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FLASH GENE
Symbol CHRM3 contributors: mct/ - updated : 13-05-2020
HGNC name cholinergic receptor, muscarinic 3
HGNC id 1952
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