TIFA (TRAF Interacting Protein With Forkhead Associated Domain)
Key regulator of NF-κB signaling and innate immunity
Gene Information Card
| Symbol | TIFA |
|---|---|
| Full Name | TRAF Interacting Protein With Forkhead Associated Domain |
| Gene Type | protein-coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 92610 ncbi.nlm.nih.gov/gene/92610 |
| Ensembl ID | ENSG00000138684 |
| UniProt ID | Q96CG3 |
| OMIM ID | 607222 |
| HGNC ID | 19050 |
| Aliases | T2BP, FLJ22965, MGC10744 |
Description
TIFA (TRAF Interacting Protein With Forkhead Associated Domain) is a protein-coding gene that encodes a key adaptor molecule in the NF-κB signaling pathway. It contains a forkhead-associated (FHA) domain that mediates interactions with TRAF proteins, particularly TRAF2 and TRAF6, to regulate immune and inflammatory responses. TIFA is involved in the activation of NF-κB in response to various stimuli, including bacterial components and cytokines.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease | Dysregulated NF-κB activation via TIFA-TRAF6 interaction | PMID: 25736436 |
| Rheumatoid arthritis | Enhanced TIFA expression promotes synovial inflammation | PMID: 28424237 |
| Gastric cancer | TIFA overexpression linked to Helicobacter pylori-induced NF-κB activation | PMID: 19668353 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Low |
| Lung | 6.1 | Low |
| Colon | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression in kidney-derived line |
| HeLa | 9.8 | Moderate expression in cervical cancer line |
| THP-1 | 7.5 | Monocytic line, induced by LPS |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236C>T (p.Pro79Leu) | Missense | <0.01% | Unknown functional effect |
| c.487G>A (p.Gly163Arg) | Missense | <0.01% | Predicted damaging by SIFT |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation initiation |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants may impair FHA domain binding to TRAF6, reducing NF-κB activation.
Gain of Function (GOF)
Not well documented; overexpression in cancer may constitutively activate NF-κB.
Dominant Negative (DN)
Mutations disrupting TRAF interaction could act as dominant-negative inhibitors of signaling.
View complete mutation data：
Gene Ontology (GO)
| • NF-κB-inducing kinase activity | • protein kinase binding |
| • TRAF binding | • signal transduction |
| • innate immune response | • positive regulation of NF-κB transcription factor activity |
Pathways
• NF-kappa B signaling pathway (KEGG: hsa04064)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
Protein Summary
TIFA is a 184-amino acid protein (21 kDa) containing a single N-terminal FHA domain. It functions as an adaptor that links upstream signals to TRAF proteins, promoting TRAF6 oligomerization and subsequent activation of the IKK complex and NF-κB. TIFA is phosphorylated by TAK1, enhancing its interaction with TRAF6. It is widely expressed in immune tissues and plays a role in antibacterial defense and inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIFA Knockout HEK293 Cell Line | EDJ-KQ1423 | Human | 92610 | Details Get a Quote |
| TIFAB Knockout HEK293 Cell Line | EDJ-KQ15732 | Human | 497189 | Details Get a Quote |
| TIFA Knockout A-549 Cell Line | EDJ-KQ22266 | Human | 92610 | Details Get a Quote |
| TIFA Knockout HCT 116 Cell Line | EDJ-KQ22268 | Human | 92610 | Details Get a Quote |
| TIFA Knockout HeLa Cell Line | EDJ-KQ22269 | Human | 92610 | Details Get a Quote |
| TIFAB Knockout HeLa Cell Line | EDJ-KQ60486 | Human | 497189 | Details Get a Quote |
| TIFAB Knockout A-549 Cell Line | EDJ-KQ68956 | Human | 497189 | Details Get a Quote |
| TIFAB Knockout HCT 116 Cell Line | EDJ-KQ77315 | Human | 497189 | Details Get a Quote |
| Tifa Knockout IBMDM Cell Line | EDC90295 | Mouse | 211550 | Details Get a Quote |
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