The Enzyme Database

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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, Gene, KEGG, MetaCyc, MEROPS, 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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [PMID: 12620104]
10.  Urban, S. and Freeman, M. Intramembrane proteolysis controls diverse signalling pathways throughout evolution. Curr. Opin. Genet. Dev. 12 (2002) 512–518. [DOI] [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. [DOI] [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. [DOI] [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) 173–182. [DOI] [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. [DOI] [PMID: 15616571]
15.  Wang, Y., Zhang, Y. and Ha, Y. Crystal structure of a rhomboid family intramembrane protease. Nature 444 (2006) 179–180. [DOI] [PMID: 17051161]
[EC 3.4.21.105 created 2005]
 
 


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