Metalloproteinase inhibitor 3 (IPR015612)

Short name: TIMP3

Overlapping homologous superfamilies

Family relationships


TIMP-3 (MEROPS identifier I35.003) is known to inhibit matrix metalloproteinases, aggrecanases, and tumour necrosis factor (TNF)-alpha-converting enzyme (TACE, ADAM17), and mutations in the Human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus dystrophy or SFD) [PMID: 9164653]. Deletion of the Mouse Timp3 gene results in an increase in TNF-alpha converting enzyme activity, constitutive release of TNF and activation of TNF signalling in the liver [PMID: 15322543]. The knockout animals also develop spontaneous air space enlargement in the lung that is evident at 2 weeks after birth and progresses with age of the animal, and succumb to death as early as 13 months of age [PMID: 11560951]. TIMP-3 has been shown to regulate agonist-induced vascular remodelling and hypertension [PMID: 23524300].

Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs) found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the extracellular matrix (ECM). The balance between MMPs and TIMPs activities is involved in both normal and pathological events such as wound healing, tissue remodeling, angiogenesis, invasion, tumourigenesis and metastasis [PMID: 15036259]. TIMPs also exhibit functions that appear to be independent of their metalloproteinase inhibitory capacity [PMID: 15036259]. There are four mammalian TIMPs (TIMP-1 to -4), and each TIMP has its own profile of metalloproteinase inhibition.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0008191 metalloendopeptidase inhibitor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.