Search
matrix metalloproteinase-2 (matrixin-2, TBE-1, 72 kD gelatinase, gelatinase A, MMP2, CLG4A)
Function:
1) substrates:
a) gelatin type 1
b) collagen-4, collagen-5, collagen-7, collagen-10
c) TGF-beta
d) fibroblast growth factor receptor 1
e) KiSS1 at a Gly-|-Leu bond
2) specifically cleaves type IV collagen (basement membrane).
3) ligand for integrin alpha-V/beta-3
5) inhibited by histatin-3 1/24 (histatin-5)
6) the propeptide is processed by MMP14 (MT-MMP1) & MMP16 (MT-MMP3)
7) cleaves the collagen-like sequence Pro-Gln-gly-|-Ile-Ala-gly-Gln
Cofactor:
- binds 4 Ca+2 per subunit
- binds 2 Zn+2 per subunit
Structure:
- conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme; dissociation of the cysteine from the Zn+2 upon the activation-peptide release activates the enzyme
- belongs to the peptidase M10A family
- contains 3 fibronectin type-II domains
- contains 4 hemopexin-like domains
Expression: produced by normal skin fibroblasts
Pathology:
- metastatic potential of transformed cells correlates with collagenase-4 activity
- defects in MMP2 are the cause of
a) multicentric osteolysis nodulosis & arthropathy
b) Winchester syndrome
Laboratory:
- matrix metallopeptidase 2 in serum
General
collagenase-4 or gelatinase
matrixin or matrix metalloproteinase
Properties
SIZE: entity length = 660 aa
MW = 74 kD
COMPARTMENT: extracellular matrix
MOTIF: signal sequence {1-29}
Cysteine switch {100-107}
MOTIF: Zn+2-binding site
SITE: 102-102
Collagenase-like 1 {110-221}
MOTIF: Ca+2-binding site
SITE: 134-134
Ca+2-binding site
SITE: 168-168
Zn+2-binding site
SITE: 178-178
Zn+2-binding site
SITE: 180-180
Ca+2-binding site
SITE: 185-185
Ca+2-binding site
SITE: 186-186
Zn+2-binding site
SITE: 193-193
Ca+2-binding site
SITE: 200-200
Ca+2-binding site
SITE: 202-202
Ca+2-binding site
SITE: 204-204
Zn+2-binding site
SITE: 206-206
Ca+2-binding site
SITE: 208-208
Ca+2-binding site
SITE: 209-209
Ca+2-binding site
SITE: 211-211
binding site
SITE: 222-396
FOR-BINDING-OF: collagen
MOTIF: fibronectin type II domain or F2 module
SITE: 228-276
FOR-BINDING-OF: collagen
MOTIF: cysteine residue {*1}
MODIFICATION: cysteine residue {*3}
cysteine residue {*2}
MODIFICATION: cysteine residue {*4}
cysteine residue {*3}
MODIFICATION: cysteine residue {*1}
cysteine residue {*4}
MODIFICATION: cysteine residue {*2}
cysteine residue {C233}
MODIFICATION: cysteine residue {C259}
cysteine residue {C247}
MODIFICATION: cysteine residue {C274}
cysteine residue {C259}
MODIFICATION: cysteine residue {C233}
cysteine residue {C274}
MODIFICATION: cysteine residue {C247}
fibronectin type II domain or F2 module
SITE: 286-334
FOR-BINDING-OF: collagen
MOTIF: cysteine residue {*1}
MODIFICATION: cysteine residue {*3}
cysteine residue {*2}
MODIFICATION: cysteine residue {*4}
cysteine residue {*3}
MODIFICATION: cysteine residue {*1}
cysteine residue {*4}
MODIFICATION: cysteine residue {*2}
cysteine residue {C291}
MODIFICATION: cysteine residue {C317}
cysteine residue {C305}
MODIFICATION: cysteine residue {C332}
cysteine residue {C317}
MODIFICATION: cysteine residue {C291}
cysteine residue {C332}
MODIFICATION: cysteine residue {C305}
fibronectin type II domain or F2 module
SITE: 344-392
FOR-BINDING-OF: collagen
MOTIF: cysteine residue {*1}
MODIFICATION: cysteine residue {*3}
cysteine residue {*2}
MODIFICATION: cysteine residue {*4}
cysteine residue {*3}
MODIFICATION: cysteine residue {*1}
cysteine residue {*4}
MODIFICATION: cysteine residue {*2}
cysteine residue {C349}
MODIFICATION: cysteine residue {C375}
cysteine residue {C363}
MODIFICATION: cysteine residue {C390}
cysteine residue {C375}
MODIFICATION: cysteine residue {C349}
cysteine residue {C390}
MODIFICATION: cysteine residue {C363}
Collagenase-like 2 {397-465}
MOTIF: Zn+2-binding site
SITE: 403-403
glutamate residue {E404}
Zn+2-binding site
SITE: 407-407
Zn+2-binding site
SITE: 413-413
cysteine residue {C469}
MODIFICATION: cysteine residue {C660}
Hemopexin-like 1 {475-518}
MOTIF: Ca+2-binding site
SITE: 476-476
Hemopexin-like 2 {520-563}
MOTIF: Ca+2-binding site
SITE: 521-521
Hemopexin-like 3 {568-615}
MOTIF: Ca+2-binding site
SITE: 569-569
N-glycosylation site {N573}
Hemopexin-like 4 {617-660}
MOTIF: Ca+2-binding site
SITE: 618-618
N-glycosylation site {N642}
cysteine residue {C660}
MODIFICATION: cysteine residue {C469}
Database Correlations
OMIM correlations
UniProt P08253
PFAM correlations
Entrez Gene 4313
Kegg hsa:4313
ENZYME 3.4.24.24
References
- UniProt :accession P08253
- Chang C, Werb Z.
The many faces of metalloproteases: cell growth, invasion,
angiogenesis and metastasis.
Trends Cell Biol. 2001 Nov;11(11):S37-43. Review.
PMID: 11684441
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/MMP2ID41396ch16q13.html