Prohibitin (PHB)
The protein contains 272 amino acids for an estimated molecular weight of 29804 Da.
Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:28017329, PubMed:31522117). Plays a role in adipose tissue and glucose Homeostasis in a sex-specific manner (By similarity). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity).', 'In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates DDX58/RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6 ( (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| a breast cancer sample | |
| a breast cancer sample |
Biological Process
Activation of phospholipase C activity
Activation of protein kinase C activity
Animal organ regeneration
Antiviral innate immune response
B cell activation
CD40 signaling pathway
Cellular response to interleukin-6
DNA biosynthetic process
Histone deacetylation
Immunoglobulin production
Interleukin-17 production
Mitochondrial calcium ion transmembrane transport
Mitochondrion organization
Modulation by host of viral RNA genome replication
Negative regulation of androgen receptor signaling pathway
Negative regulation of apoptotic process
Negative regulation of cell growth
Negative regulation of cell population proliferation
Negative regulation of ERK1 and ERK2 cascade
Negative regulation of glucocorticoid receptor signaling pathway
Negative regulation of protein catabolic process
Negative regulation of transcription by competitive promoter binding
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription, DNA-templated
Osteoblast differentiation
Ovarian follicle atresia
Ovarian follicle development
Positive regulation of cell death
Positive regulation of complement activation
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of G protein-coupled receptor signaling pathway
Positive regulation of gene expression
Positive regulation of immunoglobulin production
Positive regulation of interleukin-17 production
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of protein kinase B signaling
Positive regulation of smooth muscle cell proliferation
Positive regulation of transcription, DNA-templated
Progesterone receptor signaling pathway
Protein stabilization
Regulation of apoptotic process
Regulation of transcription, DNA-templated
Response to drug
Response to ethanol
Response to immobilization stress
Response to peptide hormone
RIG-I signaling pathway
Signal transduction
T-helper 17 type immune response
Viral entry into host cell
Cellular Component
Cell surface
Cytoplasm
Early endosome
Extracellular exosome
Extrinsic component of mitochondrial outer membrane
Extrinsic component of presynaptic active zone membrane
GABA-ergic synapse
Glutamatergic synapse
Integral component of plasma membrane
Membrane
Mitochondrial crista
Mitochondrial inner membrane
Mitochondrial prohibitin complex
Mitochondrion
Myelin sheath
Nucleoplasm
Nucleus
Plasma membrane
Postsynaptic density
Molecular Function
Complement component C3a binding
Complement component C3b binding
DNA-binding transcription factor activity, RNA polymerase II-specific
Enzyme binding
Histone deacetylase binding
Protein C-terminus binding
Protein heterodimerization activity
Proteinase activated receptor binding
Transcription cis-regulatory region binding
Transcription corepressor activity
Transcription regulatory region DNA binding
The reference OMIM entry for this protein is 176705
Prohibitin; phb
Phb1
DESCRIPTION
Prohibitin is a 30-kD intracellular, antiproliferative protein (White et al., 1991).MAPPING
White et al. (1991) mapped the PHB gene to chromosome 17 by analysis of human-mouse somatic cell hybrid cell lines using a genomic fragment of human prohibitin DNA isolated from a library using the rat prohibitin cDNA clone. By a study of cell lines containing portions of human chromosome 17, they determined that the PHB gene was located in the 17q11.2-q23 region. By in situ hybridization, they localized the gene to 17q21. Sato et al. (1992) isolated the human homolog of the rat prohibitin gene and mapped it to 17q12-q21 by in situ hybridization.GENE FAMILY
Sato et al. (1993) showed that the human prohibitin gene family consists of 1 functional PHB gene on 17q21 and 4 processed pseudogenes, each on a different chromosome: PHBP1 on 6q25, PHBP2 on 11p11.2, PHBP3 on 1p31.3, and PHBP4 on 2q21.GENE FUNCTION
Proliferation of tumor cells depends on new blood vessel formation (angiogenesis) that accompanies malignant progression. Anticancer therapies using angiogenesis inhibitors or cytotoxic agents targeted to the vasculature of tumors have been evaluated in clinical trials. Although white fat is a nonmalignant tissue, it has the capability to quickly proliferate and expand. Furthermore, it is highly vascularized. Rupnick et al. (2002) showed that nonspecific angiogenesis inhibitors can prevent the development of obesity of mice. Kolonin et al. (2004) used in vivo phage display to isolate a peptide motif (amino sequence CKGGRAKDC) that homes to white fat vasculature. They showed that the CKGGRAKDC peptide associates with prohibitin, a multifunctional membrane protein, and thus established prohibitin as a vascular marker of adipose tissue. Targeting a proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat in mice. Resorption of established white adipose tissue and normalization of metabolism resulted in rapid obesity reversal without detectable adverse effects. Because prohibitin is also expressed in blood vessels of human white fat, the work suggested the development of targeted drugs for treatment of obese patients. Prohibitins form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria. Artal-Sanz and Tavernarakis (2009) demonstrated that the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism in C. elegans. They found that prohibitin deficiency shortened the life span of otherwise wildtype animals. Knockdown of prohibitin promoted longevity in diapause mutants or under conditions of dietary restriction. In addition, prohibitin deficiency extended the life span of animals with compromised mitochondrial functions or fat metabolism. Depletion of prohibitin influenced ATP levels, animal fat content, and mitochondrial proliferation in a genetic-background- and age-specific manner. Artal-Sanz and Tavernarakis (2009) concluded that their findings revealed a novel mechanism regulating mitochondrial biogenesis and function, with opposing effects on energy metabolism, fat utilization, and aging in C. elegans. By gel filtration, mass spectrometry, coimmunoprecipitation, and Western blot analysis of HeLa cells, Da Cruz et al. (2008) showed that prohibitin-1 and prohibitin-2 (PHB2; 610704) interacted in a 250-kD complex with SLP2 (STOML2; 608292). Knockdown of SLP2 in HeLa cells or mouse emb ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176705 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed