STIP1: Stress-Induced Phosphoprotein 1 (HOP)
A key co-chaperone regulating HSP70/HSP90 function and implicated in cancer, neurodegeneration, and protein misfolding disorders.
Gene Information Card
| Symbol | STIP1 |
|---|---|
| Full Name | Stress-induced phosphoprotein 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 10963 ncbi.nlm.nih.gov/gene/10963 |
| Ensembl ID | ENSG00000168439 |
| UniProt ID | P31948 |
| OMIM ID | 605063 |
| HGNC ID | 11387 |
| Aliases | HOP, IEF-SSP-3521, P60, STI1 |
Description
STIP1 (stress-induced phosphoprotein 1), also known as HOP (HSP70/HSP90-organizing protein), encodes a co-chaperone that mediates the association of heat shock proteins HSP70 and HSP90. It plays a critical role in protein folding, maturation, and stabilization of client proteins, including steroid hormone receptors and kinases. STIP1 is involved in cellular stress responses and has been linked to cancer progression, neurodegenerative diseases, and viral replication.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, prostate, lung, colorectal) | Overexpression of STIP1 enhances HSP90 chaperone activity, promoting stabilization of oncogenic client proteins (e.g., HER2, AKT, HIF-1α) and tumor growth. | PMID: 25605274, 27816943 |
| Alzheimer's disease | STIP1 co-localizes with tau aggregates and modulates tau pathology by facilitating HSP90-mediated tau misfolding and aggregation. | PMID: 23951060, 30397376 |
| Prion disease | STIP1 interacts with prion protein (PrP) and modulates prion replication and neurotoxicity. | PMID: 19124763 |
| Huntington's disease | STIP1 levels are altered in Huntington's disease models, affecting mutant huntingtin aggregation and toxicity. | PMID: 21504834 |
| Viral infection (e.g., influenza, HIV) | STIP1 is hijacked by viruses to facilitate viral protein folding and replication. | PMID: 22438542 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.2 | Low |
| Liver | 15.3 | Medium |
| Kidney | 10.1 | Medium |
| Testis | 18.7 | High |
| Lung | 9.8 | Low |
| Colon | 11.4 | Medium |
| Breast | 7.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| MCF7 | 16.8 | Breast cancer cell line |
| A549 | 11.5 | Lung cancer cell line |
| HEK293 | 13.0 | Embryonic kidney cell line |
| SH-SY5Y | 15.1 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.113C>T (p.Pro38Leu) | Missense | <0.1% | Reported in ClinVar as variant of uncertain significance; potential effect on protein stability. |
| c.487G>A (p.Gly163Arg) | Missense | <0.1% | Observed in COSMIC in colorectal cancer; functional impact unknown. |
| c.1024A>G (p.Ile342Val) | Missense | <0.1% | Rare population variant; no known disease association. |
| c.1345C>T (p.Arg449Cys) | Missense | <0.1% | Reported in ClinVar; uncertain significance. |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in human disease; STIP1 knockout is embryonic lethal in mice.
Gain of Function (GOF)
Overexpression (not mutation) is the primary gain-of-function mechanism in cancer, enhancing HSP90 chaperone activity.
Dominant Negative (DN)
No dominant-negative mutations described in the literature.
View complete mutation data：
Gene Ontology (GO)
| • chaperone binding (GO:0051087) | • ubiquitin protein ligase binding (GO:0031625) |
| • unfolded protein binding (GO:0051082) | • protein folding (GO:0006457) |
| • cellular response to heat (GO:0034605) | • cytosol (GO:0005829) |
| • nucleus (GO:0005634) |
Pathways
• HSP90 chaperone cycle for steroid hormone receptors (S100A8/A9
• HSP70/HSP90)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Chaperone-mediated autophagy
• p53 signaling pathway (indirect via client proteins)
Protein Summary
STIP1 (HOP) is a 543-amino-acid co-chaperone with three tetratricopeptide repeat (TPR) domains that mediate simultaneous binding to HSP70 and HSP90. It facilitates the transfer of client proteins from HSP70 to HSP90, a critical step in the maturation of steroid hormone receptors, kinases, and transcription factors. STIP1 is highly expressed in testis, brain, and various cancers. Its overexpression correlates with poor prognosis in multiple malignancies. The protein is also implicated in neurodegenerative tauopathies and prion disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STIP1 Knockout HEK293 Cell Line | EDJ-KQ3790 | Human | 10963 | Details Get a Quote |
| STIP1 Knockout HeLa Cell Line | EDJ-KQ24537 | Human | 10963 | Details Get a Quote |
| STIP1 Knockout A-549 Cell Line | EDJ-KQ25893 | Human | 10963 | Details Get a Quote |
| STIP1 Knockout HCT 116 Cell Line | EDJ-KQ25894 | Human | 10963 | Details Get a Quote |
