This website uses cookies to ensure you get the best experience on our website.
- Table of Contents
3 Citations 5 Q&As
Facts about Metalloproteinase inhibitor 4.
.
Human | |
---|---|
Gene Name: | TIMP4 |
Uniprot: | Q99727 |
Entrez: | 7079 |
Belongs to: |
---|
protease inhibitor I35 (TIMP) family |
metalloproteinase inhibitor 4; TIMP metallopeptidase inhibitor 4; TIMP4; TIMP-4; tissue inhibitor of metalloproteinase 4; Tissue inhibitor of metalloproteinases 4
Mass (kDA):
25.503 kDA
Human | |
---|---|
Location: | 3p25.2 |
Sequence: | 3; NC_000003.12 (12153068..12158912, complement) |
Abundant in heart and present at low levels in many other tissues.
Secreted.
TIMP4 is an immunoreactive marker that can be found in many animal tissues. There are several biological tests that use antibodies to detect TIMP4. These antibodies can be monoclonal or multiclonal and react to TIMP4 from many different samples. Boster Bio has produced antibodies for TIMP4 in rabbit and mouse. We will be discussing methods for purifying these polypeptides and determining their functional activity.
The company has created a blocker peptide to prevent the activity TIMP-4, a metaloproteinase. The polypeptide, a natural molecule, can be found in a variety of tissues. The target of this compound is the TIMP-4 protein, which inhibits the activity of matrix metalloproteinases. These peptidases help to remove extracellular mater. TIMP-4 is a secreted protein that has many functions, including platelet aggregation as well as hormone regulation. It may also play a significant role in endometrial tissue remodelling.
The polypeptide was produced using a proprietary method, which is based in an adenoviral virus that expresses TIMP-4. The sequence of this polypeptide is shown in FIGS. FIGS. These figures show deduced amino acids sequence and cDNA clone maps. These three figures give you a more detailed look at the process of synthesizing human TIMP-4.
The present invention provides a method for obtaining polypeptides containing deleted amino acid residues. These polypeptides can be described by the general formula 1-n. Here, n is an integer from 2 to 6 and corresponds the position the amino acid in FIGS. 1A (and 1B) respectively. The polypeptides in the present invention exhibit biological activity and may have an activity to inhibit metalloproteinases.
The TIMP-4 polypeptide mutated contains more than 95% the human TIMP-4 sequence. These mutated TIMP-4 protein retain many functions similar to the mature TIMP-4 peptide. These products could be useful in diagnostic or therapeutic applications. What is the difference of TIMP-4 mutein versus a modified copy? Read on to find out.
The genetic engineering of a host cell with human TIMP-4 DNA sequence is the key to producing the polypeptide. This is just like any other recombinant technology. These cells are then maintained in normal conditions under normal conditions in nutrient media. This allows the production of the polypeptide and its recovery. The protein obtained is then used in different applications. The product credits are valid for scientists worldwide.
The TIMP-4 family of polypeptides are designed to have one or more amino acid residues deleted from the carboxy terminus. These TIMP-4 polypeptides are shown in FIG. 1 and SEQID NO.2. A polypeptide with one or more residues deleted from the carboxy terminus is defined by a general formula, m-224, where m is an integer from two to twenty-four, which corresponds to the position of an amino acid residue in FIGS. 1A-B.
Polypeptides with one deletion or more can still retain their immunologic ability. It is possible to determine whether such peptides retain their immunologic activities by molecular analysis. In the present invention, human TIMP-4 polypeptides with one or more residues deleted from the carboxy terminus may exhibit immunological activity. They are also designed to retain their biological activity in a variety cells, including the immune.
Alternately, the polypeptides can also contain an epitope that contains amino acid sequences with SEQ ID No.2 plus 29. These polypeptides exhibit a high level of identity (80%), which is higher that the average of ninety seven percent polypeptides. These polypeptides may also include sequences containing other amino acids than the one mentioned above.
