KEGG   ENZYME: 3.4.21.105Help
Entry
EC 3.4.21.105               Enzyme                                 

Name
rhomboid protease
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Serine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains
Comment
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].
History
EC 3.4.21.105 created 2005
Orthology
K02857  
rhomboid-related protein 1/2/3
K09650  
rhomboid-like protein
Genes
HSA: 
162494(RHBDL3) 54933(RHBDL2) 55486(PARL) 9028(RHBDL1)
PTR: 
453801(RHBDL1) 456773(RHBDL2) 460877(PARL) 747914(RHBDL3)
PPS: 
100972422(RHBDL1) 100981191(PARL) 100991726(RHBDL2) 100995298(RHBDL3)
GGO: 
101129399(RHBDL1) 101136818(PARL) 101140065(RHBDL2) 101145550(RHBDL3)
PON: 
100173771(PARL) 100442110(RHBDL1) 100450187(RHBDL3) 100452148(RHBDL2)
MCC: 
704652(PARL) 713926(RHBDL3) 715695 722357(RHBDL1)
MCF: 
101926657 102115426(RHBDL2) 102122957(RHBDL3) 102125336(RHBDL1)
MMU: 
214951(Rhbdl1) 230726(Rhbdl2) 246104(Rhbdl3) 381038(Parl)
RNO: 
117025(Rhbdl1) 287556(Rhbdl3) 287979(Parl) 298512(Rhbdl2)
CGE: 
100751882(Parl) 100770158(Rhbdl2) 100771192(Rhbdl1) 100772788(Rhbdl3)
HGL: 
101700571(Rhbdl1) 101707842(Rhbdl2) 101719514(Parl) 101721490(Rhbdl3)
TUP: 
102469095(RHBDL1) 102479636(RHBDL2) 102499708(PARL) 102499910(RHBDL3)
CFA: 
482466(RHBDL2) 488100(PARL) 490092(RHBDL1) 491155(RHBDL3)
AML: 
FCA: 
101091042(PARL) 101093071(RHBDL1) 101094436(RHBDL2) 101094637(RHBDL3)
PTG: 
102953926(RHBDL1) 102966303(RHBDL2) 102969628(RHBDL3) 102969917(PARL)
BTA: 
100336895(RHBDL1) 514191(PARL) 514943(RHBDL2) 535623(RHBDL3)
BOM: 
102267300(RHBDL3) 102279965(RHBDL1) 102282409(RHBDL2) 102282701(PARL)
PHD: 
102324723(PARL) 102330979(RHBDL2) 102339958(RHBDL3) 102341809(RHBDL1)
CHX: 
102170845(RHBDL2) 102173434(RHBDL1) 102186804(PARL) 102187708(RHBDL3)
OAS: 
101102026(PARL) 101110639(RHBDL1) 101115635(RHBDL3) 101117975(RHBDL2)
SSC: 
100514296(RHBDL2) 100522032(RHBDL3) 100739380(PARL) 102164926(RHBDL1)
CFR: 
102508789(RHBDL1) 102513177(RHBDL3) 102515444(PARL) 102522404(RHBDL2)
BACU: 
102997324(RHBDL1) 103010626(RHBDL3) 103012865(PARL) 103013581 103015879(RHBDL2)
LVE: 
103080294(RHBDL1) 103080823(PARL) 103090747(RHBDL2) 103091370(RHBDL3)
ECB: 
100058851(PARL) 100066958(RHBDL1) 100068889(RHBDL2) 100071775(RHBDL3)
MYB: 
102241382(RHBDL3) 102246769(PARL) 102248737(RHBDL2) 102254499(RHBDL1)
MYD: 
102757308(RHBDL2) 102765700(RHBDL1) 102774042(PARL) 102774862(RHBDL3)
PALE: 
102885710(RHBDL3) 102894455(PARL) 102895339(RHBDL1) 102897150(RHBDL2)
MDO: 
100016926(RHBDL1) 100018675(RHBDL3) 100027636(PARL) 100031939(RHBDL2)
SHR: 
