InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MMP2

Summary

InnateDB Protein

IDBP-31273.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MMP2

Protein Name

matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)

Synonyms

CLG4; CLG4A; MMP-II; MONA; TBE-1;

Species

Homo sapiens

Ensembl Protein

ENSP00000219070

InnateDB Gene

IDBG-31271 (MMP2)

Protein Structure

UniProt Annotation

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.

Subcellular Localization

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.

Disease Associations

Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. {ECO:0000269PubMed:11431697, ECO:0000269PubMed:15691365, ECO:0000269PubMed:16542393}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. {ECO:0000269PubMed:11751392}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	31 [view]
Protein-Protein	29 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004222	metalloendopeptidase activity
GO:0004252	serine-type endopeptidase activity
GO:0005515	protein binding
GO:0008237	metallopeptidase activity
GO:0008270	zinc ion binding

Biological Process

GO:0001525	angiogenesis
GO:0001666	response to hypoxia
GO:0001955	blood vessel maturation
GO:0001957	intramembranous ossification
GO:0006508	proteolysis
GO:0007566	embryo implantation
GO:0022617	extracellular matrix disassembly
GO:0030198	extracellular matrix organization
GO:0030574	collagen catabolic process
GO:0044267	cellular protein metabolic process
GO:0045089	positive regulation of innate immune response
GO:0048705	skeletal system morphogenesis
GO:0060325	face morphogenesis
GO:0060346	bone trabecula formation
GO:0071230	cellular response to amino acid stimulus

Cellular Component

GO:0005576	extracellular region
GO:0005578	proteinaceous extracellular matrix
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005886	plasma membrane
GO:0030017	sarcomere
GO:0031012	extracellular matrix

Protein Structure and Domains

PDB ID

InterPro

IPR000562 Fibronectin, type II, collagen-binding
IPR000585 Hemopexin-like domain
IPR001818 Peptidase M10, metallopeptidase
IPR002477 Peptidoglycan binding-like
IPR006026 Peptidase, metallopeptidase
IPR013806 Kringle-like fold
IPR018487 Hemopexin-like repeats
IPR021190 Peptidase M10A

PFAM

PF00040
PF00413
PF01471
PF00045

PRINTS

PR00138

PIRSF

SMART

SM00059
SM00235
SM00120

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt