HGNC Approved Gene Symbol: TIMP4Cytogenetic location: 3p25.2 Genomic coordinates (GRCh38): 3:12,153,067-12,158,911 (from NCBI)▼ TEXTThe tissue inhibitors of ...
HGNC Approved Gene Symbol: TIMP4
Cytogenetic location: 3p25.2 Genomic coordinates (GRCh38): 3:12,153,067-12,158,911 (from NCBI)
The tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix.
▼ Cloning and Expression
Greene et al. (1996) identified an EST with homology to known TIMP sequences and cloned the corresponding gene from a human heart cDNA library. The cDNA encodes a 224-amino acid polypeptide 37% similar to TIMP1 (305370) and 51% similar to TIMP2 (188825) and TIMP3 (188826). The gene is expressed as a 1.4-kb transcript abundant in heart and present at low levels in several other tissues. Greene et al. (1996) found that expressed TIMP4 inhibits MMPs in vitro.
Leco et al. (1997) cloned cDNAs encoding mouse Timp4. The predicted Timp4 protein contains the hallmarks of TIMP proteins, including 12 conserved cysteine residues and 2 short conserved sequence motifs. Northern blot analysis of adult mouse tissues detected Timp4 expression in brain, heart, ovary, and skeletal muscle.
▼ Gene Structure
Olson et al., 1998 determined that the TIMP4 gene contains 5 exons that span 6 kb of genomic DNA. They demonstrated a high degree of conservation of gene structure in the TIMP family.
▼ Gene Function
Bigg et al. (1997) demonstrated specific, high-affinity binding between TIMP4 and progelatinase A (MMP2; 120360). Binding appeared to occur mainly via the C-terminal hemopexin-like domain (C domain) of gelatinase A.
Wang et al. (1997) investigated the effect of TIMP4 on the tumorigenic, invasive, and metastatic behaviors of human breast cancer cells. Overexpression of recombinant TIMP4 in breast cancer cells inhibited the invasion potential of the cells in an in vitro invasion assay. When injected into the mammary fat pads of athymic nude mice, breast cancer cells overexpressing TIMP4 had a lower rate of orthotopic tumor growth and showed decreased regional lymph node and lung metastasis compared with control cells.
By FISH, Olson et al., 1998 mapped the TIMP4 gene to chromosome 3p25. By interspecific backcross analysis, they mapped the mouse Timp4 gene to chromosome 6 in a region of syntenic homology with human chromosome 3.