TIMP-1 HUMAN

General description

TIMP1 (tissue inhibitor of metalloproteinase 1) is a glycoprotein and belongs to the TIMP family of endogenous MMP (matrix metalloproteinase) inhibitors. Humans contain four TIMPs. All TIMPs contain an N-terminal of 125 residues, a 65-residue C-terminal, and both these domains containing three disulfide bonds. The N-terminal domain inhibits MMPs by folding into a separate unit. Recombinant human TIMP-1 is a 20.6 kDa protein containing 184 amino acid residues.

Biochem/physiol Actions

TIMP1 functions as a poor inhibitor of MT1 (membrane type 1)-MMP, MT3-MMP, MT5-MMP and MMP-19. It inhibits ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) protein. In HUVECs, the down-regulation of TIMP1 and up-regulation of MMP-3 results in aberrant endothelium-dependent vasodilation, EC (endothelial cell) death, and endothelial interruption in a FOXO3 (forkhead box O3)-mediated manner. In patients with CAD (coronary artery disease) and acute coronary syndrome (ACS), the urine levels of this protein are elevated. This protein interacts with Bcl-2 (B cell lymphoma) protein, and induces apoptosis in lung adenocarcinoma cells. The plasma levels of this protein are increased in patients with obesity and obesity-related disorders, such as steatosis, where it participates in pathogenesis of diet-induced hepatic steatosis and glucose intolerance.

Sequence

CTCVPPHPQT AFCNSDLVIR AKFVGTPEVN QTTLYQRYEI KMTKMYKGFQ ALGDAADIRF VYTPAMESVC GYFHRSHNRS EEFLIAGKLQ DGLLHITTCS FVAPWNSLSL AQRRGFTKTY TVGCEECTVF PCLSIPCKLQ SGTHCLWTDQ LLQGSEKGFQ SRHLACLPRE PGLCTWQSLR SQIA

Physical form

Lyophilized from 10 mM Sodium Phosphate, pH 7.5.

Reconstitution

Centrifuge the vial prior to opening. Reconstitute in water to a concentration of 0.1-1.0 mg/ml. Do not vortex. This solution can be stored at 2-8°C for up to 1 week. For extended storage, it is recommended to further dilute in a buffer containing a carrier protein (example 0.1% BSA) and store in working aliquots at -20°C to -80°C.