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FLASH GENE

Symbol

ADAMTS4

contributors: mct - updated : 18-09-2015

HGNC name	ADAM metallopeptidase with thrombospondin type 1 motif, 4
HGNC id	220

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005099 9 - 4410 NP_005090 98 837 - 2010 2066492

EXPRESSION

Type	restricted

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 Nervous brain           nerve cranial nerve       Respiratory respiratory tract trachea       Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   chondrocyte

cell lineage
cell lines	osteoarthritic cartilage
fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

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, including a disintegrin domain (Dis)
	a thrombospondin domain
	a cysteine-rich domain (Cysr)
	a spacer domain (Sp) without cysteine residues
	a C- terminal TSP-like module implicated in aggrecanolytic activity, and governing the specificity of the enzymes by modulating substrate binding, and affect the structure around the active site, favouring interaction with TIMP3

conjugated

MetalloP

isoforms

Precursor

pro-form of ADAMTS-4 is not catalytically active and only a limited number of mechanisms mediate its N-terminal activation

HOMOLOGY

interspecies

homolog to murine secretory protein

Homologene

FAMILY

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

CATEGORY

adhesion , enzyme

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	degrading the chondroitine sulfate proteoglycan (brevican)
	playing a pivotal role in inflammatory joint disease, and in cartilage aggrecan degradation
	epigenetically regulated and plays a role in aggrecan degradation in osteoarthritis
	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
	proteinase thought to be involved in processes ranging from cartilage metabolism to ovarian follicle development
	ADAMTS1 and ADAMTS4 play redundant and essential roles in perinatal kidney development

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor,
	Zn2+

protein	aggrecan (binding by TPS1motif) for cleavage of aggrecan
	interacting with adaptor proteins and RAS, that synergistically regulate IL1-induced ADAMTS4 expression in chondrocytes (
	ADAMTS4 cleaves RELN in an isoform-specific manner

cell & other

REGULATION

induced by

interleukin 1

inhibited by	TIMP3
	alpha(2)-macroglobulin in a concentration-dependent manner,

Other

its expression was found to be regulated by EWS-FLI1 fusion gene-dependent manner

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   required to inhibit aggrecan degradation in human OA cartilage tumoral     --over   in Ewing sarcoma constitutional     --over   in acute coronary syndrome constitutional     --low   in the maternal and cord blood were lower in the preeclampsia group than in the control group

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	is potentially a novel tumor marker for Ewing sarcoma
	its expression may be a valuable marker for predicting the severity of acute coronary syndrome
Therapy target

ANIMAL & CELL MODELS