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FLASH GENE

Symbol

CHRM3

contributors: mct/ - updated : 13-05-2020

HGNC name	cholinergic receptor, muscarinic 3
HGNC id	1952

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000740 5 - 8793 NP_000731 - 590 - 2011 21056967 NM_001347716 8 - 9408 NP_001334645 - 590 - 2011 21056967 NM_001375982 7 - 9183 NP_001362911 - 590 - 2011 21056967 NM_001375978 7 - 9179 NP_001362907 - 590 - 2011 21056967 NM_001375983 7 - 9220 NP_001362912 - 590 - 2011 21056967 NM_001375979 6 - 9120 NP_001362908 - 590 - 2011 21056967 NM_001375981 6 - 9080 NP_001362910 - 590 - 2011 21056967 NM_001375984 7 - 9184 NP_001362913 - 590 - 2011 21056967 NM_001375985 6 - 9121 NP_001362914 - 590 - 2011 21056967 NM_001375980 5 - 9017 NP_001362909 - 590 - 2011 21056967

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Homo sapiens Endocrine adrenal gland       highly Lymphoid/Immune thymus       highly Respiratory respiratory tract larynx     highly Urinary bladder       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed 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