The present invention reveals a method to produce fusion proteins using a foreign polypeptide that contains a DNA sequence. These polypeptides contain an N-terminal identification peptide to confer desired characteristics to the recombinant protein. These proteins are capable of stabilizing and simplifying purification of the expressed recombinant product.
TIMP-4 polypeptides can be created from human DNA using a patented process. The result is highly purified TIMP-4. The process also allows for modifying the sequence of existing human TIMP-4 to produce a variant that is 95% identical to the original polypeptide. Modification allows residues to be added, deleted, or substituted in the reference sequence at different positions. The modifications can be made at the amino or carboxy terminus. They may also be interspersed with other groups of residues.
The method could also include polynucleotide-encoding regions for mature proteins. The polynucleotide can contain a sequence of nucleotides encoding non-coding elements. Polynucleotides with leader sequences are also known as preproteins. These polypeptides may be called preproteins. In order to produce mature protein, host cells must cleave the leader sequences.
TIMPs are regulatory proteins that inhibit metalloproteinases. They regulate multiple cellular molecules and extracellular space. Their multiple functions in a range of diseases suggests they could be therapeutic agents. Currently, this protein is only available from the bloodstream. A future study might show that this protein can be stimulated to produce therapeutic effects.
MMPs have many structural aspects and biochemical properties, including substrate specificity (TIMP2) and TIMP inhibition. The structure of the proMMP-2-TIMP2 complex is a step in gaining knowledge about how the enzymes assemble, and it is essential to investigate their role during cell migration. The collagenase was the first member of the MMP family. Collagenase cleaves triple-helical collagen.
The crystal structure shows that the C terminal domain of the TIMP-2 protein interacts directly with the blades (DGAL) of the hemopexin. The N-terminal inhibitory region of TIMP-2 is also free to interact with other MMPs. These interactions are a mechanism of TIMP-2's action. In the meantime we have learned more information about this protein.
Cleavage of the propeptidedomain is an important step in proteinase-mediated TIMP-4 degradation. This is achieved through the activation of another MMP, which cleaves the bait area. After cleavage of this bait region, a tenth MMP is activated to complete the removal of propeptide. These enzymes can then cleave a single propeptide.
MMPs become active when proteinases are stimulated. However, the activation of MMPs in vitro can also be accomplished by chemical agents. The most common of these are thiol-modifying agents such as 4-aminophenylmercuric acetate, HgCl2, and N-ethylmaleimide. Reactive oxygen agents, such as chaotropic agents, can be utilized for MMP activation. MMPs are also activated by heat treatment or low pH.
TIMPs include 184-194 amino acids. The N terminal domain folds independent and is associated with three disulfide bonds. The C-terminal domain possesses anti-MMP activity. While TIMP-1 and TIMP-3 are poor inhibitors of MT1-MMP, they inhibit ADAMs, such as MMP-10.
Polypeptides are short linear chains of amino acids. The peptide boundaries generally range from 20-30 amino acids. Polypeptides are used to refer a wide range of proteins. It is essential that functional activity of proteins can be achieved by using molecularchaperones. These chaperones help fold proteins. They do this by interacting with the chain and allowing it to adopt its native three-dimensional conformation.
Proteins are complex macromolecules consisting of chains of amino compounds linked together via amide linkages. Their folding patterns are determined based on the primary structure and amino acid sequence. The majority of polypeptides can be found in cell membranes, plasma membranes, and are surrounded with water and nonpolar hydrocarbons tails. They can be studied in both these environments to determine their function and activity. Various methods have been developed to determine the structure of polypeptides.
An amino acid pool can be used to synthesize peptides. Each amino acid can be made from two different combinations. These combinations produce a structure that looks like a hexagon. In addition, the amino acid sequence is governed by the sequence of the gene that encodes the peptide. Twenty standard amino acids are specified in the genetic code. Peptides are other amino acids such as leucine and pyrrolysine.
PMID: 8939999 by Greene J., et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4.
PMID: 9693046 by Olson T.M., et al. Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively.
*More publications can be found for each product on its corresponding product page