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FLASH GENE

Symbol

CSF2

contributors: mct - updated : 28-01-2019

HGNC name	colony stimulating factor 2 (granulocyte-macrophage)
HGNC id	2434

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Respiratory lung

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic granulocyte Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

GlycoP

mono polymer

monomer

HOMOLOGY

interspecies	homolog to murine Csf2
	homolog to C.elegans y71f9b.1

Homologene

FAMILY

GM-CSF family

CATEGORY

immunity/defense , signaling cytokine

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	stimulating the growth and differentiation of hematopoietic precursor cells from various lineages (granulocytes, macrophages, eosinophils and erythrocytes)
	in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells
	CASC3 and CSF2 are involved in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis
	CSF2 signaling activates mitogen-activated protein kinase, followed by the upregulation of CASC3 and CFLAP, resulting in fibroblast-like synoviocyte hyperplasia in rheumatoid arthritis
	may accelerate cell growth and inhibit cell death via PKC activation in the cell lines and also seems to reverse growth suppression and cell death induced by PKC inhibition
	IL2 and CSF2 are regulated by DNA demethylation during activation of T cells, B cells and macrophages
	CSF2 is important in vaccine-induced CD8(+) T cell immunity through the regulation of nonlymphoid tissue Dendritic cells (DCs) homeostasis rather than control of inflammatory DCs
	IL21 and CSF2 exhibit cross-regulatory actions on gene regulation and apoptosis, regulating conventional dendritic cells (cDCs) numbers and thereby the magnitude of the immune response
	haemopoietic growth factor that is used in the clinic to correct neutropaenia, usually as a result of chemotherapy
	is a key factor in Th17 driven autoimmune inflammatory conditions
	CSF1 and CSF2 can regulate the development and function of the mononuclear phagocyte system (MPS)
	has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation
	critical role in immune modulation and hematopoiesis
	has inhibitory effects on tumor growth and metastasis, but also exerts stimulatory effects on tumor progression

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

immunity/defense

text	control of cell proliferation

PATHWAY

metabolism

signaling

CSF2 signaling controls a pathogenic expression signature in CCR2(+)Ly6C(hi) monocytes and their progeny, which was essential for tissue damage

a component

INTERACTION

DNA

RNA

small molecule

protein	MMP2 and MMP14 (upregulated by CSF2 in head and neck cancer cells)
	nuclear activation of REL not only regulates the initiation of CSF2 and IL2 gene activation in response to T cell activation, but also the termination of these gene responses following the removal of the activating signal
	NFKB1 controls IL2 and CSF2 expression during T cell development and activation process
	accelerated the G1/S phase transition in endothelial progenitor cells (EPCs) by upregulating the expression of CCND1 and CCNE1
	CSF2 has a lung-specific role in the perinatal development of alveolar macrophages (AMs) through the induction of PPARG in fetal monocytes
	TRAF6 is required for CSF2-induced ubiquitination and activation of AKT1
	MAFB is a negative regulator of CSF2 signaling in microglia
	RNF13 affects the concentration of CSF2 in tumor-bearing lungs, leading to a reduction in the colonization of metastatic tumor cells in the lung
	upregulation of CSF2 and CSF1 production by endothelial cells, an effect that appears to be mediated by NFKB1 and to be independent of IL1, may be an additional mechanism through which IL33 contributes to inflammatory activation of the vessel wall
	DPP4/CD26 enzymatically cleaves select penultimate amino acids of proteins, including colony-stimulating factors (CSF2), and has been implicated in cellular regulation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   increased pulmonary CSF2 production in response to infection is primed by the microbiota through IL17A constitutional       gain of function in periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome with activation of IL8

Susceptibility

to asthma to rheumatoid arthritis

Variant & Polymorphism	variant ile 117 maybe a risk factor for atopic asthma

Candidate gene
Marker
Therapy target	antibody specific for cytokine or receptor as therapeutic targets in rheumatoid arthritis

ANIMAL & CELL MODELS

in Csf2 gene-deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil dynamics in antigen-induced peritonitis suggested that Csf2 was acting, in part, systemically to maintain the inflammatory reaction