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SIT1

Products

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

SIT1 is a small ~20–22 kDa type‐III single pass membrane well-characterized surface molecule found primarily expressed in hematopoietic lineages. SIT1 is composed of a short extracellular N-terminal region, one membrane-spanning alpha-helical domain and an extended cytoplasmic tail containing multiple immunoreceptor tyrosine-based inhibition motifs (ITIMs) as well as Src homology 2 (SH2) domain-binding sites. SIT1 is rapidly tyrosine phosphorylated upon engagement of the T-cell receptor (TCR) or B-cell receptor (BCR), generating docking sites for SHP-1 and -2 as well as Grb2, a mediator critical in regulating intracellular signalling events. This molecular assembly raises the qualitative threshold necessary for full lymphocyte activation by reducing proximal phosphorylation events, including ZAP-70, LAT, SLP-76 and PLCγ1; calcium mobilization downstream from TCR engagement as well as MAPK signaling and NF-κB nuclear translocation. In this capacity, SIT1 serves as an essential rheostat that inhibits spontaneous autoimmunity while maintaining the potential for strong pathogen-specific immune responses. Besides classical T and B lymphocytes, SIT1 regulates NK cell education, iNKTcell development and functional plasticity of tissue-resident memory lymphocytes. In clinical contexts, dysregulated expression of SIT1 or mutations at its phosphorylation sites have been implicated in systemic lupus erythematosus, rheumatoid arthritis and lymphoproliferative syndromes. Dysregulated SIT1 signaling in the tumor microenvironment may affect T-cell activation versus exhaustion balance, therefore impacting checkpoint inhibitor sensitivity. Together, these convergent immunological features position SIT1 as an essential target for biologics to restore tolerance and next-generation checkpoint modulation, but also precision autoimmune therapeutics.

Fig.1 Identification of SIT1 homozygous variant. (OA Literature)Fig.1 Identification of a patient with a SIT1 homozygous variant.1

SIT1 Is A Versatile Immune Threshold Orchestrator

SIT1 orchestrates multiple immune programs that go beyond its classical act as a simple signal attenuator:

  • TCR/BCR Signal Dampener: SIT1 dephosphorylates proximal adaptors by recruiting SHP-1 and SHP2 to the plasma membrane on receptor engagement, thereby increasing Ag stimulus threshold necessary for optimal lymphocyte activation. This negative feedback loop is responsible for the inability of low-affinity self-peptides or weak pathogen-derived antigens to elicit inappropriate effector responses, ensuring peripheral tolerance.
  • Autoimmune Gatekeeper: SIT1 genetic ablation or functional deficiency decreases the activation thresholds of T-cells, resulting in spontaneous autoimmunity occurring prematurely in animal models. Thus, restoring SIT1 expression or increasing its phosphatase-recruitment ability is a logical therapeutic approach for systemic lupus and type 1 diabetes as well as inflammatory bowel disease where inappropriate lymphocyte activation leads to tissue destruction.
  • Tumor Immunity Modulator: The expression of SIT1 on tumor-infiltrating T cells has been shown to have an effect on the balance between productive anti-tumor immunity and dysfunctional exhaustion in a tumor microenvironment. Chemano-pharmacological fine-tuning of SIT1 activity, whether through increased anchoring to the membrane under conditions that may lead to hyperactivation or via transitory inhibition release concomitant cytolytic function in a combination immuno-oncologic setting.

SIT1 Membrane Protein Product

We present a diverse panel of highly purified full-length and engineered SIT1 transmembrane protein constructs designed to support structural and functional studies of this immune adaptor. Because membrane topology, cytoplasmic tyrosine phosphorylation, and accessibility of signaling motifs can influence SIT1-mediated protein interactions, our protein production strategies are tailored to preserve key structural and biochemical properties relevant to downstream research. These SIT1 research constructs can support phosphorylation studies, protein–protein interaction assays, structural characterization, and screening applications focused on SIT1-associated signaling mechanisms. Protein format, preparation conditions, phosphorylation state, and applicable functional assays are selected and confirmed according to specific project requirements. Quality control and characterization strategies are likewise tailored to the intended experimental application.

