SIT1 (Signaling Threshold Regulating Transmembrane Adapter 1)
Transmembrane adapter protein involved in immune cell signaling and T-cell activation
Gene Information Card
| Symbol | SIT1 |
|---|---|
| Full Name | Signaling Threshold Regulating Transmembrane Adapter 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 27240 ncbi.nlm.nih.gov/gene/27240 |
| Ensembl ID | ENSG00000137078 |
| UniProt ID | Q9Y3P8 |
| OMIM ID | 608934 |
| HGNC ID | 20234 |
| Aliases | SIT, gp30, MGC117188 |
Description
SIT1 (Signaling Threshold Regulating Transmembrane Adapter 1) is a transmembrane adapter protein primarily expressed in hematopoietic cells. It modulates T-cell receptor (TCR) signaling by recruiting downstream effectors and setting activation thresholds. SIT1 is involved in immune synapse formation and may play roles in autoimmunity and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) | Dysregulation of T-cell apoptosis due to altered SIT1 signaling | PMID: 14557411 |
| T-cell acute lymphoblastic leukemia (T-ALL) | Aberrant SIT1 expression affecting TCR signaling and cell survival | PMID: 21931115 |
| Systemic lupus erythematosus (SLE) | Polymorphisms in SIT1 associated with altered immune activation | PMID: 23143596 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lymph node | 10.8 | Medium |
| Thymus | 9.2 | Medium |
| Bone marrow | 6.7 | Low |
| Peripheral blood leukocytes | 8.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.3 | High expression |
| Raji (Burkitt lymphoma) | 4.2 | Low expression |
| K562 (chronic myeloid leukemia) | 2.1 | Very low expression |
| HEK293 (embryonic kidney) | 0.5 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.247G>A (p.Gly83Arg) | Missense | <0.01% | Altered protein stability and signaling |
| c.334C>T (p.Arg112Trp) | Missense | <0.01% | Impaired adapter function |
| c.421_423del (p.Phe141del) | In-frame deletion | <0.01% | Loss of transmembrane domain |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly83Arg) reduce protein stability and disrupt TCR signaling.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T-cell receptor signaling pathway (KEGG hsa04660)
• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome R-HSA-198933)
Protein Summary
SIT1 is a 30 kDa transmembrane adapter protein with a short extracellular domain and a cytoplasmic tail containing multiple tyrosine-based signaling motifs. It is expressed on T cells, NK cells, and dendritic cells. Upon TCR engagement, SIT1 becomes phosphorylated and recruits SH2 domain-containing proteins such as SHP-2, modulating downstream signaling thresholds.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIT1 Knockout HEK293 Cell Line | EDJ-KQ8726 | Human | 27240 | Details Get a Quote |
| SIT1 Knockout HeLa Cell Line | EDJ-KQ56039 | Human | 27240 | Details Get a Quote |
| SIT1 Knockout A-549 Cell Line | EDJ-KQ64525 | Human | 27240 | Details Get a Quote |
| SIT1 Knockout HCT 116 Cell Line | EDJ-KQ72983 | Human | 27240 | Details Get a Quote |