100921266(RHBDL3) 100926501(PARL) 100930684(RHBDL1) 100932354(RHBDL2)
OAA: 
100078408(PARL) 100082184(RHBDL2) 100087354 100089671(RHBDL3)
GGA: 
417411(RHBDL3) 424767(PARL) 429205(RHBDL1)
MGP: 
TGU: 
FAB: 
101812184(RHBDL1) 101814172(PARL) 101816853(RHBDL3)
PHI: 
102100139(RHBDL3) 102100599(RHBDL1) 102108104(PARL)
APLA: 
101792169(RHBDL3) 101803884(PARL)
FPG: 
101910681(PARL) 101916424(RHBDL3)
FCH: 
102050957(RHBDL1) 102055499(RHBDL3) 102059074(PARL)
CLV: 
102085794(RHBDL3) 102087133(PARL) 102094909(RHBDL1)
ASN: 
102368004(RHBDL3) 102375886(RHBDL2) 102376993(PARL) 102377147(RHBDL1)
AMJ: 
102569235(PARL) 102572703(RHBDL1) 102572803(RHBDL3) 102573319(RHBDL2)
PSS: 
102448376(RHBDL2) 102448490(PARL) 102454812(RHBDL1) 102462839(RHBDL3)
CMY: 
102932324(RHBDL2) 102942181(PARL) 102943255(RHBDL1) 102945614(RHBDL3)
ACS: 
100552010(rhbdl3) 100553171(parl) 100556273(rhbdl2) 100556287
PBI: 
103050233(RHBDL1) 103052191(PARL) 103053550(RHBDL3) 103063065(RHBDL2)
XLA: 
444640(rhbdl1) 495156(rhbdl2)
XTR: 
100036610(parl) 549275(rhbdl2)
DRE: 
100887821(rhbdl1) 541485(parla) 550128(rhbdl3) 792002(rhbdl2) 792889
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
102345090(PARL) 102357284(RHBDL1) 102357617(RHBDL3) 102365369(RHBDL2)
CMK: 
BFO: 
CIN: 
SPU: 
DME: 
DPO: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
DGR: 
DMO: 
DVI: 
AGA: 
AAG: 
CQU: 
AME: 
412194(rho-7) 412319(GB16638)
NVI: 
TCA: 
657740(stet) 661151 661276 663099(rho-4)
BMOR: 
API: 
PHU: 
ISC: 
CEL: 
CBR: 
CBG14977(Cbr-rom-5) CBG18183(Cbr-rom-1)
BMY: 
LOA: 
TSP: 
SMM: 
NVE: 
HMG: 
TAD: 
CSL: 
CME: 
GSL: 
CCP: 
SCE: 
YGR101W(PCP1)
AGO: 
ERC: 
KLA: 
LTH: 
VPO: 
ZRO: 
CGR: 
NCS: 
NCAS_0E01050(NCAS0E01050)
NDI: 
NDAI_0G01180(NDAI0G01180)
TPF: 
TPHA_0D03000(TPHA0D03000)
TBL: 
TBLA_0E00580(TBLA0E00580)
TDL: 
TDEL_0F03280(TDEL0F03280)
KAF: 
KAFR_0K01640(KAFR0K01640)
PPA: 
DHA: 
PIC: 
PGU: 
SPAA: 
LEL: 
CAL: 
CTP: 
COT: 
CDU: 
CTEN: 
YLI: 
CLU: 
SMP: 
PAN: 
TTT: 
MTM: 
CTHR: 
MGR: 
TMN: 
FGR: 
NHE: 
TRE: 
MAW: 
MAJ: 
CMT: 
VAL: 
ELA: 
SSL: 
BFU: 
MBE: 
ANI: 
AFM: 
AOR: 
AOR_1_2814174(AO090005001606)
ANG: 
ANI_1_82074(An08g00670)
AFV: 
ACT: 
NFI: 
PCS: 
CIM: 
CPW: 
PBL: 
URE: 
ABE: 
TVE: 
AJE: 
PNO: 
PTE: 
BZE: 
BSC: 
BOR: 
ZTR: 
PFJ: 
BCOM: 
NPA: 
TML: 
CNE: 
CNB: 
CGI: 
TMS: 
PPL: 
DSQ: 
SHS: 
PCO: 
PSQ: 
ADL: 
FME: 
GTR: 
LBC: 
MRR: 
CCI: 
SCM: 
ABP: 
AGABI1DRAFT70511(AGABI1DRAFT_70511)
ABV: 
AGABI2DRAFT193382(AGABI2DRAFT_193382)
CPUT: 
SLA: 
UMA: 
PFP: 
MGL: 
PGR: 
MLR: 
WSE: 
MBR: 
DDI: 
DPP: 
DFA: 
TPS: 
PIF: 
EHX: 
GTT: 
NGR: 
PHE: 
 » show all
Taxonomy
Reference
1  [PMID:15684070]
  Authors
Urban S, Wolfe MS.
