Names & Taxonomy
- Uniprot ID:
- P08253
- Entry Name:
- MMP2_HUMAN
- Status:
- reviewed
- Protein Names:
- 72 kDa type IV collagenase (EC 3.4.24.24) (72 kDa gelatinase) (Gelatinase A) (Matrix metalloproteinase-2) (MMP-2) (TBE-1) [Cleaved into: PEX]
- Gene Names:
- MMP2 CLG4A
- Gene Names Primary:
- MMP2
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 660
- Sequence:
- MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGCPKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWDKNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGDGYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFNGKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGTSYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKYESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGALMAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQIRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEYWIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDPGFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Isoform 1: Secreted, extracellular space, extracellular matrix. Membrane. Nucleus. Note=Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes.; Isoform 2: Cytoplasm. Mitochondrion.
Function
- Function:
- Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
- Catalytic Activity:
- Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.
- Cofactor:
- COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; ; Note=Binds 4 Ca(2+) ions per subunit.;; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; ; Note=Binds 2 Zn(2+) ions per subunit.;
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited by histatin-3 1/24 (histatin-5).
- Active Site:
- ACT_SITE 404 404
- Cross Reference Drug Bank:
- DB01197 DB00786
- Gene Ontology Go:
- extracellular region
extracellular space
mitochondrion
nucleus
plasma membrane
proteinaceous extracellular matrix
sarcomere
metalloendopeptidase activity
metallopeptidase activity
serine-type endopeptidase activity
zinc ion binding
angiogenesis
axon guidance
blood vessel maturation
bone trabecula formation
cellular protein metabolic process
cellular response to amino acid stimulus
collagen catabolic process
embryo implantation
endodermal cell differentiation
ephrin receptor signaling pathway
extracellular matrix disassembly
extracellular matrix organization
face morphogenesis
intramembranous ossification
positive regulation of innate immune response
proteolysis
response to hypoxia - Gene Ontology Biological Process:
- angiogenesis
axon guidance
blood vessel maturation
bone trabecula formation
cellular protein metabolic process
cellular response to amino acid stimulus
collagen catabolic process
embryo implantation
endodermal cell differentiation
ephrin receptor signaling pathway
extracellular matrix disassembly
extracellular matrix organization
face morphogenesis
intramembranous ossification
positive regulation of innate immune response
proteolysis
response to hypoxia - Gene Ontology Molecular Function:
- metalloendopeptidase activity
metallopeptidase activity
serine-type endopeptidase activity
zinc ion binding - Gene Ontology Cellular Component:
- extracellular region
extracellular space
mitochondrion
nucleus
plasma membrane
proteinaceous extracellular matrix
sarcomere - Keywords:
- 3D-structure
Alternative splicing
Angiogenesis
Autocatalytic cleavage
Calcium
Collagen degradation
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Extracellular matrix
Glycoprotein
Hydrolase
Membrane
Metal-binding
Metalloprotease
Mitochondrion
Nucleus
Phosphoprotein
Polymorphism
Protease
Reference proteome
Repeat
Secreted
Signal
Zinc
Zymogen - Interacts With:
- Q8NBP7; Q8IX30
Publication
- PubMed ID:
- 2162831 1851724 14702039 15616553 15489334 2158484 2834383 1480041 1655733 8646777 9119036 9476898 10559137 11029402 11751392 11179305 11710594 12714657 12879005 14766804 17435175 19493954 18971601 22905912 22509276 7583664 8549817 10356396 10545322 11320090 12147339 11928808 12032297 16392792 11431697 15691365 16542393 16959974