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FLASH GENE

Symbol

NCF1

contributors: npt/mct - updated : 04-11-2016

HGNC name	neutrophil cytosolic factor 1
HGNC id	7660

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Lymphoid/Immune lymph node       highly   spleen       highly Respiratory lung       highly

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic neutrophil

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two SH3 domains containing cytosolic component of the NADPH oxidase, 47kDa
	a single copy of the PX (PHOX) domain
	C-terminal tail is critical for stabilizing its autoinhibited structure

HOMOLOGY

Homologene

FAMILY

CATEGORY

enzyme , immunity/defense

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
text	translocated to the plasma membrane after activation

basic FUNCTION	p47-phox (NCF1), oxygen dependent mechanism of phagocytosis
	reduction of oxygen to O-2 at the expense of NADPH, the O2-generated is the precursor of potent oxidant used to kill the invading microorganisms (electron transfer from NADPH to molecular oxygen)
	mediating formation of reactive oxygen intermediates (ROI) which play an important role in host defense and autoimmunity (Greve 2008)
	novel role of NCF1 subunit beyond and independent of nicotinamide adenine dinucleotide phosphate oxidase activity as a regulator of cortactin and adaptive cytoskeletal remodeling, leading to a paradoxically enhanced susceptibility to biomechanical stress and heart failure
	NCF1 and RAC2 accumulate only transiently at the phagosome at the onset of NADPH activity and detach from the phagosome before the end of ROS production
	is a key regulatory subunit of NADPH oxidase

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

inflammation

PATHWAY

metabolism

signaling

a component	component of NADPH oxidase system cypb245
	forming a cytosolic precomplex with NCF2 and NCF4
	component of an intracellular complex made of CYBB, CYBA, NCF2, NCF4 in unstimulated endothelial cells
	component of the leukocyte NADPH oxidase complex mediating formation of reactive oxygen intermediates (ROI)(Greve 2008)

INTERACTION

DNA

RNA

small molecule

protein	binding by its SH3 domain to both CYBA and NCF2
	is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells
	NMRAL1 regulates NCF1 through inhibition of NFKB activity
	CYBB activation requires membrane translocation of the NCF1 subunit and is linked to heart failure
	CYBB, modulated at least in part by NCF1, mediates early stage compensatory vascular collateral development via a process dependent upon peroxide generation
	ANGPT1 requires oxidant signaling through NCF1 to promote endothelial barrier defense
	TLR8, is involved in priming of human neutrophil ROS production by inducing the phosphorylation of NCF1 and MAPK14 and PIN1 is also involved in this process
	NCF1 is the key regulatory component of the phagocytic NADPH oxidase 2 (CYBB) complex

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

NCF1D

related resource

NCF1base: Mutation registry for autosomal recessive chronic granulomatous disease (CGD), deficiency of p47phox

Susceptibility

to rheumatoid arthritis

Variant & Polymorphism other	copy number variation of the gene NCF1 is associated with rheumatoid arthritis

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

female mice lacking Ncf1 have altered adipose tissue gene expression and are protected against high fat-induced obesity