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FLASH GENE

Symbol

ADAM8

contributors: mct - updated : 12-02-2016

HGNC name	ADAM metallopeptidase domain 8
HGNC id	215

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 spleen       highly   thymus       highly Nervous brain       highly

tissue

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

cells

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	domains similar to hemorrhagic snake venom proteins (HSVP) with a prodomain
	a Zn-binding site metalloproteinase
	a disintegrin-like domain
	a cysteine-rich domain
	an EGF-like repeat
	a transmembrane domain
	a proline-rich SH3 cytoplasmic tail suggesting that it interacts with other cytoplasmic proteins

conjugated

GlycoP , MetalloP

HOMOLOGY

interspecies

homolog to murine Adam8

Homologene

FAMILY	peptidase family M12B
	ADAM (a disintegrin and metalloprotease domain) family

CATEGORY

adhesion , antigen

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	present both on the cell surface and in intracellular granules of human neutrophils

basic FUNCTION	playing an important role in osteoclast formation and differentiation
	involved in cell-cell and cell-matrix interactions
	may be contributing to ectodomain shedding of CD23
	involved in ectodomain shedding of membrane proteins and is linked to inflammation and neurodegeneration
	may play a significant role in tumor invasion that may be detrimental to patients survival
	stimulates osteoclast differentiation
	may have a potential relevant role in the function of neutrophils during inflammatory response
	stimulates osteoclast (OCL) formation
	modulates the expression and function of SELPLG
	is the primary protease for the alpha-cleavage of PRNP that appears self-regulated through ADAM8 in muscle
	mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components
	mediates an enhanced invasiveness of neutrophils into injured muscle fibers by the removal of their adhesiveness to blood vessels after infiltration into interstitial tissue
	role in pancreatic cancer signalling
	could promote the proliferation of normal hepatocytes and render hepatoma carcinoma cells more resistant to apoptosis to play important roles during the progression of hepatocellular carcinoma

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	CD23
	is both associated with SELPLG through the ezrin–radixin–moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor
	is the primary protease responsible for the alpha-cleavage of PRNP in muscle cells
	ADAM8 can perform alpha-cleavage of PRNP and PRNP can regulate ADAM8 expression

cell & other

REGULATION

Other

N-glycosylation is essential for processing, localization, stability, and activity of ADAM8

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function in various tumors including lung and brain tumors tumoral     --over   of novel truncated forms of ADAM8, associated with increased invasive abilities and osteoclastogenic properties, and correlated with the early development of metastatic lesions tumoral     --over   in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs) tumoral     --over   associated with poor overall survival in patients with hepatocellular carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	prognostic marker for renal cell carcinomas and the best predictor of distant metastasis
Therapy target
	System Type Disorder Pubmed allergy     potential target for therapeutic intervention in allergy and inflammation cancer digestive pancreas ADAM8 is a target for PDAC therapy cancer reproductive breast represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination cancer digestive liver may be a potential target of antiangiogenic therapy for HCC

ANIMAL & CELL MODELS

skeletal muscle of dystrophin-null mice, an animal model for Duchenne Muscular Dystrophy, deteriorates by the lack of Adam8, which is characterized by increased area of muscle degeneration and increased number of necrotic and calcified muscle fibers