CHRM3
Muscarinic acetylcholine receptor M3
Also known as: ACM3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P20309
- Gene
- CHRM3
- Ensembl
- ENSG00000133019
- Chromosome
- 1
- Canonical length
- 590 aa
- Protein class
- Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins
- Subcellular location
- Plasma membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 3 controls smooth muscle contraction and its stimulation causes secretion of glandular tissue. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]
Canonical amino-acid sequenceUniProt
590 residues, UniProt reviewed canonical sequence.
>P20309|CHRM3
1 MTLHNNSTTS PLFPNISSSW IHSPSDAGLP PGTVTHFGSY NVSRAAGNFS SPDGTTDDPL
61 GGHTVWQVVF IAFLTGILAL VTIIGNILVI VSFKVNKQLK TVNNYFLLSL ACADLIIGVI
121 SMNLFTTYII MNRWALGNLA CDLWLAIDYV ASNASVMNLL VISFDRYFSI TRPLTYRAKR
181 TTKRAGVMIG LAWVISFVLW APAILFWQYF VGKRTVPPGE CFIQFLSEPT ITFGTAIAAF
241 YMPVTIMTIL YWRIYKETEK RTKELAGLQA SGTEAETENF VHPTGSSRSC SSYELQQQSM
301 KRSNRRKYGR CHFWFTTKSW KPSSEQMDQD HSSSDSWNNN DAAASLENSA SSDEEDIGSE
361 TRAIYSIVLK LPGHSTILNS TKLPSSDNLQ VPEEELGMVD LERKADKLQA QKSVDDGGSF
421 PKSFSKLPIQ LESAVDTAKT SDVNSSVGKS TATLPLSFKE ATLAKRFALK TRSQITKRKR
481 MSLVKEKKAA QTLSAILLAF IITWTPYNIM VLVNTFCDSC IPKTFWNLGY WLCYINSTVN
541 PVCYALCNKT FRTTFKMLLL CQCDKKKRRK QQYQQRQSVI FHKRAPEQALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CHRM3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 7
- Mean surface accessibility (rSASA)
- 0.47
- Highest tissue expression
- 17 nTPM
Expression across tissuesHPA
Tissue
- salivary gland: 17 nTPM
- pancreas: 10 nTPM
- cerebral cortex: 9.4 nTPM
- urinary bladder: 7.2 nTPM
- esophagus: 7 nTPM
- colon: 6.4 nTPM
Single-cell type
- salivary acinar cells: 2,061 nCPM
- salivary myoepithelial cells: 1,306 nCPM
- pancreatic acinar cells: 984 nCPM
- hematopoietic stem cells: 699 nCPM
- mucous neck cells: 597 nCPM
- lacrimal acinar cells: 585 nCPM
Immune cell
- naive CD4 T-cell: 0.3 nTPM
- intermediate monocyte: 0.2 nTPM
- MAIT T-cell: 0.1 nTPM
- naive CD8 T-cell: 0.1 nTPM
- non-classical monocyte: 0.1 nTPM
- basophil: 0 nTPM
Brain region
- cerebral cortex: 62 nTPM
- white matter: 43 nTPM
- basal ganglia: 41 nTPM
- thalamus: 40 nTPM
- amygdala: 34 nTPM
- pons: 23 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CHRM3.
Disease | AllUniProt
Conditions CHRM3 is implicated in, by any mechanism.
- Prune belly syndrome (PBS) MIM:100100
Disease | GeneticClinVar
3 pathogenic / likely-pathogenic of 153 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Disease | ImmuneIEDB
Conditions an epitope on CHRM3 was assayed in.
- Sjogren's syndrome B cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.25
- gnomAD pLI
- 0.99
- gnomAD missense Z
- 1.96
- DepMap mean gene effect
- 0.1
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- acetylcholine receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
- calcium-mediated signaling
- chemical synaptic transmission
- G protein-coupled acetylcholine receptor signaling pathway
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- ligand-gated ion channel signaling pathway
- nervous system development
- phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway
- positive regulation of insulin secretion
- positive regulation of smooth muscle contraction
- protein modification process
- regulation of smooth muscle contraction
- saliva secretion
- signal transduction
- smooth muscle contraction
Molecular functions
- acetylcholine binding
- G protein-coupled acetylcholine receptor activity
- phosphatidylinositol-4,5-bisphosphate phospholipase C activity
- signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CHRM3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CHRM3 as an antibody target. Whether an autoantibody or antibody against CHRM3 could matter depends on whether native CHRM3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CHRM3 is annotated at the cell surface, where native CHRM3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CHRM3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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