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Information on EC 3.4.21.105 - rhomboid protease and Organism(s) Toxoplasma gondii and UniProt Accession Q6GV23
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3.4.21.105 rhomboid proteaseSpecify your search results
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argos
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glenohumeral
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The taxonomic range for the selected organisms is: Toxoplasma gondii
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains
Synonyms
rhomboid, derlin-1, rhbdd1, rhomboid protease, intramembrane protease, rhbdl2, rhbdl4, rhomboid protein, ehrom1, rho-4, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
TgROM4
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains
ROM1 of Toxoplasma gondii contains a catalytic triad consisting of asparagine, histidine, and serine residues of in transmembrane domains 2, 6, and 4
CAS REGISTRY NUMBER
COMMENTARY
713145-02-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
adhesin MIC2 + H2O
?
-
the ectodomain of Toxoplasma gondii adhesin MIC2, a type-I membrane protein is cleaved by rhomboid
-
-
?
MIC adhesin + H2O
?
-
only TgRMO5 is able to cleave MIC adhesins, it likely provides the key protease activity necessary for invasion
-
-
?
additional information
?
-
ROM1 does not play a critical role in cell invasion, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, ROM1 is required for efficient intracellular growth of the parasite, overview
-
-
?
additional information
?
-
-
ROM1 does not play a critical role in cell invasion, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, ROM1 is required for efficient intracellular growth of the parasite, overview
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of growth factor signaling, mitochondrial fusion, and parasite invasion
-
-
?
additional information
?
-
-
the enzyme proteolytically cleaves adhesin-receptor complexes during parasite invasion, overview, the enzyme is important in cell sigaling, mechanism, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
MIC adhesin + H2O
?
-
only TgRMO5 is able to cleave MIC adhesins, it likely provides the key protease activity necessary for invasion
-
-
?
additional information
?
-
ROM1 does not play a critical role in cell invasion, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, ROM1 is required for efficient intracellular growth of the parasite, overview
-
-
?
additional information
?
-
-
ROM1 does not play a critical role in cell invasion, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, ROM1 is required for efficient intracellular growth of the parasite, overview
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of growth factor signaling, mitochondrial fusion, and parasite invasion
-
-
?
additional information
?
-
-
the enzyme proteolytically cleaves adhesin-receptor complexes during parasite invasion, overview, the enzyme is important in cell sigaling, mechanism, overview
-
-
?
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
TgROM5 is localized to the cell surface, primarily at the posterior of the parasite
additional information
Toxoplasma gondii contains six rhomboids that are expressed in different life cycle stages and localized to different cellular compartments
additional information
-
Toxoplasma gondii contains six rhomboids that are expressed in different life cycle stages and localized to different cellular compartments
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
TgROM5 is localized to the cell surface, primarily at the posterior of the parasite
-
the enzyme is an intramembrane serine protease, intramembrane rhomboid topology, modeling, overview
Toxoplasma gondii contains six rhomboids that are expressed in different life cycle stages and localized to different cellular compartments, ROM1 is not released onto the parasite surface during cell invasion, subcellular localization of HA9-tagged ROM1 in intracellular parasites, overview
-
N-terminal domain is responsible for subcellular localisation of TgROM1, in particular the sequence FPHF is essential (amino acids 54-57)
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
both isoforms ROM4 and ROM5 are dispensable for parasite survival. Shedding of micronemal proteins and invasion are not altered in the absence of ROM5, but this protease is responsible for the residual cleavage of apical membrane antigen AMA1, is able to cleave other apical membrane antigen family members and exhibits a detectable contribution to invasion in the absence of ROM4
malfunction
suppression of TgROM4 leads to decreased release of the adhesin MIC2 into the supernatant and concomitantly increases the surface expression of this and a subset of other adhesins. Suppression of TgROM4 results in disruption of normal gliding, with the majority of parasites twirling on their posterior ends. Parasites lacking TgROM4 bind better to host cells, but lose the ability to apically orient therefore invasion is severely impaired
physiological function
physiological function
