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Domain

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Function

Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). 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 (PubMed:22065321, PubMed:8015608). Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657, PubMed:22065321). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a regulator of Notch signaling by mediating cleavage and inhibition of DLL1 (PubMed:21572390). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (PubMed:22330140). Acts as a negative regulator of the GDF15-GFRAL aversive response by mediating cleavage and inactivation of GFRAL (PubMed:35177851).

Involvement in disease

Winchester syndrome

WNCHRS

A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The precursor is cleaved by a furin endopeptidase.

Tyrosine phosphorylated by PKDCC/VLK.

Sequence similarities

Belongs to the peptidase M10A family.

Tissue specificity

Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors.

Cellular localization

  • Cell membrane
  • Single-pass type I membrane protein
  • Melanosome
  • Cytoplasm
  • Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065). Forms a complex with BST2 and localizes to the cytoplasm (PubMed:17081065).

Alternative names

Matrix metalloproteinase-14, MMP-14, MMP-X1, Membrane-type matrix metalloproteinase 1, Membrane-type-1 matrix metalloproteinase, MT-MMP 1, MTMMP1, MT1-MMP, MT1MMP, MMP14

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

65894Da

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Primary Antibodies

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Target