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STIMATE

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

Background

The STIMATE gene is located in the 3p21.1 region of the human chromosome and encodes the STIM-activating enhancer (STIMATE), also known as transmembrane protein 110 (TMEM110), a member of the STIMATE protein family. STIMATE is a multi-pass transmembrane protein anchored in the endoplasmic reticulum membrane, with five predicted transmembrane domains and both N- and C-termini oriented toward the cytosol. Its molecular weight is approximately 33 kDa and it is broadly expressed in human tissues, with relatively higher levels detected in placenta and liver. As an important regulator of store-operated calcium entry (SOCE), STIMATE physically interacts with the ER calcium sensor STIM1 to facilitate its conformational switch and subsequent clustering at ER-plasma membrane (ER-PM) junctions, thereby promoting coupling with the ORAI1 calcium channel and activation of downstream calcium-dependent signaling pathways. These processes are involved in the regulation of calcium homeostasis, signal transduction, and the dynamic organization of membrane contact sites. The protein harbors a KxRxRR ER-retention motif essential for its subcellular localization, as well as a GXXXG motif that may contribute to oligomerization. The C-terminal region of STIMATE mediates direct binding to the CC1 domain of STIM1. Additionally, STIMATE contributes to both the long-term maintenance and short-term remodeling of ER-PM junction architecture. Therefore, STIMATE is regarded as a valuable molecular target for studying calcium signaling and inter-organelle communication. Its functional characterization provides important tools for understanding the spatial and temporal regulation of store-operated calcium entry and the molecular architecture of membrane contact sites.

Fig.1 Gene duplications and losses in the STIMATE family. (OA Literature)Fig. 1 Main gene duplications and losses derived from the STIMATE gene family tree.1

Function of STIMATE Protein: An Important Mediator of Store-Operated Calcium Signaling at ER-PM Junctions

The functional spectrum of STIMATE centers on the regulation of store-operated calcium signaling and inter-organelle communication:

  • Regulation of STIM1 activation and SOCE: STIMATE physically interacts with the CC1 domain of STIM1, promoting a conformational switch that facilitates STIM1 oligomerization and puncta formation at ER-PM junctions. This interaction is important for the efficient coupling of STIM1 with the plasma membrane calcium channel ORAI1, thereby initiating store-operated calcium entry.
  • ER-PM junction organization and remodeling: STIMATE contributes to both the long-term maintenance of ER-PM junction architecture and the rapid, short-term remodeling of these contact sites during calcium store depletion. It has been reported to cooperate with STIM2 in the early steps of junctional rearrangement, ensuring the spatial organization required for effective STIM-ORAI signaling.
  • Regulation of calcium-dependent signaling cascades: Through its role in promoting STIM1-ORAI1 coupling and sustained calcium influx, STIMATE influences downstream calcium-dependent signaling pathways, including NFAT activation. The modulation of SOCE by STIMATE has implications for calcium-dependent transcriptional programs and cellular responses to environmental cues.
  • Structure-function relationships and molecular interactions: The C-terminal region of STIMATE mediates its direct interaction with STIM1, while the KxRxRR motif ensures proper ER retention. A GXXXG motif within the transmembrane region may facilitate protein oligomerization. Elucidating the structural basis of STIMATE-STIM1 recognition and the molecular determinants of ER-PM junction targeting provides insights into the regulatory mechanisms of membrane contact site organization.

STIMATE Membrane Protein Product

Creative Biolabs offers a comprehensive series of high-quality STIMATE membrane protein products designed to support structural and functional investigations of store-operated calcium entry. Built upon the independently developed MemDX™ recombinant membrane protein technology platform, STIMATE proteins can be prepared through multiple expression systems, including virus-like particles (VLP) and in vitro prokaryotic expression systems, among others. These rigorously characterized protein products, which include MemDX™ recombinant human STIMATE membrane protein (as virus-like particles) and human STIMATE proteins derived from diverse expression systems, are suitable for ELISA, antibody screening and identification, binding experiments, and functional research, equipping investigators with dependable reagents for analyzing STIMATE-mediated regulation of STIM1 activation and calcium signaling mechanisms.

