TIMP1

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Protein-coding gene in the species Homo sapiens

title: "TIMP1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/TIMP1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a two-domain glycoprotein with a molecular weight of 28 kDa. TIMP1 is expressed in several tissues of organisms.

This protein is a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. 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) through binding of the TIMP1 N-terminal domain to the metalloproteinase active site. It has also been suggested that the C-terminal domain of TIMP1 can bind to the inactive precursors pro-MMP-2 and pro-MMP-9. 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 inflammation, cancer, and fibrosis. 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.

Cell-surface receptor binding

While traditionally reported for its protease-inhibiting ability, the C-terminal domain of TIMP1 has been shown to bind to cell-surface receptors including the tetraspanins CD63 and CD82. These interactions can activate downstream signaling pathways including the MAPK pathway.

Other names

  • Erythroid potentiating activity (EPA)
  • Human collagenase inhibitor (HCI)

Regulation of TIMP expression

Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I 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

References

  1. (2004-10-01). "TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells". Kidney International.
  2. (January 2010). "The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.
  3. (1997-11-21). "Kinetic Analysis of the Binding of Human Matrix Metalloproteinase-2 and -9 to Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2*". The Journal of Biological Chemistry.
  4. (March 2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.
  5. (August 1991). "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology.
  6. (May 1997). "Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene". Biology of Reproduction.
  7. (September 2000). "Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice". Biology of Reproduction.
  8. (May 2023). "Cut loose TIMP-1: an emerging cytokine in inflammation". Trends in Cell Biology.
  9. (June 2017). "Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63–Integrin β1 Interaction". Hypertension.
  10. (Nov 2012). "Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression". BMB Reports.
  11. (August 1991). "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology.
  12. (December 2015). "Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine". Reproductive Biology and Endocrinology.
  13. (2013-10-15). "TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression". PLOS ONE.
  14. (November 2005). "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory". The European Journal of Neuroscience.
  15. (August 1991). "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology.
  16. (2006-08-17). "Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein". The EMBO Journal.
  17. (March 2006). "Novel functions of TIMPs in cell signaling". Cancer and Metastasis Reviews.
  18. "Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1".
  19. (February 2004). "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells". Molecular and Cellular Endocrinology.
  20. (Dec 2013). "Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma". International Journal of Clinical and Experimental Pathology.
  21. (January 2014). "A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma". Journal of Translational Medicine.

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