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FLASH GENE

Symbol

ADAMTS5

contributors: mct - updated : 25-08-2016

HGNC name	ADAM metallopeptidase with thrombospondin type 1 motif, 5
HGNC id	221

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal sequence
	a propeptide domain
	a reprolysin-type catalytic domain
	a zinc catalytic domain
	non-catalytic ancillary domains
	a disintegrin domain (Dis)
	a thrombospondin domain
	a cysteine-rich domain (Cysr)
	a spacer domain (Sp)
	a second thrombospondin domain follows the spacer domain
	one C terminal TSP-like module, that govern the specificity of the enzymes by modulating substrate binding
	CysR and Sp domains greatly increased its aggrecanolytic activity
	C-terminal domains affect the structure around the active site, favouring interaction with TIMP3

conjugated

MetalloP

isoforms

Precursor

HOMOLOGY

interspecies

homolog to murine Adamts5

Homologene

FAMILY

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

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	cell surface adhesion protein cleaving the cartilage proteoglycan aggrecan, involved in the destruction of aggrecan in arthritic disease
	may play a role in glioma cell invasion through the cleavage of brevican
	major aggrecanase in cartilage metabolism and pathology
	(aggrecanolytic activity of ADAMTS5 was much greater than ADAMTS4)
	ADAMTS4 and ADAMTS5 not only play roles in the breakdown of cartilage extracellular matrix in osteoarthritis, but also mediate processing of matrilins in the secretory pathway
	in the growth plate ADAMTS5, and not ADAMTS4, has a physiological function in the intracellular processing of matrilins and potentially of other extracellular matrix proteins
	role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function
	a function of ADAMTS5 in dermal fibroblasts is potentially to maintain optimal versican content and pericellular matrix volume by continually trimming versican in hyaluronan-versican aggregates

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

locomotion

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	interaction with Syndecan-4 (controls the activation of ADAMTS5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of MMP3)
	LRP1 dictates physiological and pathological catabolism of aggrecan in cartilage and is a key modulator of the extracellular activity of ADAMTS5
	RELA is a potent transcriptional activator of ADAMTS5 in chondrocytes during osteoarthritis development
	ADAMTS4 and ADAMTS5 may destabilize the filamentous network in the extracellular matrix by cleaving MATN2 in both homo-oligomers and hetero-oligomers
	role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS5 function and MMP3 expression

cell & other

REGULATION

induced by

alpha(2)-macroglobulin in a concentration-dependent manner

inhibited by

TIMP3

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in glioblastoma cells constitutional     --low   required to inhibit aggrecan degradation in osteoarthritis cartilage constitutional     --low   during chondrogenesis

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

adult Adamts5(-/-) mice are viable, they do not recover from developmental valve anomalies, but have myxomatous cardiac valves