Stromelysin-1

UniProt P08254 Organism Homo sapiens Gene MMP3, STMY1 EC 3.4.24.17

Also known as: MMP3, STMY1

Function

Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Also acts intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage. In addition, plays a role in immune response and possesses antiviral activity against various viruses such as vesicular stomatitis virus, influenza A virus (H1N1) and human herpes virus 1. Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities.

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 · 44

1B3D X-ray 2.30A
1B8Y X-ray 2.00A
1BIW X-ray 2.50A
1BM6 NMR
1BQO X-ray 2.30A
1C3I X-ray 1.83A
1C8T X-ray 2.60A
1CAQ X-ray 1.80A
1CIZ X-ray 1.64A
1CQR X-ray 2.00A
1D5J X-ray 2.60A
1D7X X-ray 2.00A
… and 32 more

A predicted model is available from AlphaFold.

Gene Ontology · 27

Disease associations

coronary heart disease, susceptibility to, 6 MONDO:0013765

Drugs targeting this protein · 2

MARIMASTAT inhibitor
CTS-1027 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Stromelysin-1 1 shared papers
Stromelysin-1 1 shared papers
Metalloproteinase inhibitor 1 1 shared papers
Interstitial collagenase 1 shared papers
Matrix metalloproteinase-9 1 shared papers

Literature · 23 cited papers

Matrix metalloproteinase 3 restricts viral infection by enhancing host antiviral immunity. Antiviral Res. · 2022
Matrix metalloproteinase-3 is activated by HtrA2/Omi in dopaminergic cells: relevance to Parkinson's disease. Neurochem. Int. · 2012
Role of matrix metalloproteinase 3-mediated alpha-synuclein cleavage in dopaminergic cell death. J. Biol. Chem. · 2011
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N. Engl. J. Med. · 2002
Prostromelysin-1 (proMMP-3) stimulates plasminogen activation by tissue-type plasminogen activator. Eur. J. Biochem. · 2000
Crystal structure of the stromelysin catalytic domain at 2.0-A resolution: inhibitor-induced conformational changes. J. Mol. Biol. · 1999
X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity. Protein Sci. · 1999
Solution structures of stromelysin complexed to thiadiazole inhibitors. Protein Sci. · 1998
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity. Protein Sci. · 1998
Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor. Biochemistry · 1998
… and 11 more in the literature graph

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