITVIVINTHHRSPSTHVMPNWVRKV FIDTIPNIMFFSTMKRPSREKQDKKIFTEDIDISDISGKPGPPPMGFHSPLIKHPEVKSAIEGIKYIAETMKSDQESNNAAAEWKYVAMV |
| P02708-2 | MEPWPLLLLFSLCSAGLVLGSEHETRLVAKLFKDYSSVVRPVEDHRQVVEVTVGLQLIQLINVDEVNQIVTTNVRLKQQWVDYNLKWNPD DYGGVKKIHIPSEKIWRPDLVLYNNADGDFAIVKFTKVLLQYTGHITWTPPAIFKSYCEIIVTHFPFDEQNCSMKLGTWTYDGSVVAINP ESDQPDLSNFMESGEWVIKESRGWKHSVTYSCCPDTPYLDITYHFVMQRLPLYFIVNVIIPCLLFSFLTGLVFYLPTDSGEKMTLSISVL LSLTVFLLVIVELIPSTSSAVPLIGKYMLFTMVFVIASIIITVIVINTHHRSPSTHVMPNWVRKVFIDTIPNIMFFSTMKRPSREKQDKK IFTEDIDISDISGKPGPPPMGFHSPLIKHPEVKSAIEGIKYIAETMKSDQESNNAAAEWKYVAMVMDHILLGVFMLVCIIGTLAVFAGRL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CHRNA1 (go to UniProt):P02708 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P02708 | Topological domain | 21 | 232 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=79;End=103 |
Gene Isoform Structures and Expression Levels for CHRNA1 |
| Gene structures of our canonical and alternative spliced genes of CHRNA1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P02708-1 |
| 3D view using mol* of P02708-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P02708-1 |
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| pLDDT distribution across the protein length of P02708-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P02708-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P02708-1 | 0.858 | 41 | 0.884 | 191.051 | 0.559 | 0.705 | 1.034 | 1.998 | 0.431 | 4.636 | 1.171 | 362,375,377,380,381,384,439,442,443,445,446,449
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| P02708-2 | 0.968 | 103 | 1.001 | 273.714 | 0.624 | 0.63 | 0.891 | 0.395 | 0.974 | 0.406 | 0.683 | 333,337,338,351,352,353,354,355,357,358,359,360,36 1,362,363,407,410,411,414,417,418 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P02708-1_P02708-1_4zjs_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P02708-1_4zjs_A_P02708-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P02708-1_P02708-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P02708-1_vs_P02708-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P02708-1_vs_P02708-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CHRNA1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P02708 | CHRNA1 | DB08838 | Agmatine | experimental | antagonist |
| P02708 | CHRNA1 | DB00555 | Lamotrigine | approved, investigational | inhibitor |
| P02708 | CHRNA1 | DB00565 | Cisatracurium | approved, investigational | antagonist |
Related Diseases to CHRNA1 |
| Previous studies relating to the alternative splicing of CHRNA1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CHRNA1 | 18806275 | hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. | In humans and great apes, CHRNA1 encoding the muscle nicotinic acetylcholine receptor alpha subunit carries an inframe exon P3A, the inclusion of which yields a nonfunctional alpha subunit. In muscle, the P3A(-) and P3A(+) transcripts are generated in a 1:1 ratio but the functional significance and regulation of the alternative splicing remain elusive. An intronic mutation (IVS3-8G>A), identified in a patient with congenital myasthenic syndrome, disrupts an intronic splicing silencer (ISS) and results in exclusive inclusion of the downstream P3A exon. We found that the ISS-binding splicing trans-factor was heterogeneous nuclear ribonucleoprotein (hnRNP) H and the mutation attenuated the affinity of hnRNP for the ISS approximately 100-fold. We next showed that direct placement of hnRNP H to the 3' end of intron 3 silences, and siRNA-mediated downregulation of hnRNP H enhances recognition of exon P3A. Analysis of the human genome suggested that the hnRNPH-binding UGGG motif is overrepresented close to the 3' ends of introns. Pursuing this clue, we showed that alternative exons of GRIP1, FAS, VPS13C and NRCAM are downregulated by hnRNP H. Our findings imply that the presence of the hnRNP H-binding motif close to the 3' end of an intron is an essential but underestimated splicing regulator of the downstream exon. | D020294 | Myasthenic Syndromes, Congenital |
| CHRNA1 | 25888793 | Antisense oligonucleotide-mediated exon skipping of CHRNA1 pre-mRNA as potential therapy for Congenital Myasthenic Syndromes. | CHRNA1 encodes the α subunit of nicotinic acetylcholine receptors (nAChRs) and is expressed at the neuromuscular junction. Moreover, it is one of the causative genes of Congenital Myasthenic Syndromes (CMS). CHRNA1 undergoes alternative splicing to produce two splice variants: P3A(-), without exon P3A, and P3A(+), with the exon P3A. Only P3A(-) forms functional nAChR. Aberrant alternative splicing caused by intronic or exonic point mutations in patients leads to an extraordinary increase in P3A(+) and a concomitant decrease in P3A(-). Consequently this resulted in a shortage of functional receptors. Aiming to restore the imbalance between the two splice products, antisense oligonucleotides (AONs) were employed to induce exon P3A skipping. Three AON sequences were designed to sterically block the putative binding sequences for splicing factors necessary for exon recognition. Herein, we show that AON complementary to the 5' splice site of the exon was the most effective at exon skipping of the minigene with causative mutations, as well as endogenous wild-type CHRNA1. We conclude that single administration of the AON against the 5' splice site is a promising therapeutic approach for patients based on the dose-dependent effect of the AON and the additive effect of combined AONs. This conclusion is favorable to patients with inherited diseases of uncertain etiology that arise from aberrant splicing leading to a subsequent loss of functional translation products because our findings encourage the option of AON treatment as a therapeutic for these prospectively identified diseases. | D020294 | Myasthenic Syndromes, Congenital |
Clinically important variants in CHRNA1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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