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FLASH GENE

Symbol

MMP7

contributors: mct/pgu - updated : 20-03-2015

HGNC name	matrix metallopeptidase 7 (matrilysin, uterine)
HGNC id	7174

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal sequence
	a prodomain with a cysteine residue,essential for latency and involved in autocatalytic activation
	a catalytic domain with the zinc-binding site and lacking the hemopexin-like (PEX) C terminal domain

conjugated

HemoP , MetalloP

isoforms

Precursor

pro-form consists of only a propeptide and a catalytic domain and lacks the C-terminal hemopexin-like domain (.PMID: 18955490)

HOMOLOGY

Homologene

FAMILY	zinc dependent endopeptidases family
	stromelysin subclass of MMP family
	peptidase M10A family

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	extracellular
text	secreted protein, extracellular matrix

basic FUNCTION	regulator of matrix remodeling and mediator of pulmonary fibrosis (and potential therapeutic target)
	generating angiostatin fragments by hydrolyzing plasminogen
	may be responsible for the activation of prodefensins and thereby participating in innate host defense
	remodeling of elastotic areas in sun damaged skin
	required for the activation of defensin in small bowel
	processes cell surface molecules such as pro-alpha-defensin, fas-ligand, pro-tumor necrosis factor alpha, E-cadherin
	involved in adipocyte differentiation, enhanced collagen affinity, increased bioavailability of TGF beta, disrupted cell aggregation and increased cell invasion anf Fas-receptor-mediated apoptosis
	degrades casein, gelatins of type I, III, IV, V, fibronectin and elastin
	activating procollagenase
	involved in wound healing
	may regulate the activity of defensins in intestinal mucosa
	potent modulator of synaptic vesicle recycling and synaptic ultrastructure and elevated levels of the enzyme, as may occur with brain inflammation, may adversely influence neurotransmission
	involved in tumor angiogenesis, thereby contributing to malignant growth and hence associated with decreased survival
	may be involved in the aging process of human mammary epithelial cells by affecting extracellular remodeling and intracellular signaling pathways
	LAMB3, LAMC2, in conjunction with MMP7, play a key role in the progression of biliary tract cancer
	is involved in the cleavage of CDH2 and modulates vascular smooth muscle cell (VSMC) apoptosis, and may therefore contribute to plaque development and rupture
	new role for MMP7 in attenuating ciliated cell differentiation during wound repair

CELLULAR PROCESS	cell life, differentiation
	cell life, cell death/apoptosis
	nucleotide, repair
	protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor,
	binding two ions calcium Ca2+ per subunit
	binding two ions zinc Zn2+ per subunit

protein	colocalizing and regulating DEFA5
	interaction with ETS1 (contribution to the progression of HCC)
	HAS2, HAS3 and HA may mediate cellular invasion via changes in MMP7 expression
	binding TIMPs in a 1:1 stoechiometry
	directly interacts with SDC2
	MSLN enhances ovarian cancer invasion by MMP7 expression through the MAPK/ERK and JNK signal transduction pathways
	MMP7 inhibition of BMP7 induced renal tubular branching morphogenesis suggests a role in the pathogenesis of human renal dysplasia
	is a key downstream effector of FOXC1-mediated invasiveness in breast cancer
	MMP7 is a target gene of EPCAM signalling via EpICD nuclear translocation
	MMP7 is a bona fide ETV1 target gene, implicating that MMP7 upregulation is partially responsible for the oncogenic effects of ETV1 in the prostate
	in the small intestine, MMP7 is responsible for activating DEFAs, which are broad-spectrum anti-microbial peptides produced by the Paneth cells
	functions to degrade extracellular matrix and other pericellular substrates including the adherens junction protein CDH1 to promote wound healing and tissue remodeling
	regulator of CTNNB1 function in injured lung epithelium and may link extracellular proteolytic activity to cell junction disassembly and intracellular signaling

cell & other

binding of MMP7 to cell surface cholesterol sulfate (CS) is essential for the cell membrane-associated proteolytic action of the protease

REGULATION

activated by	proteinases and plasmin
	binding of sulfated glycosaminoglycans, such as heparin, chondroitin-4,6-sulfate or dermatan sulfate

inhibited by	TIMPs and TFPI2
	binding a catalytic zinc ion

Other

regulated by beta catenin/CF4

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function with ETS1 in hepatocellular carcinomas tumoral     --over   in colorectal cancer with metastasis tumoral       gain of function differentially up-regulated in germ cells teratomas constitutional     --over   in epithelium by bacterial infection, inflammation and fibrosis constitutional     --over   in congenital renal dysplasia (RD)

Susceptibility

to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma

Variant & Polymorphism SNP , other	polymorphism in the promoter increasing susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma
	snp Gly137Asp confers risk of liver cirrhosis
	functional variants of MMP7 are associated with susceptibility to H.pylori-induced precancerous gastric lesions

Candidate gene	positive expression may serve as a predictor of lymph node metastasis in gastric cancer
	elevated expression is predictor of disease recurrence of colon cancer and is related to decreased survival
	higher expression of MMP7 supports the notion of a role in the growth of lung carcinoma
Marker
Therapy target
	System Type Disorder Pubmed cancer     develop MMP7-targeted novel anti-cancer drugs that block specifically the membrane-associated proteolytic action of this MMP, thereby having restricted side effects cancer reproductive breast may be a useful therapeutic target for treatment of this disease

ANIMAL & CELL MODELS

	Paneth cells (in mice)
	MMP7(-/-) mice are resistant to LPS-induced lethality and that this resistance is correlated with reduced levels of systemic cytokines