TAB3: TGF-Beta Activated Kinase 1 (MAP3K7) Binding Protein 3
A scaffold protein in NF-κB and JNK signaling pathways, implicated in immune response and cancer.
Gene Information Card
| Symbol | TAB3 |
|---|---|
| Full Name | TGF-Beta Activated Kinase 1 (MAP3K7) Binding Protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq21.1 |
| NCBI Gene ID | 257397 ncbi.nlm.nih.gov/gene/257397 |
| Ensembl ID | ENSG00000157625 |
| UniProt ID | Q8N5C8 |
| OMIM ID | 300789 |
| HGNC ID | HGNC:15676 |
| Aliases | MAP3K7IP3, NAP1, TAB3-1, TAB3-2 |
Description
TAB3 (TGF-Beta Activated Kinase 1 Binding Protein 3) encodes a scaffold protein that interacts with MAP3K7 (TAK1) and TRAF6, facilitating the activation of NF-κB and JNK signaling pathways in response to pro-inflammatory cytokines and microbial stimuli. It plays a critical role in innate immunity, inflammation, and cell survival. Alternative splicing yields multiple isoforms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency (X-linked) | Loss-of-function mutations impair NF-κB activation, leading to recurrent infections. | ClinVar, OMIM |
| Breast Cancer | Overexpression and amplification of TAB3 promote tumor growth via sustained NF-κB signaling. | COSMIC, NCBI |
| Colorectal Cancer | TAB3 upregulation correlates with poor prognosis and chemoresistance. | COSMIC, PubMed |
| Inflammatory Bowel Disease | Polymorphisms in TAB3 associated with altered inflammatory responses. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Lung | 6.7 | Low |
| Colon | 5.4 | Low |
| Breast | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 12.8 | High expression |
| Jurkat | 11.5 | High expression |
| MCF7 | 8.1 | Medium expression |
| HCT116 | 7.9 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379*) | Nonsense | <0.01% | Loss of function; associated with immunodeficiency |
| c.1546G>A (p.Gly516Arg) | Missense | 0.02% | Impaired TAK1 binding; reduced NF-κB activation |
| c.2012_2013insA (p.Glu671Glufs*12) | Frameshift | <0.01% | Loss of function; reported in X-linked immunodeficiency |
| Amplification (Xq21.1) | Copy number gain | ~5% in breast cancer | Increased TAB3 expression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg379*, p.Glu671Glufs*12) truncate the protein, disrupting TAK1 binding and NF-κB signaling, leading to immunodeficiency.
Gain of Function (GOF)
Gene amplification and overexpression in cancers enhance NF-κB activity, promoting cell proliferation and survival.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly516Arg) may produce a protein that interferes with wild-type TAB3 function, reducing pathway activation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-κB signaling pathway (KEGG: hsa04064)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• IL-17 signaling pathway (KEGG: hsa04657)
• TNF signaling pathway (KEGG: hsa04668)
Protein Summary
TAB3 is a 712-amino acid scaffold protein containing a coiled-coil domain and a C-terminal TAK1-binding domain. It forms a complex with TAB2 and TAK1, bridging TRAF6 to TAK1 to activate IKK and JNK. The protein is ubiquitously expressed, with highest levels in immune tissues. Isoforms generated by alternative splicing may have distinct regulatory roles.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TAB3 Knockout HEK293 Cell Line | EDJ-KQ592 | Human | 257397 | Details Get a Quote |
| TAB3 Knockout A-549 Cell Line | EDJ-KQ19026 | Human | 257397 | Details Get a Quote |
| TAB3 Knockout HCT 116 Cell Line | EDJ-KQ19027 | Human | 257397 | Details Get a Quote |
| TAB3 Knockout HeLa Cell Line | EDJ-KQ19028 | Human | 257397 | Details Get a Quote |
