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FLASH GENE

Symbol

CCL5

contributors: mct/npt - updated : 22-02-2016

HGNC name	chemokine (C-C motif) ligand 5
HGNC id	10632

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	clustered with several other CC cytokines in IMC1@
STRUCTURE	8.88 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

see IMC1@

MAPPING

cloned

Y

linked

N

status

provisional

Map	see CCL3L1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002985 3 - 1237 NP_002976 10 91 - 2000 11030415

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 pharynx       highly Lymphoid/Immune lymph node       moderately Nervous brain         Reproductive male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Connective adipose     highly Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two adjacent cysteines
	two short N terminal beta-strands in each monomer
	a conserved, positively charged BBXB motif is key for the binding of CC chemokines to glycosaminoglycan (GAG)
	a C terminal alpha helix packing against a three-standed antiparallel beta-sheet

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to murine CCL5
	homolog to Drosophila eg:bacr25b3.3
	homolog to C.elegans Y32g9a.l

Homologene

FAMILY

intercrine beta (chemokine CC) family

CATEGORY

adhesion , immunity/defense , signaling cytokine

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm
text	secreted

basic FUNCTION	monocyte, eosinophil, basophil, specific, activated T cell and dendritic cell
	functioning as a chemoattractant for blood monocytes, memory T helper cells and eosinophils
	causing the release of histamine from basophils and activating eosinophils
	plays a crucial role for tumor invasion in the interplay of tissue resident stem cells from the fat tissue and breast cancer cells
	could participate in the inflammation of obese WAT (white adipose tissue) by recruiting blood monocytes and exerting antiapoptotic properties on WAT macrophages
	one of the major HIV-suppressive factors produced by CD8+ cells
	is a proinflammatory chemokine that regulates the trafficking of Th1 T cells, macrophages, dendritic cells, and natural killer cells, mediated by activation of the receptors CCR1, CCR3, and/or CCR5
	activates GLI2 via PI3K/AKT signaling)
	play an important role in the formation of granuloma during infection with Mycobacterium tuberculosis
	important role in sustaining CD8 T cell responses during a systemic chronic viral infection
	proinflammatory chemokine known to activate leukocytes through its receptor, CCR5
	role for CCL5-mediated glucose uptake and ATP accumulation to meet the energy demands of chemotaxis in activated T cells
	CCL5 and CCL3 are critical for immune surveillance and inflammation
	CCL5 is a chemotactic cytokine, and its expression and secretion are regulated in T cells

CELLULAR PROCESS	cell communication
	cell migration & motility

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation

text	immuno-regulatory and inflammatory calcium Ca2+ homeostasis

PATHWAY

metabolism

signaling

signal transduction

cell-cell signaling

a component	dimerisation occurs between the N termianl region of each monomer
	CCL5-GLI2-IL6 axis in the stromal microenvironment regulating Ig secretion by malignant cells
	monomeric form of CCL5 is sufficient to cause cell migration, but its propensity for aggregation is essential for migration, T cell activation and apoptosis, and HIV entry into cell

INTERACTION

DNA

RNA

small molecule

protein	binding to CCR1, CCR3, CCR4
	activating a defined profile of at least 42 genes in monocytes
	interacting with CCL5 (to protect against virus-inducible apoptosis and to influence host defense against common paramyxoviral infections)
	CCL5 may contribute to modulation of I-13 production and F2R expression in mast cells, through which participates in the mast cell related inflammation
	CCL5-GLI2-IL6 interaction in B cell malignancies regulates immunoglobulin secretion
	adiponectin stimulates release of CCL2, CCL3, CCL4, CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired
	stimulated IL6 secretion in WM (Waldenstrom macroglobulinemia) stromal cells resulting in increased IgM secretion by WM malignant cells via the JAK/STAT signaling pathway
	IL15 can signal via IL15RA, JNK, and NFKB1 to drive CCL5 production by myeloid cells
	CCL5 simultaneously activates AMPK and MTOR signaling cascades to regulate glucose uptake and chemotaxis in activated T cells
	KLF13 controls the late (3-5 days after activation) expression of CCL5 in T lymphocytes and that KLF13 itself is translationally regulated through the 5prime -untranslated region of its mRNA
	FLI1 drives transcription from the CCL5 promoter in a dose-dependent manner
	ETS1, another Ets family member, and FLI1 drive transcription from the CCL5 promoter, although FLI1 transactivation was significantly stronger

cell & other

REGULATION

induced by	mitogens
		TNF alpha

repressed by

IL17 (inhibiting of TNF alpha induction)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   of CCL5 and median chemokine receptor 7 (CCR7) mRNA expression in localized scleroderma lesions as compared to healthy controls constitutional     --over   in both serum and synovial fluid of rheumatoid arthritis tumoral     --over   in Waldenstrom macroglobulinemia, and CCL5 levels positively correlated with features of disease aggressiveness such as elevated IgM levels and bone marrow involvement

Susceptibility

to emphysema in COPD to pulmonary tuberculosis (PTB) to Kawasaki disease (KD) to oral cancer

Variant & Polymorphism SNP	increasing the risk of emphysema in COPD
	SNPs in CCL5-28 and -403 genes could increase the risk to have oral cancer
	haplotype A-C-C and the diplotype G/A-T/C may be associated with resistance to PTB
	CCL5 -403A variant may be associated with coronary involvement in KD

Candidate gene
Marker	may serve as a useful marker of rheumatoid arthritis activity
	CCR5 and CCL5 are potential markers for metastatic Pancreatic cancer (PC) cancer
Therapy target
	System Type Disorder Pubmed digestive liver   successful therapeutic approach to reduce experimental liver fibrosis by antagonizing CCL5 receptors cancer hemopathy   a potential target for the treatment of Waldenstrom macroglobulinemia cancer digestive stomach therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways in the treatment of Gastric cancer cancer digestive pancreas blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression

ANIMAL & CELL MODELS