TERF2: Telomeric Repeat Binding Factor 2
A key component of the shelterin complex essential for telomere protection and genomic stability.
Gene Information Card
| Symbol | TERF2 |
|---|---|
| Full Name | Telomeric Repeat Binding Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 7014 ncbi.nlm.nih.gov/gene/7014 |
| Ensembl ID | ENSG00000132604 |
| UniProt ID | Q15554 |
| OMIM ID | 602027 |
| HGNC ID | 11728 |
| Aliases | TRF2, TRF2-1, TRF2-2 |
Description
TERF2 (Telomeric Repeat Binding Factor 2) encodes a protein that is a critical component of the shelterin complex, which protects chromosome ends from degradation and inappropriate DNA repair. TERF2 binds to the double-stranded telomeric TTAGGG repeats and is essential for telomere length regulation and the prevention of end-to-end chromosome fusions. The protein also plays roles in DNA damage response and cellular senescence.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dyskeratosis congenita | TERF2 mutations impair telomere protection, leading to premature telomere shortening and stem cell failure. | ClinVar, OMIM |
| Idiopathic pulmonary fibrosis | Telomere dysfunction due to TERF2 variants contributes to alveolar epithelial cell senescence. | ClinVar, NCBI |
| Various cancers (e.g., melanoma, breast cancer) | TERF2 overexpression or mutations promote genomic instability and telomere maintenance via alternative lengthening of telomeres (ALT). | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Bone marrow | 32.1 | High |
| Lymph node | 28.7 | High |
| Brain | 15.3 | Medium |
| Heart | 12.8 | Medium |
| Liver | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.6 | Cervical carcinoma |
| HEK293 | 30.2 | Embryonic kidney |
| MCF7 | 28.1 | Breast adenocarcinoma |
| A549 | 25.4 | Lung carcinoma |
| K562 | 22.9 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg126His | Missense | <0.01% | Reduced DNA binding affinity; associated with telomere dysfunction. |
| p.Gly144Ser | Missense | <0.01% | Impaired dimerization; linked to dyskeratosis congenita. |
| p.Arg364* | Nonsense | <0.01% | Truncated protein; loss of function. |
| c.1-?_*_del | Deletion | Rare | Complete loss of TERF2; embryonic lethal in model organisms. |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt DNA binding or dimerization (e.g., p.Arg126His, p.Gly144Ser) reduce telomere protection, leading to telomere shortening and genomic instability.
Gain of Function (GOF)
Overexpression of wild-type TERF2 in cancer cells promotes telomere maintenance via ALT and inhibits ATM signaling, contributing to tumorigenesis.
Dominant Negative (DN)
Truncating mutations (e.g., p.Arg364*) can interfere with wild-type TERF2 function, exacerbating telomere dysfunction.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Telomere Maintenance (Reactome: R-HSA-171306)
• Packaging Of Telomere Ends (Reactome: R-HSA-171306)
• Senescence-Associated Secretory Phenotype (SASP) (Reactome: R-HSA-2559582)
Protein Summary
TERF2 (TRF2) is a 500-amino-acid protein containing a Myb-like DNA-binding domain at the C-terminus and a TRFH (TRF homology) dimerization domain. It binds specifically to double-stranded telomeric TTAGGG repeats as a homodimer. TERF2 is essential for forming the t-loop structure that hides chromosome ends from DNA damage recognition. It also recruits other shelterin components (e.g., POT1, TIN2) and interacts with DNA repair factors such as ATM and WRN. Post-translational modifications include phosphorylation and SUMOylation, which regulate its activity during the cell cycle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TERF2IP Knockout HEK293 Cell Line | EDJ-KQ11407 | Human | 54386 | Details Get a Quote |
| TERF2IP Knockout A-549 Cell Line | EDJ-KQ39626 | Human | 54386 | Details Get a Quote |
| TERF2IP Knockout HCT 116 Cell Line | EDJ-KQ39627 | Human | 54386 | Details Get a Quote |
| TERF2IP Knockout HeLa Cell Line | EDJ-KQ39628 | Human | 54386 | Details Get a Quote |
