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FLASH GENE

Symbol

MMP8

contributors: mct - updated : 01-09-2021

HGNC name	matrix metalloproteinase 8 (neutrophil collagenase)
HGNC id	7175

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE
text	member of the MMP cluster
STRUCTURE	13.17 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002424 10 - 3055 NP_002415 41.9 467 - 2021 33556788 NM_001304442 11 - 3143 NP_001291371 - 444 - 2021 33556788 NM_001304441 11 - 3146 NP_001291370 - 444 - 2021 33556788

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 Lymphoid/Immune thymus       highly Reproductive female system placenta       Skin/Tegument skin       highly

tissue

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

cells

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

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	cytotrophoblastic cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

four hemoplexin-like domains

conjugated

HemoP , MetalloP

HOMOLOGY

interspecies	homolog to rattus Mmp8 (72.9pc)
	homolog to murine Mmp8 (74.5pc)

Homologene

FAMILY

peptidase M10A family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,cytosolic,granule
text	secreted, extracellular space, extra cellular matrix

basic FUNCTION	regulator in matrix remodeling
	degradation of type I, II, III collagens, preferentially the type I collagen
	degrading fibrillar collagens imparting strength to the fetal membranes
	abilitiy to inhibit melanoma progression (Palavalli 2009)
	has an inhibitory effect on cancer metastasis (Decock 2007)
	is a key player in atherogenesis
	is an essential mediator in Systemic inflammatory response syndrome (SIRS)
	evidence of the most relevant regulatory pathways and activities mediated by MMP8 in atherogenesis
	role of MMP8 in macrophage differentiation and polarization
	macrophage-derived MMP8 is a regulator in SMC differentiation from adventitia stem/progenitor cells (AdSPCs) and neointimal smooth muscle cells (SMCs) in response to injury
	MMP8 participates in eye diseases including xerophthalmia and retinal disease
	MMP8 can facilitate RPE cells proliferation and migration via modulating cell apoptotic activity and secretion of inflammatory factor, thus participating in Rhegmatogenous retinal detachment (RRD) pathogenesis and progression

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	binding two ions Zn2+ per subunit
	binding three ions Ca2+ per subunit

protein	binding TIMPs in a 1:1 stoechiometry
	MMP8 plays an important role in intestinal ischemia-reperfusion (I/R) injury through mechanisms involving increased inflammation and loss of claudin-3
	FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility

cell & other

REGULATION

activated by

autocatalytic cleavage

inhibited by

TIMPs and TFPI2

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in ovarian cancer with invasive potential constitutional       gain of function in chronic obstructive pulmonary disease constitutional     --over   at the site of abdominal aortic aneurysm rupture tumoral somatic mutation       five mutations reducing MMP enzyme activity in melanoma (Palavalli 2009) constitutional     --over   intraplaque MMP8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound (Turu 2006) constitutional     --over   increased local MMP8 expression in the periodontal connective tissues of smokers with periodontal disease (Liu 2006) constitutional     --over   serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome in men (Tuomainen 2007)

Susceptibility

to preterm premature rupture of membranes bacterial vaginosis is associated with increased levels of matrix metalloproteinase-8(MMP-8) in vaginal fluid of pregnant women (Diaz-Cueto 2006) to osteonecrosis of the femoral head (ONFH)

Variant & Polymorphism SNP , other	SNP associated with preterm premature rupture of membranes
	a promoter SNP with its minor allele (T) associating with reduced susceptibility to lymph node metastasis in breast cancer (Decock 2007)
	polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk (González-Arriaga 2008)
	remarkable association between rs11225394 in MMP8 gene and an increased risk of ONFH and a significant association between MMP8 rs2012390 and the decreased risk of ONFH

Candidate gene
Marker	increase in the duration of response to the cold test was associated with an increase in MMP8 levels in teeth with pulpitis
Therapy target

ANIMAL & CELL MODELS