Tissue inhibitors of metalloproteinases (TIMPs) are specific endogenous protease inhibitors to the
matrix metalloproteinase
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs b ...
s. There are four TIMPs; ''
TIMP1
TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein with a molecular weight of 28 kDa. TIMP1 is expressed from several tissues of organisms.
This protein is a member of the TIMP fami ...
'', ''
TIMP2
Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.
Function
The proteins encoded by this gene family are n ...
'', ''
TIMP3
Metalloproteinase inhibitor 3 is a protein that in humans is encoded by the ''TIMP3'' gene.
This gene belongs to the tissue inhibitor of metalloproteinases gene family. The proteins encoded by this gene family are inhibitors of the matrix metall ...
'' and ''
TIMP4
Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the ''TIMP4'' gene.
This gene belongs to the tissue inhibitor of metalloproteinases gene family. The proteins encoded by this gene family are inhibitors of the matrix metallop ...
''.
TIMP3 has been observed progressively downregulated in
Human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
-positive
neoplastic keratinocytes derived from uterine cervical
preneoplastic lesions at different levels of malignancy.
For this reason, TIMP3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical
preneoplastic lesions progression.
Overall, all
MMPs are inhibited by TIMPs once they are activated but the
gelatinase Gelatinases are enzymes capable of degrading gelatin.
Gelatinases are expressed in several bacteria including ''Pseudomonas aeruginosa'' and ''Serratia marcescens''.
In humans, the gelatinases are matrix metalloproteinases MMP2 and MMP9
Matrix ...
s (
MMP-2
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the ''MMP2'' gene. The ''MMP2'' gene is located on chromosome 16 at position 12.2.
Function
Proteins of the ...
and
MMP-9
Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extracel ...
) can form complexes with TIMPs when the enzymes are in the latent form.
The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP (
MMP-14), a membrane-anchored MMP.
The role of the pro-MMP-9/TIMP-1 complex is still unknown.
References
*
External links
*{{Commonscat-inline, Tissue inhibitor of metalloproteinases, TIMP
Human proteins