TIMP metallopeptidase inhibitor 1, also known as TIMP1, a

tissue inhibitor of metalloproteinases Tissue inhibitors of metalloproteinases (TIMPs) are specific endogenous protease inhibitors to the matrix metalloproteinases. There are four TIMPs; '' TIMP1'', ''TIMP2'', ''TIMP3'' and '' TIMP4''. TIMP3 has been observed progressively downregulated ...

, 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 Tissue inhibitors of metalloproteinases (TIMPs) are specific endogenous protease inhibitors to the matrix metalloproteinases. There are four TIMPs; ''TIMP1'', '' TIMP2'', '' TIMP3'' and ''TIMP4''. TIMP3 has been observed progressively downregulate ...

. The glycoprotein is a natural inhibitor 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 s ...

. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

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 Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

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 autocrin ...

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 require ...

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 sex ...

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, cultu ...

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 ...

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. Synaps ...

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 or melanoma.

References

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 inhibit ...

online database for peptidases and their inhibitors
I35.001
* {{gene-X-stub

Function

Other names

Regulation of TIMP expression

See also

References

Further reading

External links