rhomboid protease

Hydrolases;
Acting on peptide bonds (peptidases);
Serine endopeptidases

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

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].

1  [PMID:15684070]

Urban S, Wolfe MS.

Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity.

Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 1883-8.

Providencia stuartii, Drosophila sp.

2  [PMID:15753289]

Brossier F, Jewett TJ, Sibley LD, Urban S.

A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma.

Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 4146-51.

Toxoplasma gondii [GN:tgo]

3  [PMID:15096522]

Herlan M, Bornhovd C, Hell K, Neupert W, Reichert AS.

Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor.

J. Cell. Biol. 165 (2004) 167-73.

Saccharomyces cerevisiae [GN:sce]

4  [PMID:15047175]

Pascall JC, Brown KD.

Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2.

Biochem. Biophys. Res. Commun. 317 (2004) 244-52.

Homo sapiens [GN:hsa]

5  [PMID:14732705]

Sik A, Passer BJ, Koonin EV, Pellegrini L.

Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide.

J. Biol. Chem. 279 (2004) 15323-9.

Drosophila sp.

6  [PMID:12820957]

Urban S, Freeman M.

Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain.

Mol. Cell. 11 (2003) 1425-34.

Toxoplasma gondii [GN:tgo]

7  [PMID:12707284]

Herlan M, Vogel F, Bornhovd C, Neupert W, Reichert AS.

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) 27781-8.

Homo sapiens [GN:hsa]

8  [PMID:12774122]

McQuibban GA, Saurya S, Freeman M.

Mitochondrial membrane remodelling regulated by a conserved rhomboid protease.

Nature. 423 (2003) 537-41.

Saccharomyces cerevisiae [GN:sce]

9  [PMID:12620104]

Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, 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.

Providencia stuartii, Drosophila sp.

10 [PMID:12200155]

Urban S, Freeman M.

Intramembrane proteolysis controls diverse signalling pathways throughout evolution.

Curr. Opin. Genet. Dev. 12 (2002) 512-8.

Drosophila sp.

11 [PMID:12225666]

Urban S, Schlieper D, Freeman M.

Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids.

Curr. Biol. 12 (2002) 1507-12.

Providencia stuartii

12 [PMID:12169630]

Urban S, Lee JR, Freeman M.

A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands.

EMBO. J. 21 (2002) 4277-86.

Drosophila sp.

13 [PMID:11672525]

Urban S, Lee JR, Freeman M.

Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases.

Cell. 107 (2001) 173-82.

Homo sapiens [GN:hsa]

14 [PMID:15616571]

Lemberg MK, Menendez J, Misik A, Garcia M, Koth CM, Freeman M.

Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases.

EMBO. J. 24 (2005) 464-72.

Homo sapiens [GN:hsa], Escherichia coli [GN:eco], Bacillus subtilis [GN:bsu], Pseudomonas aeruginosa [GN:pae], Aquifex aeolicus [GN:aae], Drosophila sp., Providencia stuartii

15 [PMID:17051161]

Wang Y, Zhang Y, Ha Y.

Crystal structure of a rhomboid family intramembrane protease.

Nature. 444 (2006) 179-80.

Escherichia coli [GN:eco]