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FLASH GENE

Symbol

CCR5

contributors: mct - updated : 29-05-2020

HGNC name	chemokine (C-C motif) receptor 5
HGNC id	1606

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	3p21.31      Physical location : 46.411.632 - 46.417.690
Synonym name	small inducible cytokine (CCL3, CCL4, CCL5) common receptor
	CD195 antigen
	HIV-1 fusion coreceptor
	chemokine receptor CCR5
	chemokine recptor CCR5 Delta32
Synonym symbol(s)	CMKBR5, CKR-5, CC-CKR-5, CKR5, CD195, FLJ78003, IDDM22

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	member of a chemokine receptor gene cluster
STRUCTURE	6.06 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	differing in their 5'utr by alternative splicing of exon 2 and exon 3

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000579 3 initiation site 3686 NP_000570 40.5 352 lymphocytes - 8663314 NM_001100168 3 initiation site 3451 NP_001093638 - 352 - - 8663314 CCR5-delta32 - - - - - - 2015 25918237 32 bp deletion in the CCR5 gene CCR5-delta32 patients are at higher risk than the normal population of a fatal outcome in influenza infection

EXPRESSION

Type	restricted

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 Lymphoid/Immune lymph node           thymus         Urinary kidney         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid         Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens Lymphoid/Immune macrophage Homo sapiens Lymphoid/Immune T cell Homo sapiens

cell lineage
cell lines	promyeloblastic cell line
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

five transmembrane domains (TM3-TM6) sufficient for the function

HOMOLOGY

Homologene

FAMILY

G-protein coupled receptor 1 family

CATEGORY

receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	mediating macrophage-tropic strains of HIV-1 entry in CD4+ T lymphocytes
	during human T cell activation by antigen-presenting cells, recruited into the immunological synapse, where they deliver costimulatory signals
	important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction
	CXCR4 and the related CCR5 serve as co-receptors for HIV-1 viral particles, facilitating their entry into cells
	is a novel link between obesity, adipose tissue inflammation, and insulin resistance
	acts as the principal coreceptor during HIV-1 transmission and early stages of infection
	is the major coreceptor for human immunodeficiency virus (HIV)
	CCR5 is a host factor required for Dengue virus (DENV-2) replication in human macrophages
	plays an important role in neuroplasticity, learning and memory, and CCR5 has a role in the cognitive deficits caused by HIV
	critical role for CCR5 not only in the recruitment but also in the activation of myeloid-derived suppressor cells (MDSCs) in tumor lesions
	is a critical molecule for Treg-mediated blood-brain barrier protection and a potential target to optimize Treg therapy for stroke
	governs DNA damage repair and breast cancer stem cell expansion
	CCR5 was required for maintenance of the mesenchymal phenotype of metastatic melanoma cells
	critical role of CCR5 expressed by melanoma cells in cancer progression
	is a chemokine receptor that is not expressed on neutrophils and inflammatory monocytes under homeostatic conditions
	CCR5 plays an important role for the migration of the inflammatory monocytes to infection focus during sepsis, having protective role in sepsis
	CCR2 and CCR5 are required for collaboration between macrophages and pulmonary-artery smooth muscle cells (PASMCs) to initiate and amplify PASMC migration and proliferation during pulmonary arterial hypertension (PAH) development
	expression levels of CCR1, CCR5 were higher in bone marrow mast cell progenitors (MCp) than in the peripheral blood, suggesting that CCR1 and CCR5 may mediate retention in the bone marrow
	is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

immunity/defense

text	granulocyte

PATHWAY

metabolism

signaling

signal transduction

cell-cell signaling

a component

DARC hetero-oligomerizes with the CC chemokine receptor CCR5 (DARC-CCR5 interaction impairs chemotaxis and calcium flux through CCR5)

INTERACTION

DNA

RNA

small molecule

protein	interacting with PRAF2
	interaction between CXCR4 and CCR5 to exert specific biological functions and modulate T lymphocyte responses, and cooperation between receptors represents one key strategy for the functional plasticity of chemokines
	interacting with TPST2 (involved in tyrosine sulfation of CCR5 N-terminal peptide)
	interacting with arrestins (arrestins may serve as scaffolding proteins linking CCR5 to multiple downstream signaling molecules in a biologically important primary cell type)
	NUP85 binds to the C-terminal region of CCR5 and enhances CCR5-mediated cellular chemotaxis
	CCL4 is a novel key mediator, and the peripheral CCL4-CCR5 axis contributes to neuropathic pain
	NUP85 binds to chemokine receptors CCR2 and CCR5, and amplifies chemotactic signals in leucocytes
	NUP85 is a cytoplasmic protein that binds to the membrane-proximal C-terminal regions (Pro-Cs) of chemokine receptors, CCR2 and CCR5
	interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites

cell & other

REGULATION

activated by

IL-10 (associated with increased migration of microglia in response to macrophage inflammatory protein-1 beta)

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to AIDS lymphoma to HIV disease progression, resistance or non progressive infections to West Nile virus (Omim 610379) to juvenile idiopathic arthritis (JIA) to multiple sclerosis (MS)

Variant & Polymorphism other	reduced risk of AIDS lymphoma with the CCR5-delta 32 mutation
	CCR5Delta32 is a functional variant, significantly associated with protection from developing JIA
	CCR5 delta32 mutation can be considered as a risk factor for MS

Candidate gene
Marker	CCR5 and CCL5 are potential markers for metastatic Pancreatic cancer (PC) cancer
Therapy target
	System Type Disorder Pubmed cancer digestive stomach therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways in the treatment of Gastric cancer cancer skin   novel strategies of melanoma treatment could be based on blocking CCR5/CCR5 ligand interactions cancer digestive pancreas blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression immunology infectious   targeting CCR5 might represent a therapeutic strategy for dengue fever

ANIMAL & CELL MODELS