Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2008) Nucleic Acids Res , doi:10.1093/nar/gkn808

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PHB prohibitin homologues

There are 2700 PHB domains in 2700 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PHB domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PHB domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Steglich G, Neupert W, Langer T
  • Prohibitins regulate membrane protein degradation by the m-AAA protease in mitochondria.
  • Mol Cell Biol. 1999; 19: 3435-42
  • Display abstract

  • Prohibitins comprise a protein family in eukaryotic cells with potential roles in senescence and tumor suppression. Phb1p and Phb2p, members of the prohibitin family in Saccharomyces cerevisiae, have been implicated in the regulation of the replicative life span of the cells and in the maintenance of mitochondrial morphology. The functional activities of these proteins, however, have not been elucidated. We demonstrate here that prohibitins regulate the turnover of membrane proteins by the m-AAA protease, a conserved ATP-dependent protease in the inner membrane of mitochondria. The m-AAA protease is composed of the homologous subunits Yta10p (Afg3p) and Yta12p (Rca1p). Deletion of PHB1 or PHB2 impairs growth of Deltayta10 or Deltayta12 cells but does not affect cell growth in the presence of the m-AAA protease. A prohibitin complex with a native molecular mass of approximately 2 MDa containing Phb1p and Phb2p forms a supercomplex with the m-AAA protease. Proteolysis of nonassembled inner membrane proteins by the m-AAA protease is accelerated in mitochondria lacking Phb1p or Phb2p, indicating a negative regulatory effect of prohibitins on m-AAA protease activity. These results functionally link members of two conserved protein families in eukaryotes to the degradation of membrane proteins in mitochondria.

• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the PHB domain.

  Protein	Disease
  Prohibitin (SRS)(SMART)	OMIM:176705: Breast cancer, sporadic
  Podocin (SRS)(SMART)	OMIM:600995: Nephrotic syndrome, idiopathic, steroid-resistant OMIM:604766: Nephrotic syndrome, steroid-resistant OMIM:600995:

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 71.43 map04910 Insulin signaling pathway 14.29 map00780 Biotin metabolism 14.29 map00310 Lysine degradation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PHB domain which could be assigned to a KEGG orthologous group, and not all proteins containing PHB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of PHB domains in PDB

  PDB code	Main view	Title
  2rpb
  3bk6		Crystal structure of a core domain of stomatin from pyrococcus horikoshii

• Links (links to other resources describing this domain)

• PFAM	Band_7
  INTERPRO	IPR001107
  PROSITE	BAND_7