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FLASH GENE

Symbol

S100A9

contributors: mct/npt - updated : 23-02-2016

HGNC name	S100 calcium binding protein A9
HGNC id	10499

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1q21.3      Physical location : 153.330.329 - 153.333.502
Genatlas name	calprotectin
Synonym name	cystic fibrosis associated antigen, myeloid-related protein 14
	S100 calcium binding protein A9 (calgranulin B)
	migration inhibitory factor-related protein 14
	leukocyte L1 complex heavy chain
	calprotectin L1H subunit
	calgranulin B
Synonym symbol(s)	CAGB, CFAG, MRP14, MIF, L1AG, NIF, S109, 60B8AG, CGLB, LIAG, MAC387, P14

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	3.17 kb     3 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site   transcription factor
text structure	TP53 binding sites in the promoter

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see EDC@

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002965 3 - 586 NP_002956 13.11 114 - 2009 19122197

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 spleen       highly Respiratory lung       highly Skin/Tegument skin         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Epithelial barrier lining epidermis     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Blood/Hematopoietic neutrophil Homo sapiens Lymphoid/Immune macrophage Homo sapiens Skin/Tegument keratinocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two calcium binding domains with an EF-hand motif
	one S100 specific Nter
	one classical Cter
	a central core polypeptide domain of S100A9 in the calprotectin complex that plays a crucial role in epithelial resistance to bacterial invasion (Champaiboon 2009)

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies

homolog to murine S100a9

Homologene

FAMILY

S100 family

CATEGORY

adhesion , regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation
	playing a role in the development of epithelial skin tumors
	playing a role in the inflammatory response to lipopolysaccharide by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site
	induced adhesion only to fibronectin
	stimulated neutrophil adhesion to this extracellular matrix protein
	playing a a pivotal role during sepsis
	potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in Alzheimer disease (AD)
	S100A8/S100A9 levels are likely to be maintained in conditions where IL10 is raised, and these proteins may contribute to viral persistence in patients infected by some RNA viruses
	TP53 transcriptional target, inducing cellular apoptosis in a partly TP53-dependent manner and mediating the TP53 apoptosis pathway (Li 2009)
	bacterial flagellin induces the upregulation of S100A8/S100A9 via a TLR5-dependent mechanism in epidermal keratinocytes (PMID/
	pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis
	S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin
	S100A8 and/or S100A9 promote endothelial cell proliferation, survival, and angiogenesis both directly and by inducing keratinocytes to produce pro-angiogenic cytokines
	S100A8 and/or S100A9 promote endothelial cell proliferation, survival, and angiogenesis both directly and by inducing keratinocytes to produce pro-angiogenic cytokines
	S100A8 and S100A9 are Ca(2+)-binding proteins that are associated with acute and chronic inflammation and cancer
	S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma
	role for S100A8 and S100A9 in redox-sensitive biological responses, including pro-inflammatory cytokine secretion (
	has a protective role in inflammation-induced skin carcinogenesis
	S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	constituent of epidermal differentiation complex
	heterodimerizing with S100A8 for NADPH oxidase activation in neutrophils, S100A8/S100A9-heterodimer calprotectin are formed in the absence of calcium, tetramerization is strictly calcium-dependent

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	interacting with S100A8 (S100A8-S100A9 complexes amplify the endotoxin-triggered inflammatory responses of phagocytes)
	S100A8 and S100A9 interact non-covalently, and that they function coordinately and/or independently as homodimers or heterodimers, depending on the microenvironment
	functional partner for NADPH oxidase activation contrary to S100A9, however, the loading with calcium and a combination with phosphorylated S100A9 are essential
	S100A12, S100A8, S100A9 has no direct effect on cholesterol efflux in macrophages, but rather promotes the secretion of IL22, which then directly reduces cholesterol efflux in macrophages by decreasing the expression of ABCG1
	S100A9 protein is a critical regulator of TLR3 trafficking
	CD14 is a co-receptor of TLR4 in the S100A9-induced cytokine response
	S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in ulcerative colitis and Crohn's disease and psoriasis tumoral     --low   in squamous cell carcinoma of the head and neck, also oesophageal constitutional     --over   in numerous inflammatory diseases, such as sepsis, rheumatoid arthritis, inflammatory bowel disease, vasculitis and cancer constitutional     --over   from keratinocytes in psoriatic lesions tumoral     --over   elevated levels of S100A8 or A9 in the ductal fluid, a near absence of pancreatic enzymes, and high levels of mucins were found to have significantly worse prognosis in pancreatic cancer constitutional     --over   overexpression of S100A8-S100A9 in neurons is an early step in oncogenic KRAS-induced gliosis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	S100A8 and S100A9 may serve as biomarkers for the detection of renal cell carcinoma
	potential marker of disease activity in patients with psoriatic arthritis
Therapy target
	System Type Disorder Pubmed dermatology skin   inhibiting S100A8 and/or S100A9 may be a novel therapy targeting various molecular events involved in the initiation of psoriasis

ANIMAL & CELL MODELS

S100a9(-/-) mouse is viable and phenotypically normal