Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CHRM3 contributors: mct/ - updated : 13-05-2020
HGNC name cholinergic receptor, muscarinic 3
HGNC id 1952
Corresponding disease
DUP1QD chromosome 1q distal duplication
PBLS prune-belly-like syndrome
Location 1q43      Physical location : 239.792.372 - 240.072.715
Synonym name
  • m3 muscarinic receptor
  • muscarinic acetylcholine receptor M3
  • Synonym symbol(s) EGBRS, HM3, M3R, M3, mAChR
    DNA
    TYPE functioning gene
    STRUCTURE 528.89 kb     5 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 8793 - 590 - 2011 21056967
    8 - 9408 - 590 - 2011 21056967
    7 - 9183 - 590 - 2011 21056967
    7 - 9179 - 590 - 2011 21056967
    7 - 9220 - 590 - 2011 21056967
    6 - 9120 - 590 - 2011 21056967
    6 - 9080 - 590 - 2011 21056967
    7 - 9184 - 590 - 2011 21056967
    6 - 9121 - 590 - 2011 21056967
    5 - 9017 - 590 - 2011 21056967
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiens
    Endocrineadrenal gland   highly
    Lymphoid/Immunethymus   highly
    Respiratoryrespiratory tractlarynx  highly
    Urinarybladder   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • present in developing renal epithelia and bladder muscle, and not only, but also in the urogenital sinus and fetal urethral epithelia
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor
  • HOMOLOGY
    Homologene
    FAMILY
  • G protein coupled receptor superfamily
  • k1 cholinergic receptor
  • CATEGORY receptor , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • controling smooth muscle contraction and by its stimulation causes secretion of glandular tissue
  • mediating various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins
  • having a role in stimulating insulin secretion
  • major receptor involved in mediating urinary bladder contraction upon micturition
  • critical role for central CHRM3 in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells
  • role in mediating enteric cholinergic neurotransmission
  • regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner
  • regulates many fundamental physiological functions
  • promotes insulin release via receptor phosphorylation/arrestin-dependent activation of protein kinase D1
  • may have a role beyond its known contribution to detrusor contractions
  • play important roles in the pathogenesis of myopia and in the arrested progression of myopia by atropine
  • major role of CHRM3 mediating the human gallbladder contraction through voltage-gated Ca(2+) channels and Rho kinase
  • preserves the endothelial barrier function through a mechanism potentially maintaining PTPN1 activity, keeping the adherens junction proteins (AJPs) dephosphorylation
  • is an acetylcholine receptor that regulates the activity of numerous fundamental central and peripheral nervous system functions
  • expression plays an important role in early progression and invasion of colon neoplasia but is less important once tumors have spread
  • in pancreatic beta cells, muscarinic cholinergic receptor M3 (CHRM3) stimulates glucose-induced secretion of insulin
  • CHRM1 and CHRM3, are essential for rapid eye movement (REM) sleep
  • M3 muscarinic acetylcholine receptor that is located on the surface of smooth muscle cells of the detrusor, the muscle that effects urinary voiding
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TMEM147 is a CHRM3-associated protein (represents a potent negative regulator of M3R function, most likely by interacting with M3Rs in an intracellular compartment (ER)
  • intracellular functional link between CHRM3 and TRPM8 channel via KAT5, suggesting a novel physiological mechanism of arachidonate-mediated regulation of TRPM8 channel activity through muscarinic receptors
  • odorant receptors (ORs) and CHRM3 physically interacted, and CHRM3 increased the potency and efficacy of odorant-elicited responses of several ORs
  • GJA4, GJA5, contribute to the propagation and amplification of the Ca(2+) signaling triggered by Acetylcholine (ACh) in endothelial cells expressing CHRM3
  • interplay of CHRM3 and beta-catenin signaling is important for intestinal mucosal differentiation and neoplasia
  • direct interaction between CHRM3 and PLCB3
  • CHRM3 facilitates interaction of the CDH5-based adherens junctional complex and the actin-based cytoskeleton by maintaining RAC1 activity, which regulates the interaction between IQGAP1/RAC1 and IQGAP1/CTNNB1, and may contribute to endothelial barrier function under physiological conditions
  • physically interact with odorant receptors (ORs) to promote odour-induced responses in a heterologous expression system
  • activation of CHRM3 inhibits the recruitment of ARRB2 to odorant receptors (ORs), resulting in a potentiation of odour-induced responses in olfactory sensory neurons (OSNs)
  • NOSTRIN is crucial for the localization and function of the CHRM3 and NO production
  • CHRM3 modulate EIF4B phosphorylation via the ERK1/2 and PKC signaling pathways in colon cancer cells
  • CHRM3-induced activation of MAPK14 might contribute to the maintenance of epithelial barrier function through down-regulation of TNF signalling and activation of EGFR
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PBLS , DUP1QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colon cancer
    constitutional       gain of function
    delayed cardiac aging by inhibiting the CASP1/IL1B signaling pathway
    tumoral     --over  
    in colon cancer
    tumoral     --over  
    in gastric cancer (GC) tissues and was correlated with the cancer stage and with lymph node metastasis
    Susceptibility
  • to type 2 diabetes
  • to elevated blood pressure (BP)
  • Variant & Polymorphism other
  • polymorphisms increasing the risk of early-onset type 2 diabetes
  • a CHRM3-coding variation increased M3R signaling, correlating with higher BP
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    respiratory  
    may be important therapeutic target for obstructive airway diseases, as it regulates the effects of the epithelial-derived chemokines on airway smooth muscle (ASM) cell migration (PMID: 26956674)
    ANIMAL & CELL MODELS
  • megacystis is present in younger Chrm3 mutant mice, and the hypocontractile bladder phenotype is very similar to humans with CHRM3 mutations
  • the loss of NOSTRIN in mice leads to endothelial dysfunction, increased blood pressure, and diastolic heart failure
  • Chrm1 and Chrm3 double knockout chronically diminishes REM sleep to an almost undetectable level