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FLASH GENE

Symbol

MMP13

contributors: mct/npt/pgu - updated : 27-03-2016

HGNC name	matrix metalloproteinase 13 (collagenase 3)
HGNC id	7159

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Digestive esophagus       highly Endocrine neuroendocrine pituitary       Hearing/Equilibrium ear inner cochlea   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Connective cartilage

cells

System Cell Pubmed Species Stage Rna symbol   chondrocyte Skeleton osteoblast

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	chondrocytes, skeleton

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a cysteine residue essential for latency and involved in autocatalytic activation
	a catalytic domain with the zinc-binding site (the cysteine switch)
	a hinge region
	a hemopexin-like C terminal domain

conjugated

HemoP , MetalloP

HOMOLOGY

interspecies

homolog to murine Mmp13

intraspecies

homolog to MMP8

Homologene

FAMILY	matrix metalloproteinase family of neutral endopeptidase
	peptidase M10A family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	regulator of matrix remodeling
	collagenase III, cleaving preferentially the type II collagen
	playing a critical role in bone metabolism and homeostasis, and in tumor invasion and metastasis
	involved in the degradation of extracellular matrix, prerequisite for invasive and metastatic behavior of solid tumors
	involved in the degradation of cartilage
	osteoclast activation
	playing a critical role in development of growth plate cartilge and in endochondral ossification
	anti-inflammatory activity
	play a critical role in cartilage destruction and have an important rolen in cartilage formation
	with MMP9 play a role in endochondral ossification
	mediates cell cycle progression in melanocytes and melanoma cells
	might be directly involved in the loop promoting pre-osteoclast differentiation and activity
	has a pivotal, rate-limiting function in cartilage remodeling and degradation due to its specificity for cleaving type II collagen
	osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP13 and is essential for the maintenance of bone quality
	important role in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis
	MMP13 may directly and indirectly promote tumor angiogenesis
	promoted the secretion of VEGF from fibroblasts and endothelial cells

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

inflammation

text	antiinflammatory

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	binding TIMPs in a 1:1 stoechiometry
	interacting with RUNX2 (phosphorylation of RUNX2 sites necessary for PKA stimulated MMP13 promoter activation and this event may be critical for bone remodeling)
	HDAC4 is a basal repressor of MMP13 transcription, and PTH regulates HDAC4 to control MMP13 promoter activity
	IL6 increased the migration and expression of MMP13 in chondrosarcoma cells
	NOV increased the migration and expression of matrix metalloproteinase MMP13 in chondrosarcoma cells
	CEBPB and RUNX2 cooperatively enhanced promoter activity of MMP13 through specific binding to a CEBP-binding motif and an osteoblast-specific cis-acting element 2 motif as a protein complex
	WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
	novel role for ELF3 as a procatabolic factor that may contribute to cartilage remodeling and degradation by regulating MMP13 gene transcription
	possible involvement of S100A12 in the development of osteoarthritis (OA) by up-regulating MMP13 and VEGFA via MAPK14 and NFKB1 pathways
	MMP13 is an important target of Osterix (SP7)
	physical and functional interaction between SP7 and RUNX2 were necessary for the induction of MMP13 during endochondral ossification
	direct regulatory role for SP7 in MMP13 gene expression in osteoblasts
	promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP13
	IL6 mediates suppression of ACAN and induction of MMP13 expression by NOTCH1 in chondrocytes
	inhibition of MMP13 expression through GDF5 stimulation is mediated by DKK1
	MMP13 proteolyzes FBLN1 and CALU protects FBLN1 from cleavage by MMP13
	IL32 stimulation promotes the invasion and motility of osteosarcoma cells, possibly via the activation of AKT1 and the upregulation of MMP13 expression

cell & other

REGULATION

activated by	proteinases and plasmin, and others MMPs (MMP14)
	MAF (can significantly enhance MMP13 promoter activity via the AP-1 site)

induced by

FOXO3

inhibited by	IL1 and RUNX2 in chondrocytic cells
	TFPI2

repressed by

ANKRD1 (in association with factors such as nucleolin, represses likely MMP13 transcription) )

ASSOCIATED DISORDERS

corresponding disease(s)

SEMD2 , MAND2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast carcinoma, squamous cell carcinomas of head and neck and vulvar squamous cell carcinoma constitutional     --over   overexpressed in rheumatoid arthritis and inabdominal aortic aneurysm tumoral     --over   in renal cell carcinoma bone metastasis and is induced by TGF-beta1

Susceptibility

to coronary artery disease

Variant & Polymorphism other	MMP13 intron polymorphism rs640198 is associated with the severity of coronary artery disease

Candidate gene	for SEMD2
Marker	could be a potential prognostic marker for colorectal cancer patients
Therapy target

ANIMAL & CELL MODELS