ST13 Human
Description
Co-chaperone Activity
ST13 bridges HSP70 and HSP90, stabilizing their interactions during protein folding. It promotes glucocorticoid receptor maturation by coordinating chaperone cycles .
Tumor Suppression
ST13 expression is downregulated in colorectal carcinoma (CRC), suggesting a role in tumor suppression:
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CRC studies: Overexpression inhibits proliferation and migration, while knockdown enhances tumorigenicity in xenograft models .
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Mechanism: Regulates cell cycle arrest and migration via HSP-mediated pathways .
Pancreatic Disease Modulation
In chronic pancreatitis (CP), ST13 interacts with Sdf2l1 to stabilize the IRE1α-XBP1s pathway, mitigating dysregulated arachidonic acid (AA) metabolism and fibrosis .
Interaction Partners
ST13 binds multiple proteins through its TPR domain:
| Partner | Function | Domain | Source |
|---|---|---|---|
| HSP70 | ATPase-dependent substrate binding | Full-length | |
| HSP90 | Chaperoning glucocorticoid receptors | Full-length | |
| Sdf2l1 | Stabilizes IRE1α-XBP1s signaling | TPR domain (aa 113–214) |
Preclinical Models
| Model | Observation | Outcome | Source |
|---|---|---|---|
| SW620 CRC cells | ST13 overexpression ↓ proliferation, ↑ cycle arrest | Tumor suppression | |
| PRSS1 Transgenic mice | ST13 knockout ↑ fibrosis, lipid dysregulation | CP exacerbation |
Diagnostic Potential
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Micro-PET/CT: 68Ga-FAPI-04 imaging detects pancreatic fibrosis in CP models, enabling early diagnosis .
Therapeutic Targeting
Product Specs
RRQSGAQYGS FPGGFPGGMP GNFPGGMPGM GGGMPGMAGM PGLNEILSDP EVLAAMQDPE VMVAFQDVAQ NPANMSKYQS NPKVMNLISK LSAKFGGQA.
Product Science Overview
HSP70 Interacting Protein (HIP) is a co-chaperone that plays a crucial role in the cellular stress response by interacting with the 70 kDa heat shock proteins (HSP70). HSP70 proteins are molecular chaperones that assist in the folding of nascent proteins, the refolding of misfolded or aggregated proteins, and the transport of proteins across cellular membranes. HIP enhances the function of HSP70 by stabilizing its interaction with client proteins.
HIP belongs to the family of tetratricopeptide repeat (TPR) domain-containing proteins. The TPR domain is a structural motif that mediates protein-protein interactions and is found in various proteins involved in diverse cellular processes.
HIP is characterized by its ability to bind to the C-terminal EEVD motif of HSP70 through its TPR domain. This interaction is essential for the formation of a stable HSP70-HIP complex, which is critical for the proper functioning of the HSP70 chaperone system. HIP is ubiquitously expressed in various tissues and is highly conserved across different species, indicating its fundamental role in cellular homeostasis.
The primary function of HIP is to regulate the activity of HSP70 by stabilizing its interaction with client proteins. This stabilization is crucial for the efficient folding and refolding of proteins, especially under stress conditions such as heat shock. HIP also plays a role in the degradation of misfolded proteins by targeting them to the proteasome for degradation.
HIP interacts with HSP70 through its TPR domain, which binds to the C-terminal EEVD motif of HSP70. This interaction prevents the premature release of client proteins from HSP70, thereby enhancing the chaperone’s ability to fold proteins correctly. Additionally, HIP can recruit other co-chaperones and components of the protein degradation machinery to form multi-protein complexes that facilitate the proper folding and degradation of proteins.
The expression and activity of HIP are regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational modifications. Stress conditions such as heat shock can induce the upregulation of HIP, ensuring an adequate supply of co-chaperones to assist HSP70 in managing the increased load of misfolded proteins. Post-translational modifications, such as phosphorylation, can also modulate the activity of HIP, affecting its interaction with HSP70 and other co-chaperones.
