PHB1 (Prohibitin 1): A Multifunctional Scaffold Protein in Mitochondrial Homeostasis, Cell Proliferation, and Disease
Explore the genomic context, expression patterns, disease associations, and functional roles of the PHB1 gene, a conserved regulator of mitochondrial integrity and cellular signaling.
Gene Information Card
| Symbol | PHB1 |
|---|---|
| Full Name | Prohibitin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 5245 ncbi.nlm.nih.gov/gene/5245 |
| Ensembl ID | ENSG00000167085 |
| UniProt ID | P35232 |
| OMIM ID | 176705 |
| HGNC ID | HGNC:8912 |
| Aliases | PHB, BAP32, HEL-215, HEL-S-54 |
Description
PHB1 (Prohibitin 1) is a highly conserved gene encoding a 32 kDa protein that localizes predominantly to the inner mitochondrial membrane, where it acts as a scaffold and chaperone. It is involved in mitochondrial biogenesis, oxidative phosphorylation, and apoptosis regulation. Beyond mitochondria, PHB1 also functions in the nucleus and cytoplasm, modulating transcriptional activity, cell cycle progression, and signal transduction. Its expression is ubiquitous, with elevated levels in metabolically active tissues. PHB1 has been implicated in various cancers, aging, and metabolic disorders, functioning as a tumor suppressor in some contexts and a pro-survival factor in others.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of PHB1 expression or altered localization may promote tumorigenesis; PHB1 interacts with Rb and p53 to regulate cell cycle and apoptosis. | PMID: 11559848; PMID: 15616588 (via NCBI Gene, OMIM) |
| Prostate cancer | PHB1 is downregulated in prostate cancer; its overexpression inhibits cell proliferation and induces apoptosis. | PMID: 10910056; PMID: 11751427 (via NCBI Gene, OMIM) |
| Hepatocellular carcinoma | Reduced PHB1 expression correlates with poor prognosis; PHB1 suppresses EMT and metastasis via Wnt/β-catenin pathway. | PMID: 25944712 (via NCBI Gene) |
| Aging and cellular senescence | PHB1 levels decline with age; knockdown accelerates senescence, while overexpression extends lifespan in model organisms. | PMID: 10521499; PMID: 12110184 (via NCBI Gene, OMIM) |
| Mitochondrial disorders | PHB1 mutations or deficiency impair mitochondrial function, leading to respiratory chain defects and oxidative stress. | ClinVar: PHB1 variants associated with mitochondrial dysfunction (limited clinical significance) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (nTPM ~ 200) | High expression in cardiac muscle, consistent with high mitochondrial content. |
| Liver | High (nTPM ~ 180) | Metabolically active tissue with abundant mitochondria. |
| Skeletal muscle | High (nTPM ~ 170) | High mitochondrial density for energy production. |
| Brain | Moderate (nTPM ~ 80) | Widespread expression, particularly in neurons. |
| Kidney | Moderate (nTPM ~ 90) | Expression in renal tubular cells. |
| Lung | Low (nTPM ~ 30) | Lower expression relative to other tissues. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High (nTPM ~ 150) | Strong expression; used in many PHB1 studies. |
| MCF7 (breast cancer) | Moderate (nTPM ~ 80) | Expression varies with estrogen receptor status. |
| HepG2 (liver cancer) | High (nTPM ~ 170) | High mitochondrial activity. |
| A549 (lung cancer) | Low (nTPM ~ 40) | Lower expression compared to other cancer lines. |
| SH-SY5Y (neuroblastoma) | Moderate (nTPM ~ 70) | Neuronal-like cells with mitochondrial function. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.163C>T (p.Arg55Cys) | Missense | Rare (MAF < 0.01%) | Potential impact on protein stability; clinical significance uncertain. |
| c.404A>G (p.Asn135Ser) | Missense | Rare (MAF < 0.01%) | Located in PHB domain; may affect mitochondrial localization. |
| c.739G>A (p.Val247Ile) | Missense | Rare (MAF < 0.01%) | Near C-terminus; functional effect unknown. |
| c.1-?_*? (whole gene deletion) | Copy number loss | Very rare | Homozygous loss likely lethal; heterozygous loss may contribute to cancer susceptibility. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) are rare in germline; somatic loss of expression via promoter methylation or miRNA regulation is more common in cancer, leading to reduced tumor suppressor activity.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of wild-type PHB1 can have oncogenic effects in some contexts (e.g., promoting cell survival).
Dominant Negative (DN)
Dominant-negative effects are not well documented; however, missense mutations in the PHB domain could interfere with oligomerization, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrial inner membrane | • protein folding |
| • chaperone binding | • cell cycle arrest |
| • apoptotic process | • negative regulation of cell proliferation |
| • response to oxidative stress | • transcription coregulator activity |
| • ubiquitin protein ligase binding | • lipid binding |
Pathways
• Mitochondrial protein import and folding (via PHB complex)
• p53 signaling pathway (PHB1 interacts with p53)
• Retinoblastoma (Rb) pathway (PHB1 regulates Rb/E2F)
• Wnt/β-catenin signaling (inhibition of EMT)
• Apoptosis signaling (mitochondrial pathway)
Protein Summary
Prohibitin 1 (PHB1) is a 272-amino acid protein with a conserved PHB domain and a C-terminal coiled-coil region. It forms high-molecular-weight complexes in the mitochondrial inner membrane, often with PHB2, acting as a scaffold for mitochondrial cristae morphology and protein quality control. PHB1 also translocates to the nucleus upon certain stimuli, where it interacts with transcription factors (e.g., p53, Rb) to regulate gene expression. Post-translational modifications include phosphorylation and ubiquitination, affecting its stability and function. PHB1 is implicated in diverse cellular processes, including proliferation, apoptosis, and stress responses, making it a potential therapeutic target in cancer and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHB1 Knockout HEK293T Cell Line | EDJ-KQ78164 | Human | 5245 | Details Get a Quote |
| PHB1 Knockout A-549 Cell Line | EDJ-KQ78165 | Human | 5245 | Details Get a Quote |
