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FLASH GENE

Symbol

CCL4

contributors: mct - updated : 06-05-2020

HGNC name	chemokine (C-C motif) ligand 4
HGNC id	10630

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17q12      Physical location : 34.431.219 - 34.433.014
Synonym name	macrophage inflammatory protein 1 beta
	small inducible cytokine A4 (homologous to mouse Mip-1b)
	lymphocyte activation gene 1
	secreted protein G-26
	protein H400
	G-26 T-lymphocyte-secreted protein
Synonym symbol(s)	ACT2, Act-2, MIP1B, SCYA4, AT744.1, MIP-1-BETA, MIP-1-beta, LAG1, G-26, MGC104418, MGC126025, MGC126026, SCYA2, SIS-gamma, HC21

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster, head to head, opposite orientation
text	separated by 14kb in head to head orientation from CCL3
	clustered in IMC1@
STRUCTURE	1.80 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (TATA box)
text structure	promoter region include a GM-CSF-like decanucleotide sequence (Baixeras 1990)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	see CCL3L1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002984 3 - 667 NP_002975 - 92 - 1990 2247088

EXPRESSION

Type	restricted

constitutive of

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 adrenal gland       highly Nervous brain       moderately Reproductive female system placenta     highly   male system prostate     highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		acid		Hydrophilic
STRUCTURE

motifs/domains

a very hydrophobic N terminus, which was predicted to be a signal peptide

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies	homolog to murine Mip-1beta (see IMC1@)
	homolog to C.elgans F59B10.5
	homolog to Drosophila eg:bacr25b3.3

intraspecies	paralog to SCYA4L1
	paralog to CCL4L1

Homologene

FAMILY	intercrine beta family
	CC subfamily (small inducible cytokine, chemokine beta)

CATEGORY

adhesion , immunity/defense , signaling cytokine

SUBCELLULAR LOCALIZATION	extracellular
text	secreted

basic FUNCTION	monocyte, chemoattractant, activated T cell and dendritic cell
	one of the major HIV-suppressive factors produced by CD8+ T cells
	playing a role in etablishement of cell polarity
	contributing to intracellular signaling and other chemokine receptor function
	promote trophoblast migration at the feto-maternal interface
	with CCL3, may directly or indirectly affect neuronal excitability, and are implicated in the etiology and pathogenesis of temporal lobe epilepsy
	principal regulator of macrophage migration and signals through CCR5
	crucial role of CCL4 in the development of dry eye syndrome in CF patients and immunopathogenesis of ocular surface changes in this disease
	CCL3 and CCL4 are chemokines crucial for immune responses towards infection and inflammation
	AR-CCL4-STAT3 axis is key regulator during prostate tumor initiation, suggesting important roles of infiltrating macrophages and inflammatory cytokines for the prostate tumorigenesis
	Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells
	macrophage-derived foam cells impair endothelial barrier function by inducing endothelial-mesenchymal transition via CCL4
	can promote tumor development and progression by recruiting regulatory T cells and pro-tumorigenic macrophages, and acting on other resident cells present in the tumor microenvironment, such as fibroblasts and endothelial cells, to facilitate their pro-tumorigenic capacities

CELLULAR PROCESS	cell life, proliferation/growth
	cell communication
	cell migration & motility

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation

PATHWAY

metabolism

signaling

signal transduction

cell-cell signaling

a component

MIP1A/MIP1B heterodimer

INTERACTION

DNA

RNA

small molecule

protein	binding to CCR8
	natural ligand for the primary human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5
	adiponectin stimulates release of CCL2, CCL3, CCL4, CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired
	CCL4 is a novel key mediator, and the peripheral CCL4-CCR5 axis contributes to neuropathic pain
	secretion of IL1A, IL1B, IL12B, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3
	TNF drives CCL4 expression in THP-1 monocytic cells/macrophages via the activation of SAPK/JNK and NFKB1 pathways

cell & other

REGULATION

induced by	mitogens
		phytohemagglutinin (in T cells)
		staphylococcus aureus (in B cells)
		lipopolysaccharide (in monocyte)
		Prokineticin 1 (induces CCL4, CXCL1 and IL8 in monocytes but not in macrophages and dendritic cells)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in CD8+ cells and CD4+ cells in sarcoidosis

Susceptibility

to AIDS

Variant & Polymorphism SNP	influencing HIV Type 1 transmission and AIDS disease progression (Omim: 609423)

Candidate gene
Marker	variations in the CCL4 gene may help to predict breast cancer progression and metastasis
	decreased preclinical CCL3 and CCL4 levels might be associated with a subsequently increased risk of nasopharyngeal carcinoma
	CCL4 rs10491121 may be a factor to predict the tumor size in oral squamous cell carcinoma (OSCC) patients
Therapy target

ANIMAL & CELL MODELS