Matrix metalloproteinase-14

UniProt P50281 Organism Homo sapiens Gene MMP14 EC 3.4.24.80

Also known as: MMP14

Function

Endopeptidase that degrades various components of the extracellular matrix such as collagen. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). Activates progelatinase A/MMP2, thereby acting as a positive regulator of cell growth and migration. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a regulator of Notch signaling by mediating cleavage and inhibition of DLL1. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis. Acts as a negative regulator of the GDF15-GFRAL aversive response by mediating cleavage and inactivation of GFRAL.

Classification

Family (Pfam): PF11857 DUF3377, 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_metallopeptidase_C, Pept_M10A_Zn_BS, Peptidase_Metallo, Peptidoglycan-bd-like, PGBD-like_sf, PGBDSf
Functional cluster: Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 12

1BQQ X-ray 2.75A
1BUV X-ray 2.75A
2MQS NMR
3C7X X-ray 1.70A
3MA2 X-ray 2.05A
3X23 X-ray 2.40A
4P3C X-ray 1.94A
4P3D X-ray 1.95A
4QXU X-ray 2.30A
5H0U X-ray 2.24A
6CLZ NMR
6CM1 NMR

A predicted model is available from AlphaFold.

Gene Ontology · 48

Disease associations

Winchester syndrome MONDO:0010201

Drugs targeting this protein · 2

CTS-1027 inhibitor
REBIMASTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Matrix metalloproteinase-15 1 shared papers
Matrix metalloproteinase-14 2 shared papers
Inactive tyrosine-protein kinase 7 1 shared papers
Delta-like protein 1 1 shared papers
Matrix metalloproteinase-14 1 shared papers
Metalloproteinase inhibitor 2 1 shared papers
Nanos homolog 1 1 shared papers
72 kDa type IV collagenase 1 shared papers
Adhesion G protein-coupled receptor B1 1 shared papers
Bone marrow stromal antigen 2 1 shared papers
GDNF family receptor alpha-like 1 shared papers
Laminin subunit alpha-1 1 shared papers

Literature · 20 cited papers

Body weight regulation via MT1-MMP-mediated cleavage of GFRAL. Nat. Metab. · 2022
A secreted tyrosine kinase acts in the extracellular environment. Cell · 2014
Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. Am. J. Hum. Genet. · 2012
A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1. Oncogene · 2012
BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J. Cell. Biochem. · 2012
MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development. EMBO J. · 2011
The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J. Biol. Chem. · 2010
The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression. Oncogene · 2008
Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J. Proteome Res. · 2006
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
Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. · 2003
… and 8 more in the literature graph

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