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FLASH GENE

Symbol

CX3CR1

contributors: shn/npt/pgu - updated : 28-09-2020

HGNC name	chemokine (C-X3-C motif) receptor 1
HGNC id	2558

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	3p22.2      Physical location : 39.304.985 - 39.323.226
Synonym name	G protein-coupled receptor 13
	fractalkine receptor CX3CR1
	chemokine (C-C) receptor-like 1
	chemokine (C-X3-C) receptor 1
	chemokine, CX3C motif, receptor 1
Synonym symbol(s)	CMKBRL1, CHEMR1, CCRL1, GPR13, CMKDR1, V28, C3X1, GPRV28,

DNA

TYPE	functioning gene
STRUCTURE	18.24 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D3S3605 - D3S3593 - CX3CR1 - D3S3527 - D3S3522 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001171174 2 splicing 3160 NP_001164645 - 387 - 2003 14607932 NM_001171172 2 splicing 3224 NP_001164643 - 355 - 2003 14607932 NM_001171171 2 splicing 3264 NP_001164642 - 355 - 2003 14607932 NM_001337 2 splicing 3108 NP_001328 - 355 - 2003 14607932

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 Endocrine pancreas         Homo sapiens Nervous brain diencephalon hypothalamus   highly Visual eye retina     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Endocrine islet cell (alpha,beta...) Homo sapiens Lymphoid/Immune dendritic cell Homo sapiens Lymphoid/Immune macrophage Homo sapiens Lymphoid/Immune T cell Homo sapiens Nervous glia Homo sapiens Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor, carrying the chemokine domain on top of an extended mucin-like stalk
	a binding site mapping to a region of greatest flexibility and structural variability

HOMOLOGY

interspecies	ortholog to CX3CR1, Pan troglodytes
	ortholog to Cx3cr1, Rattus norvegicus
	ortholog to Cx3cl1, Mus musculus

Homologene

FAMILY	G-protein coupled receptor superfamily
	CX3C family

CATEGORY

regulatory , signaling , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
text	multi-pass membrane protein

basic FUNCTION	receptor for fractalkine and a coreceptor for HIV-1
	chemokine (C-X3-C) receptor 1, mediating leukocyte migration and adhesion
	involved in the pathogenesis of atherosclerotic disease
	mediates both leukocyte migration and adhesion
	neuronal CX3CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia
	control the clearance of entero-invasive pathogens by dendritic cells and may regulate immunological tolerance and inflammation
	role in potentiating the rate of retinal microglial process dynamism and cellular migration
	provides a survival signal to TH2 cells that is required for airway disease
	CX3CR1 and CX3CL1 are required for the survival of both TH1 and TH2 cells in inflamed airways
	key microglial pathway in protecting against Alzheimer disease-related cognitive deficits that are associated with aberrant microglial activation and elevated inflammatory cytokine
	both CCR2 and CX3CR1 regulate arteriole growth, but only bone marrow-derived cell-expressed CX3CR1 impacts small venule growth
	important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization
	fractalkine-receptor/CX3CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties
	CX3CL1 and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke
	neuronal CX3CR1 mediates neuronal apoptotic cell death in ischemia
	CX3CL1/CX3CR1 communication system has anti-inflammatory and neuroprotective effects and plays an important role in maintaining autophagy activity
	fractalkine/CX3CR1 axis regulates microglial activation and function, neuronal survival and synaptic function by controlling the release of inflammatory cytokines and synaptic plasticity in the course of the neurological disease
	appears to play a mechanistic role in mediating viral infection of pediatric airway epithelial cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation , cellular trafficking transport

PATHWAY

metabolism

signaling

signal transduction

a component

CX3CL1-CX3CR1 axis is a highly adhesive pair involved in the firm adhesion of monocytes or lymphocytes on activated endothelium

INTERACTION

DNA

RNA

small molecule

protein	activating the protein kinase Akt and nuclear translocation of NFKB
	chemokine (C-X3-C motif) ligand 1, CX3CL1
	CCL26 is yet a functional ligand for CX3CR1, the receptor for fractalkine/CX3CL1, which is expressed by CD16(+) NK cells, cytotoxic effector CD8(+) T cells, and CD14(low)CD16(high) monocytes
	CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells
	CX3CL1/CX3CR1 contributes positively to neuron protective as well as detrimental role in the course of the disease
	CX3CR1 is a novel target for the clearance of extracellular MAPT
	CX3CR1/CX3CL1 axis plays a key role in the phagocytosis of MAPT by microglia and that it is affected as Alzheimer disease progresses

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in airway smooth muscle, lung endothelium and epithelium upon allergen challenge, in people with asthma constitutional       loss of function fractalkine signaling (CX3CL1/ CX3CR1) is deficient in the vulnerable regions of Alzheimer brains

Susceptibility

to coronary artery disease to brain infarction to age-related macular degeneration to autism spectrum disorder to HIV-1 infection and rapid progression to AIDS

Variant & Polymorphism other	rapid progression of AIDS in HIV+ (Omim: 609423)
	individuals homozygous for CXRCR1 (haplotype I249M280)
	polymorphisms modulating its adhesive and signaling functions, associated with reduced risk of atherosclerotic cardiovascular disease(I249M)
	I249 and M280 alleles were associated with an increased risk of brain infarction
	prevalence of T280M polymorphism associated with retinal vasculitis in UK patients
	polymorphisms increasing the risk of age-related macular degeneration

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed allergy asthm   CX3CR1 and CX3CL1 may represent attractive therapeutic targets in asthma cancer metastases   CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as cancer bone metastasis osteoarticular bone ostéoporosis CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis, osteoporosis neurology neurodegenerative   CX3CL1/CX3CR1 communication system is a therapeutic target for amyotrophic lateral sclerosis (ALS)patients neurosensorial visual degenerative CX3CL1-CX3CR1 signaling is a molecular mechanism capable of modulating microglial-mediated degeneration and represents a potential molecular target in therapeutic approaches to RP

ANIMAL & CELL MODELS

	CX3CR1(-/-) mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation
	Retinal microglial density, distribution, cellular morphology, and overall retinal tissue anatomy were not altered in young CX3CR1(-/-) mice
	deleting CX3CR1 in hAPP mice increased expression of inflammatory factors, such as TNF and IL6, and exacerbated plaque-independent neuronal dysfunction and cognitive deficits
	in Cx3cr1-deficient (CX3CR1(GFP/GFP) ) rd10 mice microglial infiltration into the photoreceptor layer was significantly augmented and associated with accelerated photoreceptor apoptosis and atrophy