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FLASH GENE

Symbol

ADAMTS9

contributors: mct - updated : 24-01-2019

HGNC name	ADAM metallopeptidase with thrombospondin type 1 motif, 9
HGNC id	13202

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart         Endocrine pancreas         Hearing/Equilibrium ear       predominantly Nervous brain           nerve       highly   spinal cord         Reproductive female system ovary       Respiratory lung           respiratory tract larynx     moderately Urinary kidney         Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Nervous central

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	ubiquitous

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a 18 aa signal sequence of 2.1 kda
	a peptidase M12B
	a disintegrin-like domain
	fifteen thrombospondin type 1 (TSP1) domains
	a spacer domain without cysteine residue
	a unique C-terminal domain called the "GON domain"

conjugated

GlycoP , MetalloP

isoforms

Precursor

a 1917 aa proprotein of 214.4 kda given a 1648 aa mature protein of 184.2 kda

HOMOLOGY

interspecies	homolog to C.elegans Gon1
	homolog to rattus Adamts9 (88.2 pc)
	homolog to murine Adamts9

Homologene

FAMILY

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family

CATEGORY

chaperone/stress , enzyme , regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,cytoplasm,cytoskeleton,intermed filament
text	proteinaceous extracellular matrix
	localizes near basal bodies of primary cilia, and endocytosis is required for the localization of ADAMTS9 near the basal bodies

basic FUNCTION	cleaving the large aggregating proteoglycans, aggrecan and versican
	acting as an intramolecular chaperone whose glycosylation is critical for secretion of the mature enzyme (propeptide activity)
	is a putative tumor suppressor gene in nasopharyngeal carcinoma (NPC) that is significantly associated with lymph node metastases
	participates in melanoblast development and is a tumor suppressor in esophageal and nasopharyngeal cancer
	ADAMTS9 is a novel, constitutive, endogenous angiogenesis inhibitor that operates cell-autonomously in ECs via molecular mechanisms that are distinct from those used by ADAMTS1
	novel function of ADAMTS9 in the ER that promotes protein transport from the ER to the Golgi (this function is GON-domain dependent but protease activity independent)
	is a critical tumor suppressor of gastric cancer progression at least in part through suppression of oncogenic AKT/MTOR signaling
	potential role of ADAMTS9 in the remodeling of the ECM in these structures by degradation of versican

CELLULAR PROCESS	cell life, cell death/apoptosis
	protein, degradation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

protein

signaling

glycoprotein catabolic process

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+ (1 ion per subunit)

protein	PADI2 regulates the expression of the TNFRSF1B, ADAMTS9, and RAB6B transcripts in mast cells
	is a cytokine-inducible gene that contains binding sites for NFKB1 within its promoter region
	NFKB1 may be involved in IL1B-induced activation of ADAMTS9 in human chondrocytes

cell & other

REGULATION

induced by

the pathways MAPK and NFKB, thought to be responsible pathways for the induction of ADAMTS9 gene

Other

precursor cleaved by a furin endopeptidase

ASSOCIATED DISORDERS

corresponding disease(s)

NPHP21

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in hereditary renal tumors tumoral         in gastric cancer cell lines tumoral         by epigenetic disruption in colorectal cancer

Susceptibility

to type 2 diabetes

Variant & Polymorphism other	ADAMTS9 genetic risk variants were associated with type 2 diabetes
	ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   ADAMTS9 is a potential novel mode of treating insulin resistance.

ANIMAL & CELL MODELS

mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity