ID:MMP2_HUMAN DESCRIPTION: RecName: Full=72 kDa type IV collagenase; EC=3.4.24.24; AltName: Full=72 kDa gelatinase; AltName: Full=Gelatinase A; AltName: Full=Matrix metalloproteinase-2; Short=MMP-2; AltName: Full=TBE-1; Contains: RecName: Full=PEX; Flags: Precursor; 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. FUNCTION: 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. 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: Binds 4 calcium ions per subunit. COFACTOR: Binds 2 zinc ions per subunit. ENZYME REGULATION: Inhibited by histatin-3 1/24 (histatin-5). SUBUNIT: Interacts (via the C-terminal hemopexin-like domains- containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B. INTERACTION: Q8IX30:SCUBE3; NbExp=2; IntAct=EBI-1033518, EBI-4479975; SUBCELLULAR LOCATION: 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. TISSUE SPECIFICITY: Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. INDUCTION: Aspirin appears to inhibit expression. 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. PTM: Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. PTM: The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT- MMP3). Autocatalytic cleavage in the C-terminal produces the anti- angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3. DISEASE: Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:259600]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg- Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes. SIMILARITY: Belongs to the peptidase M10A family. SIMILARITY: Contains 3 fibronectin type-II domains. SIMILARITY: Contains 4 hemopexin-like domains. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MMP2ID41396ch16q13.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P08253
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AL832088 - Homo sapiens mRNA; cDNA DKFZp313D1831 (from clone DKFZp313D1831). LF208225 - JP 2014500723-A/15728: Polycomb-Associated Non-Coding RNAs. LF213753 - JP 2014500723-A/21256: Polycomb-Associated Non-Coding RNAs. X58968 - H.sapiens RNA for 5` sequence of type IV collagenase. JD555263 - Sequence 536287 from Patent EP1572962. AK312711 - Homo sapiens cDNA, FLJ93112, highly similar to Homo sapiens matrix metalloproteinase 2 (gelatinase A, 72kDagelatinase, 72kDa type IV collagenase) (MMP2), mRNA. JD521329 - Sequence 502353 from Patent EP1572962. BC002576 - Homo sapiens matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase), mRNA (cDNA clone MGC:2313 IMAGE:3161383), complete cds. JC506674 - Sequence 42 from Patent EP2733220. JC737786 - Sequence 42 from Patent WO2014075939. JC506688 - Sequence 56 from Patent EP2733220. JC737800 - Sequence 56 from Patent WO2014075939. LF373563 - JP 2014500723-A/181066: Polycomb-Associated Non-Coding RNAs. JD484885 - Sequence 465909 from Patent EP1572962. DQ891952 - Synthetic construct clone IMAGE:100004582; FLH181717.01X; RZPDo839G05136D matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) (MMP2) gene, encodes complete protein. DQ895138 - Synthetic construct Homo sapiens clone IMAGE:100009598; FLH181713.01L; RZPDo839G05135D matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) (MMP2) gene, encodes complete protein. CU678050 - Synthetic construct Homo sapiens gateway clone IMAGE:100017762 5' read MMP2 mRNA. AB385158 - Synthetic construct DNA, clone: pF1KB5697, Homo sapiens MMP2 gene for 72 kDa type IV collagenase precursor, complete cds, without stop codon, in Flexi system. KJ897194 - Synthetic construct Homo sapiens clone ccsbBroadEn_06588 MMP2 gene, encodes complete protein. KR710612 - Synthetic construct Homo sapiens clone CCSBHm_00014648 MMP2 (MMP2) mRNA, encodes complete protein. KR710613 - Synthetic construct Homo sapiens clone CCSBHm_00014650 MMP2 (MMP2) mRNA, encodes complete protein. J03210 - Human collagenase type IV mRNA, 3' end. AK301536 - Homo sapiens cDNA FLJ59773 complete cds, highly similar to 72 kDa type IV collagenase precursor (EC 3.4.24.24). AK310314 - Homo sapiens cDNA, FLJ17356. LF373566 - JP 2014500723-A/181069: Polycomb-Associated Non-Coding RNAs. LF373569 - JP 2014500723-A/181072: Polycomb-Associated Non-Coding RNAs. LF373570 - JP 2014500723-A/181073: Polycomb-Associated Non-Coding RNAs. LF373571 - JP 2014500723-A/181074: Polycomb-Associated Non-Coding RNAs. AK057680 - Homo sapiens cDNA FLJ33118 fis, clone TRACH2001347, moderately similar to 72 KDA TYPE IV COLLAGENASE PRECURSOR (EC 3.4.24.24). DQ385623 - Homo sapiens MMP2 mRNA, partial cds. LF373573 - JP 2014500723-A/181076: Polycomb-Associated Non-Coding RNAs. LF373577 - JP 2014500723-A/181080: Polycomb-Associated Non-Coding RNAs. LF373581 - JP 2014500723-A/181084: Polycomb-Associated Non-Coding RNAs. LF373582 - JP 2014500723-A/181085: Polycomb-Associated Non-Coding RNAs. LF373584 - JP 2014500723-A/181087: Polycomb-Associated Non-Coding RNAs. LF373586 - JP 2014500723-A/181089: Polycomb-Associated Non-Coding RNAs. LF373587 - JP 2014500723-A/181090: Polycomb-Associated Non-Coding RNAs. JD159339 - Sequence 140363 from Patent EP1572962. JD062582 - Sequence 43606 from Patent EP1572962. JD160394 - Sequence 141418 from Patent EP1572962. JD307431 - Sequence 288455 from Patent EP1572962. JD479775 - Sequence 460799 from Patent EP1572962. JD290209 - Sequence 271233 from Patent EP1572962. JD497692 - Sequence 478716 from Patent EP1572962. JD306586 - Sequence 287610 from Patent EP1572962. JD334266 - Sequence 315290 from Patent EP1572962. JD318382 - Sequence 299406 from Patent EP1572962. LF373590 - JP 2014500723-A/181093: Polycomb-Associated Non-Coding RNAs. JD269204 - Sequence 250228 from Patent EP1572962. LF373592 - JP 2014500723-A/181095: Polycomb-Associated Non-Coding RNAs. JD463431 - Sequence 444455 from Patent EP1572962. MA609140 - JP 2018138019-A/181066: Polycomb-Associated Non-Coding RNAs. MA443802 - JP 2018138019-A/15728: Polycomb-Associated Non-Coding RNAs. MA449330 - JP 2018138019-A/21256: Polycomb-Associated Non-Coding RNAs. MA609143 - JP 2018138019-A/181069: Polycomb-Associated Non-Coding RNAs. MA609146 - JP 2018138019-A/181072: Polycomb-Associated Non-Coding RNAs. MA609147 - JP 2018138019-A/181073: Polycomb-Associated Non-Coding RNAs. MA609148 - JP 2018138019-A/181074: Polycomb-Associated Non-Coding RNAs. MA609150 - JP 2018138019-A/181076: Polycomb-Associated Non-Coding RNAs. MA609154 - JP 2018138019-A/181080: Polycomb-Associated Non-Coding RNAs. MA609158 - JP 2018138019-A/181084: Polycomb-Associated Non-Coding RNAs. MA609159 - JP 2018138019-A/181085: Polycomb-Associated Non-Coding RNAs. MA609161 - JP 2018138019-A/181087: Polycomb-Associated Non-Coding RNAs. MA609163 - JP 2018138019-A/181089: Polycomb-Associated Non-Coding RNAs. MA609164 - JP 2018138019-A/181090: Polycomb-Associated Non-Coding RNAs. MA609167 - JP 2018138019-A/181093: Polycomb-Associated Non-Coding RNAs. MA609169 - JP 2018138019-A/181095: Polycomb-Associated Non-Coding RNAs. MP015277 - Sequence 480 from Patent WO2019016252.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_reckPathway - Inhibition of Matrix Metalloproteinases
Reactome (by CSHL, EBI, and GO)
Protein P08253 (Reactome details) participates in the following event(s):
R-HSA-1592278 Autocatalytic activation of proMMP2 R-HSA-1604359 Initial activation of proMMP2 by MMP1, 7 R-HSA-1604360 Initial activation of proMMP2 by MMP14 R-HSA-1604350 MMP14:TIMP2 binds proMMP2 R-HSA-1604368 Autocatalytic activation of bound proMMP2 R-HSA-1454791 MMP2, MMP7, MMP9 bind CD44 R-HSA-1454781 MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin R-HSA-8940554 MMP2 cleaves OPTC R-HSA-381435 Matrix metalloproteinase proteolyzes IGF:IGFBP3:ALS R-HSA-1564143 Collagen type X degradation by MMP1,2 R-NUL-2484869 Collagen type X degradation by MMP1,2 R-HSA-1592297 Full activation of MMP1 R-HSA-1454822 Collagen type I degradation by MMP1,2,8,13, PRSS2 R-HSA-1564142 Collagen type IV degradation by MMP2,3,4,9,10,12 R-HSA-1564164 Collagen type V degradation by MMP2,9,10 R-HSA-1564112 Collagen type VI degradation by MMP2,9,11 R-HSA-1564120 Collagen type VII degradation by MMP1,2,3 R-HSA-1564179 Collagen type XI degradation by MMP1,2,3,9 R-NUL-2484859 Collagen type XI degradation by MMP1,2,3,9 R-HSA-2485148 Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13 R-HSA-1566962 Elastin degradation by elastin-degrading extracellular proteinases R-HSA-2534248 DCN (decorin) degradation by MMP2, MMP3, MMP7 R-HSA-3791149 Brevican degradation by MMP1, 2, 3, 7,8,10,13,19 R-HSA-3791295 Aggrecan degradation by MMP1,2,3,7,9,12,13 R-NUL-3814821 Aggrecan degradation by MMP1,2,3,7,9,12,13 R-HSA-8943959 MMP2, MMP9 cleave SCUBE3 R-HSA-1592436 Initial activation of proMMP9 by MMPs R-HSA-1604690 Activation of MMP9 intermediate form by MMPs R-HSA-1566979 Laminin-332 degradation by laminin-322 degrading extracellular proteinases R-HSA-1592389 Activation of Matrix Metalloproteinases R-HSA-1474228 Degradation of the extracellular matrix R-HSA-6785807 Interleukin-4 and 13 signaling R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-1442490 Collagen degradation R-HSA-1474244 Extracellular matrix organization R-HSA-3928665 EPH-ephrin mediated repulsion of cells R-HSA-449147 Signaling by Interleukins R-HSA-392499 Metabolism of proteins R-HSA-2682334 EPH-Ephrin signaling R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-422475 Axon guidance R-HSA-168256 Immune System R-HSA-1266738 Developmental Biology
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
