TIAM1: T-Cell Lymphoma Invasion and Metastasis 1
A key RAC1 guanine nucleotide exchange factor (GEF) in cell migration, polarity, and cancer progression
Gene Information Card
| Symbol | TIAM1 |
|---|---|
| Full Name | T-cell lymphoma invasion and metastasis 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 7074 ncbi.nlm.nih.gov/gene/7074 |
| Ensembl ID | ENSG00000156299 |
| UniProt ID | Q13009 |
| OMIM ID | 600687 |
| HGNC ID | 11805 |
| Aliases | TIAM-1, T lymphoma invasion and metastasis inducing protein 1 |
Description
TIAM1 (T-cell lymphoma invasion and metastasis 1) encodes a guanine nucleotide exchange factor (GEF) that specifically activates RAC1, a small GTPase of the Rho family. Through RAC1 activation, TIAM1 regulates cytoskeletal remodeling, cell adhesion, migration, and polarity. It is implicated in cancer invasion and metastasis, particularly in T-cell lymphomas, breast cancer, and colorectal cancer. TIAM1 also plays roles in neuronal development and synaptic plasticity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell lymphoma | TIAM1 overexpression promotes RAC1-mediated invasion and metastasis | PMID: 10655551, COSMIC |
| Breast cancer | TIAM1 amplification and overexpression correlate with poor prognosis and metastatic spread | PMID: 19029980, COSMIC |
| Colorectal cancer | TIAM1 mutations and altered expression contribute to tumor progression via RAC1 signaling | PMID: 23104886, COSMIC |
| Prostate cancer | TIAM1 upregulation enhances cell motility and invasion through RAC1 activation | PMID: 20010872, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.5 | Medium |
| Lung | 8.2 | Low |
| Breast | 6.1 | Low |
| Colon | 5.3 | Low |
| Lymph node | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.3 | Embryonic kidney, moderate expression |
| HeLa | 9.8 | Cervical carcinoma, moderate expression |
| MCF7 | 7.4 | Breast cancer, low expression |
| Jurkat | 15.1 | T-cell leukemia, high expression |
| HCT116 | 6.5 | Colorectal carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2572C>T (p.Arg858Trp) | Missense | <0.1% | Alters GEF domain, potential loss of function |
| c.3446G>A (p.Arg1149Gln) | Missense | <0.1% | Located in PH domain, unknown significance |
| c.1234_1235insA (p.Thr412Asnfs*3) | Frameshift | <0.1% | Truncation, loss of function |
| c.4567C>T (p.Arg1523*) | Nonsense | <0.1% | Premature stop, loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr412Asnfs*3, p.Arg1523*) lead to truncated protein lacking functional GEF domain, impairing RAC1 activation.
Gain of Function (GOF)
Missense mutations in the GEF domain (e.g., p.Arg858Trp) may alter substrate specificity or increase RAC1 activation, though functional data are limited.
Dominant Negative (DN)
No well-characterized dominant-negative TIAM1 mutations reported in ClinVar or COSMIC.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAC1 signaling pathway (Reactome: R-HSA-9013405)
• Rho GTPase cycle (Reactome: R-HSA-194840)
• Signaling by Rho family GTPases (Reactome: R-HSA-194315)
• Axon guidance (Reactome: R-HSA-422475)
Protein Summary
TIAM1 is a 1591-amino acid multidomain protein containing an N-terminal PH domain, a PDZ domain, a central DH (Dbl homology) domain responsible for GEF activity, and a C-terminal PH domain. It specifically catalyzes the exchange of GDP for GTP on RAC1, promoting active RAC1 signaling. TIAM1 localizes to the plasma membrane and regulates cell polarity, adhesion, and migration. Its expression is tightly controlled in normal tissues but frequently dysregulated in cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIAM1 Knockout HEK293 Cell Line | EDJ-KQ1237 | Human | 7074 | Details Get a Quote |
| TIAM1 Knockout HCT 116 Cell Line | EDJ-KQ20586 | Human | 7074 | Details Get a Quote |
| TIAM1 Knockout HeLa Cell Line | EDJ-KQ20587 | Human | 7074 | Details Get a Quote |
| TIAM1 Knockout A-549 Cell Line | EDJ-KQ63140 | Human | 7074 | Details Get a Quote |