STIMATE Protein Product

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STIMATE Stable Cell Line Product

Constructing a robust cell model is crucial for investigating STIMATE function in store-operated calcium signaling. As an ER-resident protein that promotes STIM1 conformational switching and puncta formation at ER-PM junctions, the expression level and subcellular distribution of STIMATE directly affect the efficiency of SOCE and downstream calcium-dependent signaling. Alterations in STIMATE expression or its targeting to ER-PM junctions may lead to significant changes in calcium homeostasis. Creative Biolabs offers customized STIMATE membrane protein stable transfection cell models, covering wild-type and various engineered forms. These models stably express the target protein on the endoplasmic reticulum membrane, and are suitable for studies on STIM1 interaction dynamics, calcium imaging, ER-PM junction visualization, and quantitative assessment of SOCE activity, providing a reliable and reproducible platform for exploring the molecular mechanism, structure-function relationship, and regulatory role of STIMATE in inter-organelle communication. Our technology ensures correct protein localization and ER membrane integrity, facilitating your research.

STIMATE Stable Cell Line Product

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

STIMATE Recombinant Antibody Product

Creative Biolabs offers highly specific recombinant antibodies targeting STIMATE, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our STIMATE recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in STIMATE expression levels in various tissues or cell sources, analyze its subcellular localization at ER-PM junctions, and conduct related research such as protein interaction with STIM1 and calcium signaling pathway analysis. These antibodies provide reliable detection tools for the structural analysis, functional study of STIMATE, and the investigation of its role in ER-PM communication and calcium homeostasis.

STIMATE Recombinant Antibody Product

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

Product Features

  • Multiple expression platforms: Recombinant proteins can be produced through several expression systems (encompassing virus-like particles and both prokaryotic and eukaryotic hosts), addressing the requirements of diverse experimental settings.
  • Broad experimental compatibility: The products are suitable for use in ELISA, antibody screening, binding assays, Western Blot, immunofluorescence, immunohistochemistry, and related applications.
  • Consistent quality across batches: Strict quality control measures maintain product uniformity between batches, ensuring experimental results remain reproducible and dependable.
  • Tailored customization services: Personalized services are available for specific protein forms, labeling approaches, or preferred expression platforms.

Custom STIMATE Membrane Protein and Antibody Discovery Services

In addition to the standard products, Creative Biolabs also offers professional customized services for STIMATE. STIMATE is a multi-pass ER-resident membrane protein containing distinct functional domains involved in STIM1 interaction and ER-PM junction targeting. These structural features present specific requirements in aspects such as membrane protein expression, antigen design, and functional characterization. Leveraging our technology platform, we can assist you in completing the following customized projects:

  • Customized production of ER-resident multi-transmembrane proteins: Tailored expression (using multiple expression systems), purification, and characterization for full-length STIMATE and its functional domains.
  • Customized antibody development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant antibodies), supporting detection of distinct STIMATE conformations or common epitope recognition.
  • Construction of stable cell models: Generate stable cell models expressing wild-type or engineered STIMATE, suitable for calcium imaging and ER-PM junction studies.
  • Development of functional detection systems: Design and execute experimental protocols such as calcium flux assays, STIM1 interaction analysis, and quantitative assessment of SOCE activity.

Frequently Asked Questions (FAQ)

  1. What is the main function of the STIMATE protein?

    STIMATE functions as a positive regulator of store-operated calcium entry (SOCE) at ER-plasma membrane junctions. It physically interacts with the ER calcium sensor STIM1, facilitating its conformational switch and clustering at ER-PM contact sites to enable coupling with ORAI1 calcium channels. Through this mechanism, STIMATE modulates calcium influx and downstream calcium-dependent signaling pathways, including NFAT activation. Additionally, STIMATE contributes to the maintenance and remodeling of ER-PM junction architecture, serving as an important model for studying inter-organelle communication and calcium homeostasis.

  2. Why is STIMATE an important research target?

    STIMATE plays a central role in organizing ER-PM membrane contact sites, which are critical signaling hubs for calcium-dependent cellular processes. Investigating STIMATE provides insights into the molecular mechanisms governing STIM1 activation, the spatial organization of calcium signaling complexes, and the dynamic regulation of membrane contact site architecture. Understanding STIMATE function is valuable for elucidating fundamental principles of inter-organelle communication and calcium signal transduction.

  3. Is the STIMATE product of Creative Biolabs suitable for clinical applications?

    Not applicable. All STIMATE products and services provided by Creative Biolabs are for research purposes only and cannot be used for any clinical diagnosis, prevention, treatment or cure of any disease.

  4. What types of STIMATE products does Creative Biolabs offer?

    We offer a variety of product types, including recombinant STIMATE membrane proteins, stable cell models expressing STIMATE, high-quality recombinant STIMATE antibodies, as well as comprehensive customized services.

Reference
  1. Song, Jia, et al. "Integrated pipeline for inferring the evolutionary history of a gene family embedded in the species tree: a case study on the STIMATE gene family." BMC bioinformatics 18.1 (2017): 439. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1186/s12859-017-1850-2
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