InterPro domain: IPR002610

This group of proteins contain serine peptidases belonging to the MEROPS peptidase family S54 (Rhomboid, clan ST). They are integral membrane proteins related to the Drosophila melanogaster (Fruit fly) rhomboid protein P20350 . Members of this family are found in archaea, bacteria and eukaryotes.

The D. melanogaster rhomboid protease cleaves type-1 transmembrane domains using a catalytic triad composed of serine, histidine and asparagine contributed by different transmembrane domains. It cleaves the transmembrane proteins Spitz, Gurken and Keren within their transmembrane domains to release a soluble TGFalpha-like growth factor. Cleavage occurs in the Golgi, following translocation of the substrates from the endoplasmic reticulum membrane by Star, another transmembrane protein. The growth factors are then able to activate the epidermal growth factor receptor [ 1 , 2 ].

Few substrates of mammalian rhomboid homologues have been determined, but rhomboid-like protein 2 (MEROPS S54.002) has been shown to cleave ephrin B3 [ 3 ]. Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite.

1. rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev. 4, 190-203
2. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 107, 173-82
3. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2. Biochem. Biophys. Res. Commun. 317, 244-52