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 family. The
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...
is a natural
inhibitor
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
of 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 be ...
s (MMPs), a group of peptidases involved in degradation of the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...
. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote
cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.
Function
TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs). In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing, and pregnancy.
The dysregulated activity of TIMP1 has been implicated in cancer.
In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium. Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy. Studies attribute this role to a mechanism involving the chromatin structure at the TIMP1 promoter region, implicating new pharmaceutical possibilities for the therapeutic regulation of TIMP1. Accordingly, TIMP1 can be manipulated ''in vitro'' using techniques, like the TIMP1 knock-out.
Other names
* Erythroid potentiating activity (EPA)
* Human collagenase inhibitor (HCI)
Regulation of TIMP expression
Transcription of this
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
is highly inducible in response to many
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
s and
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s. In addition, the expression from some but not all inactive
X chromosome
The X chromosome is one of the two sex-determining chromosomes ( allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO se ...
s suggests that this gene inactivation is polymorphic in
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
female
Female (symbol: ♀) is the sex of an organism that produces the large non-motile ova (egg cells), the type of gamete (sex cell) that fuses with the male gamete during sexual reproduction.
A female has larger gametes than a male. Females a ...
s. This gene is located within intron 6 of the
synapsin I
Synapsin I, is the collective name for Synapsin Ia and Synapsin Ib, two nearly identical phosphoproteins that in humans are encoded by the ''SYN1'' gene. In its phosphorylated form, Synapsin I may also be referred to as phosphosynaspin I. Synap ...
gene and is transcribed in the opposite direction.
In adrenocortical cells the trophic hormone ACTH induces expression of TIMP-1 and the increase in TIMP expression is also associated with decreased collagenase activity.
Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such as
laryngeal carcinoma
Laryngeal cancers are mostly squamous-cell carcinomas, reflecting their origin from the epithelium of the larynx.
Cancer can develop in any part of the larynx. The prognosis is affected by the location of the tumour. For the purposes of staging, ...
or
melanoma.
See also
*
TIMP2,
TIMP3,
TIMP4
References
Further reading
*
*
External links
* The
MEROPS
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibi ...
online database for peptidases and their inhibitors
I35.001*
{{gene-X-stub