The rhomboid-like superfamily: molecular mechanisms and biological roles.

  title={The rhomboid-like superfamily: molecular mechanisms and biological roles.},
  author={Matthew Freeman},
  journal={Annual review of cell and developmental biology},
  • M. Freeman
  • Published 6 October 2014
  • Biology
  • Annual review of cell and developmental biology
The rhomboid proteases were first discovered as regulators of Drosophila EGF receptor signaling; soon after, it was recognized that they represented the founder members of a widespread family of intramembrane serine proteases conserved in all kingdoms. More recently still, the family was promoted to a superfamily, encompassing a wide variety of distantly related proteins. One of the surprises has been that many members of the rhomboid-like superfamily are not active proteases. Given the size of… 

The complex life of rhomboid pseudoproteases

The mechanism(s) of action) and roles of rhomboid pseudoproteases in mammalian physiology are highlighted, which, quite paradoxically among pseudoenzymes, is understood much better than active rhomboids.

nactive rhomboid proteins : New mechanisms with implications in ealth and disease

This work distil the ndoplasmic reticulum-associated protein and highlights how loss of proteolytic activity was followed in evolution by impressive functional diversification, enabling these pseudoproteases to fulfill crucial roles within the secretory pathway, including protein degradation, trafficking regulation, and inflammatory signaling.

Rhomboid proteases in human disease: Mechanisms and future prospects.

Novel functions of inactive rhomboid proteins in immunity and disease

The current understanding of iRhom biology, their implications in autoimmune pathologies, and their potential as therapeutic targets are discussed.

The molecular, cellular and pathophysiological roles of iRhom pseudoproteases

What is known about iRhom molecular mechanisms and relevance in known pathologies is discussed, and it seems likely that as the involvement of iRhoms in human diseases is increasingly recognized, they will become the focus of pharmaceutical interest.

The role of rhomboid superfamily members in protein homeostasis: Mechanistic insight and physiological implications.

Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα

It is proposed that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling, and is identified as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes.



Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases.

Despite the complex classification of rhomboids, the data suggest that a rhomboid-type intramembrane protease may have been present in the last eukaryotic common ancestor.

Structure and Mechanism of Rhomboid Protease*

Progress in crystallographic analysis of the Escherichia coli rhomboid protease GlpG in complex with inhibitors has provided new insights into the catalytic mechanism of the protease and its conformational change.

Bioinformatics perspective on rhomboid intramembrane protease evolution and function.

Sampling the membrane: function of rhomboid-family proteins.

Untangling structure-function relationships in the rhomboid family of intramembrane proteases.

Role of rhomboid proteases in bacteria.

  • P. Rather
  • Biology
    Biochimica et biophysica acta
  • 2013