Collagenase 3

UniProt P45452 Organism Homo sapiens Gene MMP13 EC 3.4.24.-

Also known as: MMP13

Function

Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.

Classification

Family (Pfam): PF00045 Hemopexin, PF00413 Peptidase_M10, PF01471 PG_binding_1
InterPro: Hemopexin-like_dom, Hemopexin-like_dom_sf, Hemopexin-like_repeat, Hemopexin_CS, M10A_MMP, MetalloPept_cat_dom_sf, Pept_M10_metallopeptidase, Pept_M10A, Pept_M10A_Zn_BS, Peptidase_Metallo, Peptidoglycan-bd-like, PGBD-like_sf
Functional cluster: Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 49

1EUB NMR
1FLS NMR
1FM1 NMR
1PEX X-ray 2.70A
1XUC X-ray 1.70A
1XUD X-ray 1.80A
1XUR X-ray 1.85A
1YOU X-ray 2.30A
1ZTQ X-ray 2.00A
2D1N X-ray 2.37A
2E2D X-ray 2.00A
2OW9 X-ray 1.74A
… and 37 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

Disease associations

metaphyseal chondrodysplasia, Spahr type MONDO:0009597
spondyloepimetaphyseal dysplasia, Missouri type MONDO:0011198

Drugs targeting this protein · 6

DOXYCYCLINE inhibitor
APRATASTAT inhibitor
DOXYCYCLINE CALCIUM inhibitor
DOXYCYCLINE HYCLATE inhibitor
CTS-1027 inhibitor
REBIMASTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Metalloproteinase inhibitor 1 2 shared papers
Metalloproteinase inhibitor 2 1 shared papers
Matrix metalloproteinase-9 1 shared papers
Laminin subunit alpha-1 1 shared papers
Extracellular tyrosine-protein kinase PKDCC 1 shared papers
Matrix metalloproteinase-19 1 shared papers
Extracellular tyrosine-protein kinase PKDCC 1 shared papers
Alpha-(1,6)-fucosyltransferase 1 shared papers
Interstitial collagenase 1 shared papers
Tumor necrosis factor ligand superfamily member 10 1 shared papers
Endoplasmic reticulum resident protein 29 1 shared papers
Matrix metalloproteinase-14 1 shared papers

Literature · 29 cited papers

A secreted tyrosine kinase acts in the extracellular environment. Cell · 2014
Exome sequencing reveals a nonsense mutation in MMP13 as a new cause of autosomal recessive metaphyseal anadysplasia. Eur. J. Hum. Genet. · 2015
MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type. Am. J. Med. Genet. A · 2014
Crystal structure of full-length human collagenase 3 (MMP-13) with peptides in the active site defines exosites in the catalytic domain. FASEB J. · 2013
Hydantoin based inhibitors of MMP13--discovery of AZD6605. Bioorg. Med. Chem. Lett. · 2013
Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins. J. Biol. Chem. · 2012
Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease. J. Med. Chem. · 2010
Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg. Med. Chem. Lett. · 2010
Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am. J. Hum. Genet. · 2009
Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13. J. Med. Chem. · 2009
Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J. Biol. Chem. · 2007
Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2. J. Mol. Biol. · 2007
… and 17 more in the literature graph

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