CHRM1

Protein identityUniProt · HPA

UniProt accession

P11229

Gene

CHRM1

Ensembl

ENSG00000168539

Chromosome

11

Canonical length

460 aa

Protein class

FDA approved drug targets, G-protein coupled receptors, Predicted membrane proteins

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 1 is involved in mediation of vagally-induced bronchoconstriction and in the acid secretion of the gastrointestinal tract. The gene encoding this receptor is localized to 11q13. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

460 residues, UniProt reviewed canonical sequence.

>P11229|CHRM1
     1  MNTSAPPAVS PNITVLAPGK GPWQVAFIGI TTGLLSLATV TGNLLVLISF KVNTELKTVN
    61  NYFLLSLACA DLIIGTFSMN LYTTYLLMGH WALGTLACDL WLALDYVASN ASVMNLLLIS
   121  FDRYFSVTRP LSYRAKRTPR RAALMIGLAW LVSFVLWAPA ILFWQYLVGE RTVLAGQCYI
   181  QFLSQPIITF GTAMAAFYLP VTVMCTLYWR IYRETENRAR ELAALQGSET PGKGGGSSSS
   241  SERSQPGAEG SPETPPGRCC RCCRAPRLLQ AYSWKEEEEE DEGSMESLTS SEGEEPGSEV
   301  VIKMPMVDPE AQAPTKQPPR SSPNTVKRPT KKGRDRAGKG QKPRGKEQLA KRKTFSLVKE
   361  KKAARTLSAI LLAFILTWTP YNIMVLVSTF CKDCVPETLW ELGYWLCYVN STINPMCYAL
   421  CNKAFRDTFR LLLLCRWDKR RWRKIPKRPG SVHRTPSRQC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CHRM1 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)

0.43

Highest tissue expression

48 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CHRM1.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 48 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• See cases
• CHRM1-related neurodevelopmental disorder

Disease | ImmuneIEDB

Conditions an epitope on CHRM1 was assayed in.

• Sjogren's syndrome B cell

ReferencesPubMed · IEDB

Publications for CHRM1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.21

gnomAD pLI

0.99

gnomAD missense Z

2.76

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
• chemical synaptic transmission
• cognition
• 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
• nervous system development
• neuromuscular synaptic transmission
• phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of intracellular protein transport
• positive regulation of monoatomic ion transport
• postsynaptic modulation of chemical synaptic transmission
• regulation of glial cell proliferation
• regulation of locomotion
• regulation of postsynaptic membrane potential
• saliva secretion
• signal transduction

Molecular functions

• G protein-coupled acetylcholine receptor activity
• phosphatidylinositol-4,5-bisphosphate phospholipase C activity

Cellular components

• axon terminus
• cholinergic synapse
• dendrite
• glutamatergic synapse
• membrane
• plasma membrane
• postsynaptic density membrane
• presynaptic membrane
• Schaffer collateral - CA1 synapse
• synapse

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Muscarinic acetylcholine receptor family
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Muscarinic acetylcholine receptor M1

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Synapse
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CHRM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GPRASP2
• TMEM147
• SLURP2