Matrix metallopeptidase 13

Collagenase 3 is an enzyme that in humans is encoded by the MMP13 gene.^[5][6] It is a member of the matrix metalloproteinase (MMP) family. Like most MMPs, it is secreted as an inactive pro-form.^[7] MMP-13 has a predicted molecular weight around 54 kDa.^[8] It is activated once the pro-domain is cleaved, leaving an active enzyme composed of the catalytic domain and the hemopexin-like domain PDB: 1PEX​. Although the actual mechanism has not been described, the hemopexin domain participates in collagen degradation, the catalytic domain alone being particularly inefficient in collagen degradation. During embryonic development, MMP-13 is expressed in the skeleton as required for restructuring the collagen matrix for bone mineralization. In pathological situations it is highly overexpressed; this occurs in human carcinomas, rheumatoid arthritis and osteoarthritis.^[9]

MMP13
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EUB, 1FLS, 1FM1, 1PEX, 1XUC, 1XUD, 1XUR, 1YOU, 1ZTQ, 2D1N, 2E2D, 2OW9, 2OZR, 2PJT, 2YIG, 3ELM, 3I7G, 3I7I, 3KEC, 3KEJ, 3KEK, 3KRY, 3LJZ, 3O2X, 3TVC, 3WV1, 3WV2, 3WV3, 3ZXH, 456C, 4A7B, 4FU4, 4FVL, 4G0D, 4JP4, 4JPA, 4L19, 5BOT, 5BOY, 5BPA, 830C
Identifiers
Aliases	MMP13, CLG3, MANDP1, MMP-13, Matrix metallopeptidase 13, MDST
External IDs	OMIM: 600108; MGI: 1340026; HomoloGene: 20548; GeneCards: MMP13; OMA:MMP13 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q22.2 Start 102,942,995 bp[1] End 102,955,732 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A1 Start 7,272,514 bp[2] End 7,283,331 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber cartilage tissue tibia mucosa of paranasal sinus trabecular bone buccal mucosa cell gonad Achilles tendon olfactory zone of nasal mucosa gums Top expressed in body of femur calvaria tibiofemoral joint stroma of bone marrow olfactory epithelium molar ankle fossa lumbar spinal ganglion epiphysis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function collagen binding zinc ion binding metal ion binding peptidase activity metalloendopeptidase activity hydrolase activity metallopeptidase activity serine-type endopeptidase activity calcium ion binding Cellular component extracellular matrix extracellular region extracellular space Biological process growth plate cartilage development bone mineralization bone morphogenesis extracellular matrix disassembly endochondral ossification proteolysis cartilage development collagen catabolic process extracellular matrix organization response to amyloid-beta Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4322 17386 Ensembl ENSG00000137745 ENSMUSG00000050578 UniProt P45452 P33435 RefSeq (mRNA) NM_002427 NM_008607 RefSeq (protein) NP_002418 NP_032633 Location (UCSC) Chr 11: 102.94 – 102.96 Mb Chr 9: 7.27 – 7.28 Mb PubMed search [3] [4]
Wikidata
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Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene cleaves type II collagen more efficiently than types I and III^{[citation needed]}. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.^[6]

Regulation

Transcriptional regulation of MMP-13 is tightly controlled due to its potent proteolytic capacity. There are several binding domains for various transcription factors including AP-1, PEA-3 and OSE-2 as well as a sequence with homology to a TGF-β inhibitory element (TIE). Moreover, several cytokines and growth factors have been demonstrated to affect Mmp13 gene expression, including parathyroid hormone, IGF-1, TGF-β, hepatocyte growth factor and many inflammatory cytokines such as IL-1α and IL-1β.^[10]

The upstream regulatory region of the Mmp13 gene contains a number of transcription factor binding sites but it was recently discovered that there is a conserved forkhead response element (FHRE) consensus sequence for FOXO3a in the human, mouse and rat Mmp13 promoter. Endogenous FOXO3a activation results in marked upregulation of Mmp13 expression which is capable of promoting extracellular matrix degradation and apoptotic cell death. ^[11]

Clinical Relevance

MMP-13 has long been a protein of interest in the context of osteoarthritis and rheumatoid arthritis.^[12]

The role of MMP-13 has also been thoroughly examined in atherosclerosis, specifically in potentially reducing the collagen content of the fibrous cap. ^{[13] [14] [15] [16] [17]}