  Title
Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 1883-8.
  Sequence
[bsu:BSU24870]
Reference
2  [PMID:15753289]
  Authors
Brossier F, Jewett TJ, Sibley LD, Urban S.
  Title
A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 4146-51.
  Sequence
Reference
3  [PMID:15096522]
  Authors
Herlan M, Bornhovd C, Hell K, Neupert W, Reichert AS.
  Title
Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor.
  Journal
J. Cell. Biol. 165 (2004) 167-73.
Reference
4  [PMID:15047175]
  Authors
Pascall JC, Brown KD.
  Title
Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2.
  Journal
Biochem. Biophys. Res. Commun. 317 (2004) 244-52.
  Sequence
[hsa:54933]
Reference
5  [PMID:14732705]
  Authors
Sik A, Passer BJ, Koonin EV, Pellegrini L.
  Title
Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide.
  Journal
J. Biol. Chem. 279 (2004) 15323-9.
  Sequence
[hsa:55486]
Reference
6  [PMID:12820957]
  Authors
Urban S, Freeman M.
  Title
Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain.
  Journal
Mol. Cell. 11 (2003) 1425-34.
Reference
7  [PMID:12707284]
  Authors
Herlan M, Vogel F, Bornhovd C, Neupert W, Reichert AS.
  Title
Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA.
  Journal
J. Biol. Chem. 278 (2003) 27781-8.
  Sequence
[sce:YGR101W]
Reference
8  [PMID:12774122]
  Authors
McQuibban GA, Saurya S, Freeman M.
  Title
Mitochondrial membrane remodelling regulated by a conserved rhomboid protease.
  Journal
Nature. 423 (2003) 537-41.
  Sequence
[sce:YGR101W]
Reference
9  [PMID:12620104]
  Authors
Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, Pellegrini L.
  Title
The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers.
  Journal
Genome. Biol. 4 (2003) R19.
Reference
10 [PMID:12200155]
  Authors
Urban S, Freeman M.
  Title
Intramembrane proteolysis controls diverse signalling pathways throughout evolution.
  Journal
Curr. Opin. Genet. Dev. 12 (2002) 512-8.
Reference
11 [PMID:12225666]
  Authors
Urban S, Schlieper D, Freeman M.
  Title
Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids.
  Journal
Curr. Biol. 12 (2002) 1507-12.
Reference
12 [PMID:12169630]
  Authors
Urban S, Lee JR, Freeman M.
  Title
A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands.
  Journal
EMBO. J. 21 (2002) 4277-86.
Reference
13 [PMID:11672525]
  Authors
Urban S, Lee JR, Freeman M.
  Title
Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases.
  Journal
Cell. 107 (2001) 173-82.
  Sequence
Reference
14 [PMID:15616571]
  Authors
Lemberg MK, Menendez J, Misik A, Garcia M, Koth CM, Freeman M.
  Title
Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases.
  Journal
EMBO. J. 24 (2005) 464-72.
  Sequence
[bsu:BSU24870]
Reference
15 [PMID:17051161]
  Authors
Wang Y, Zhang Y, Ha Y.
  Title
Crystal structure of a rhomboid family intramembrane protease.
  Journal
Nature. 444 (2006) 179-80.
  Sequence
[eco:b3424]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
713145-02-9

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