SIT1 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

SIT1 Stable Cell Line Product

Functionally relevant cell-based platforms that mimic the physiological cellular microenvironment are needed to decipher SIT1-mediated immunoregulatory thresholds and promote therapeutic pathways for enhanced adhesion. We provide the research community with well-established SIT1 stable cell lines characterized by authentic TCR/BCR plasma membrane localization along with status-neutral basal & inducible tyrosine phosphorylation capacity when either receptor is stimulated. Alongside wild-type SIT1, our platforms comprise constitutive ITIM mutants, disease-associated tyrosine to phenylalanine variants and reporter systems linking NFAT, NF-κB or IL-2 promoter elements with luciferase for real-time quantifying of signaling. We also offer knockdown rescue systems, and lines co-expressing SHP-1 or SHP-2 to interrogate the kinetics of phosphatase recruitment. All clones are stringently validated through verification of genomic integration, surface staining and functional validation in calcium flux, proliferation and T-cell activation assays. These scalable cellular resources provide critical substrates for studies of autoimmune mechanisms and screening compounds with immunomodulatory potential, as well as preclinical optimization of biologics antagonizing the SIT1 axis.

SIT1 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

SIT1 Recombinant Antibody Product

SIT1 monoclonal antibodies: enhance your SIT1 investigations with a focused selection of sequence-defined, high-affinity monoclonal antibodies developed to recognize SIT1. Depending on the individual clone, antibodies may recognize epitopes within different regions of SIT1 and support species-specific detection as documented in the corresponding datasheet. Validated applications may include Western blotting, ELISA, flow cytometric analysis, immunofluorescence and confocal microscopy, and immunohistochemistry, depending on the characteristics and validation data available for each antibody. These reagents can support studies of SIT1 expression across immune cell subsets, cellular localization, and signaling-associated changes. Epitope specificity, species reactivity, phosphorylation-state recognition, cross-reactivity, and suitability for functional assays should be determined according to the clone-specific datasheet and available experimental evidence.

SIT1 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom SIT1 Membrane Protein and Antibody Discovery Services

Extending our standard catalog, we offer comprehensive, end-to-end design and engineering services purpose-built for SIT1-focused programs:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous SIT1 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Can your SIT1 recombinant proteins be administered to human subjects for therapeutic modulation of T-cell activation thresholds, autoimmune disease, or transplant tolerance?

    No—our SIT1 reagents including recombinant proteins, stable cell lines and antibody assays are produced solely for non-clinical research.

  2. Does it have a stable cell line of doxycycline-inducible SIT1 expression that can model kinetics and timing to be investigated on T-cell anergy onset, peripheral tolerance establishment and autoreactive clone deletion?

    Yes, we have constructed stable lines in which SIT1 transcription is placed under a doxycycline-responsive promoter. This arrangement permits precise initiation of expression at defined time points and subsequent monitoring of progressive SHP-1 recruitment, CD3ζ chain dephosphorylation, and IL-2 transcriptional suppression with temporal resolution, eliminating the chronic T-cell exhaustion and compensatory PD-1 upregulation inherent to constitutive overexpression systems.

  3. Is membrane targeting only necessary for phosphatase recruitment to your SIT1 products?

    Yes. We will prepare SIT1 constructs for these purposes that are inserted as expected into phospholipid bilayers with the cytoplasmic tail in a position to stall recruiting of cellular phosphatases and/or immune receptor engagement.

  4. Do your SIT1 products need special post-translational modifications for functionality?

    Our products maintain both the tyrosine residues and membrane topology necessary for phosphorylated (inducible) SHP-1 / SHP-2 recruitment. Phospho-state profiling is also part of the quality control process to ensure these regulatory sites are intact and accessible.

Reference
  1. Chen, Pu, et al. "Homozygous loss-of-function mutation in SIT1 leads to combined immunodeficiency due to dysregulated T cell receptor signaling." Journal of Allergy and Clinical Immunology (2026). Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1016/j.jaci.2026.03.030
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