TIMP2: Tissue Inhibitor of Metalloproteinases 2
Key regulator of extracellular matrix remodeling and cell signaling
Gene Information Card
| Symbol | TIMP2 |
|---|---|
| Full Name | TIMP metallopeptidase inhibitor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 7077 ncbi.nlm.nih.gov/gene/7077 |
| Ensembl ID | ENSG00000035862 |
| UniProt ID | P16035 |
| OMIM ID | 188825 |
| HGNC ID | 11821 |
| Aliases | CSC-21K, DKFZp686I09125, TIMP-2, TIMP2_HUMAN |
Description
TIMP2 (TIMP metallopeptidase inhibitor 2) encodes a member of the tissue inhibitor of metalloproteinases (TIMP) family. The protein inhibits matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAM) family members, playing a critical role in extracellular matrix (ECM) homeostasis, cell proliferation, and angiogenesis. TIMP2 also has MMP-independent functions, including direct effects on cell signaling via integrins and regulation of cell growth.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of TIMP2 alters ECM degradation, promoting invasion and metastasis | COSMIC, ClinVar |
| Fibrosis (liver, lung, kidney) | Imbalance between MMPs and TIMP2 leads to excessive ECM accumulation | NCBI Gene, OMIM |
| Arthritis (rheumatoid, osteoarthritis) | Reduced TIMP2 activity contributes to cartilage degradation | OMIM, PubMed |
| Cardiovascular disease | Altered TIMP2 levels affect vascular remodeling and plaque stability | NCBI Gene |
| Alzheimer's disease | TIMP2 involvement in amyloid-beta clearance and neuroinflammation | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain | 8.3 | Low |
| Colon | 15.2 | Medium |
| Heart | 10.1 | Medium |
| Kidney | 18.7 | High |
| Liver | 14.0 | Medium |
| Lung | 20.4 | High |
| Pancreas | 9.8 | Low |
| Skin | 22.1 | High |
| Spleen | 11.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.5 | Cervical cancer cell line |
| HEK 293 | 14.2 | Embryonic kidney cells |
| A549 | 19.8 | Lung carcinoma |
| MCF7 | 12.1 | Breast cancer |
| HepG2 | 15.6 | Hepatocellular carcinoma |
| K562 | 8.9 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | 0.01% | p.Met1Val; potential loss of start codon |
| c.314C>T | Missense | 0.02% | p.Thr105Ile; reduced MMP inhibition |
| c.434G>A | Missense | 0.005% | p.Gly145Asp; altered protein stability |
| c.589_590insA | Frameshift | <0.001% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish MMP inhibitory activity, e.g., frameshift or nonsense variants leading to truncated protein.
Gain of Function (GOF)
Not well documented; rare variants may enhance MMP binding or alter non-canonical signaling.
Dominant Negative (DN)
Some missense mutations may produce a protein that interferes with wild-type TIMP2 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Matrix metalloproteinase inhibition pathway
• Extracellular matrix remodeling
• TIMP/MMP balance in cancer
• Integrin signaling
Protein Summary
TIMP2 is a 21 kDa secreted protein that forms a complex with pro-MMP2 and MT1-MMP, facilitating MMP2 activation while inhibiting other MMPs. It contains an N-terminal domain that binds the catalytic zinc of MMPs and a C-terminal domain that interacts with pro-MMP2. Beyond MMP inhibition, TIMP2 modulates cell growth, angiogenesis, and apoptosis through interactions with integrins and other receptors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIMP2 Knockout HEK293 Cell Line | EDJ-KQ5937 | Human | 7077 | Details Get a Quote |
| TIMP2 Knockout A-549 Cell Line | EDJ-KQ29485 | Human | 7077 | Details Get a Quote |
| TIMP2 Knockout HCT 116 Cell Line | EDJ-KQ29486 | Human | 7077 | Details Get a Quote |
| TIMP2 Knockout HeLa Cell Line | EDJ-KQ29487 | Human | 7077 | Details Get a Quote |
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