IUBMB Enzyme Nomenclature

EC 3.4.21.105

Accepted name: rhomboid protease

Reaction: Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains

Comments: These endopeptidases are multi-spanning membrane proteins. Their catalytic site is embedded within the membrane and they cleave type-1 transmembrane domains. A catalytic dyad is involved in proteolysis rather than a catalytic triad, as was thought previously [14]. They are important for embryo development in Drosophila melanogaster. Rhomboid is a key regulator of EGF receptor signalling and is responsible for cleaving Spitz, the main ligand of the Drosophila EGF receptor pathway. Belongs in peptidase family S54. Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite. Rhomboids are widely conserved from bacteria to archaea to humans [9,13].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 713145-02-9

References:

1. Urban, S. and Wolfe, M.S. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc. Natl. Acad. Sci. USA 102 (2005) 1883-1888. [PMID: 15684070]

2. Brossier, F., Jewett, T.J., Sibley, L.D. and Urban, S. A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc. Natl. Acad. Sci. USA 102 (2005) 4146-4151. [PMID: 15753289]

3. Herlan, M., Bornhovd, C., Hell, K., Neupert, W. and Reichert, A.S. Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor. J. Cell Biol. 165 (2004) 167-173. [PMID: 15096522]

4. Pascall, J.C. and Brown, K.D. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL 2. Biochem. Biophys. Res. Commun. 317 (2004) 244–252. [PMID: 15047175]

5. Sik, A., Passer, B.J., Koonin, E.V. and Pellegrini, L. Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pβ, a nuclear-targeted peptide. J. Biol. Chem. 279 (2004) 15323-15329. [PMID: 14732705]

6. Urban, S. and Freeman, M. Substrate specificity of Rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol. Cell 11 (2003) 1425-1434. [PMID: 12820957]

7. Herlan, M., Vogel, F., Bornhovd, C., Neupert, W. and Reichert, A.S. Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J. Biol. Chem. 278 (2003) 27781-27788. [PMID: 12707284]

8. McQuibban, G.A., Saurya, S. and Freeman, M. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 423 (2003) 537-541. [PMID: 12774122]

9. Koonin, E.V., Makarova, K.S., Rogozin, I.B., Davidovic, L., Letellier, M.C. and Pellegrini, L. The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol. 4 (2003) R19 only. [PMID: 12620104]

10. Urban, S. and Freeman, M. Intramembrane proteolysis controls diverse signalling pathways throughout evolution. Curr. Opin. Genet. Dev. 12 (2002) 512-518. [PMID: 12200155]

11. Urban, S., Schlieper, D. and Freeman, M. Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic Rhomboids. Curr. Biol. 12 (2002) 1507-1512. [PMID: 12225666]

12. Urban, S., Lee, J.R. and Freeman, M. A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF-like ligands. EMBO J. 21 (2002) 4277-4286. [PMID: 12169630]

13. Urban, S., Lee, J.R. and Freeman, M. Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 107 (2001) 173-sh;182. [PMID: 11672525]

14. Lemberg, M.K., Menendez, J., Misik, A., Garcia, M., Koth, C.M. and Freeman, M. Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases. EMBO J. 24 (2005) 464-472. [PMID: 15616571]

15. Wang, Y., Zhang, Y. and Ha, Y. Crystal structure of a rhomboid family intramembrane protease. Nature 444 (2006) 179-180. [PMID: 17051161]

[EC 3.4.21.105 created 2005]


Return to EC 3.4.21 home page
Return to EC 3.4 home page
Return to EC 3 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page