TgROM4 is involved in shedding of micronemal proteins from the cell surface. Down regulation of TgROM4 disrupts the normal apical-posterior gradient of adhesins that is important for efficient cell motility and invasion of host cells by Toxoplasma gondii
physiological function
deletion of isoform ROM4 blocks the shedding of adhesins such as MIC2 (microneme protein 2), causing them to accumulate on the surface of extracellular parasites. Increased surface adhesins lead to nonproductive attachment, altered gliding motility, impaired moving junction formation, and reduced invasion efficiency. ROM4 is the primary protease involved in adhesin processing and host cell invasion. Triple mutants lacking all isoforms ROM1/ROM4/ROM5 are viable and MIC2 is still efficiently removed from the surface of invaded mutant parasites, implying the existence of ROM-independent mechanisms for adhesin removal during invasion
physiological function
parasites lacking isoform ROM4 predominantly engage in twirling motility and exhibit enhanced attachment and impaired invasion, whereas intracellular growth and egress are not affected. The substrates microneme proteins MIC2 and MIC6 are not cleaved and accumulate on the rom4 -knockout parasite surface
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). RHBL5_TOXGO
841
6
92102
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
determination and classification of intramembrane rhomboid topology, modeling, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of Escherichia coli GlpG consists of a 6-transmembrane domain topology
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F36A/F37A
-
mutant is still targeted efficiently to the Golgi compartment, indicating that in TgROM2 there are two crucial signal elements responsible for Golgi targeting
F36A/F37A/D256A/R257A
-
Golgi localisation is not affected in the mutant protein
H2541X
-
using mutagenesis it is shown that His254 is catalytically essential
S201X
-
using mutagenesis it is shown that Ser201 is catalytically essential
additional information
additional information
construction of ROM1-knockout mutant, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, overview
additional information
-
construction of ROM1-knockout mutant, ROM1-deficient parasites are outcompeted by wild-type Toxoplasma gondii, the ROM1-deficient parasites show only modest decrease in invasion but replicate more slowly than wild-type cells, overview
additional information
-
by analyzing chimeric proteins it is shown that the N-terminal domain of TgROM2 is sufficient to confer Golgi localisation to related ROM proteins that are normally localised to the plasma membrane or to micronemes. F36 and F37 are crucial in this targeting process
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type HA9-tagged ROM1 and of muant ROM1 in the parasites, repression of Tet-regulatable HA9-ROM1 expression in the presence of Atc, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
TgROM5 is able to cleave MIC adhesins. It likely provides the key protease activity necessary for invasion. The enzyme TgROM5 offers a target for therapeutic intervention against invasion by the deadly pathogen Toxoplasma gondii
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Brossier, F.; Jewett Travis, J.; Sibley, L.D.; Urban, S.
A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma
Proc. Natl. Acad. Sci. USA
102
4146-4151
2005
Toxoplasma gondii, Toxoplasma gondii TgROM2, Toxoplasma gondii TgROM1, Toxoplasma gondii TgROM3, Toxoplasma gondii TgROM5, Toxoplasma gondii TgROM4
Brossier, F.; Starnes, G.L.; Beatty, W.L.; Sibley, L.D.
Microneme rhomboid protease TgROM1 is required for efficient intracellular growth of Toxoplasma gondii
Eukaryot. Cell
7
664-674
2008
Toxoplasma gondii (Q695U0), Toxoplasma gondii
Urban, S.
Rhomboid proteins: conserved membrane proteases with divergent biological functions
Genes Dev.
20
3054-3068
2006
Arabidopsis thaliana, Bacillus subtilis, Saccharomyces cerevisiae, Drosophila melanogaster, Escherichia coli, Homo sapiens, Providencia stuartii, Toxoplasma gondii
Lemberg, M.K.; Freeman, M.
Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases
Genome Res.
17
1634-1646
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus, Plasmodium falciparum, Toxoplasma gondii, Escherichia coli (P09391), Providencia stuartii (P46116), Bacillus subtilis (P54493), Pseudomonas aeruginosa (Q9HZC2)
Sheiner, L.; Dowse, T.J.; Soldati-Favre, D.
Identification of trafficking determinants for polytopic rhomboid proteases in Toxoplasma gondii
Traffic
9
665-677
2008
Toxoplasma gondii
Buguliskis, J.S.; Brossier, F.; Shuman, J.; Sibley, L.D.
Rhomboid 4 (ROM4) affects the processing of surface adhesins and facilitates host cell invasion by Toxoplasma gondii
PLoS Pathog.
6
e1000858
2010
Toxoplasma gondii (Q695T8), Toxoplasma gondii
Ha, Y.
Structure and mechanism of intramembrane protease
Semin. Cell Dev. Biol.
20
240-250
2009
Saccharomyces cerevisiae, Drosophila melanogaster, Plasmodium falciparum, Toxoplasma gondii, Escherichia coli (P09391)
Shen, B.; Buguliskis, J.; Lee, T.; David Sibley, L.
Functional analysis of rhomboid proteases during Toxoplasma invasion
mBio
5
e01795
2014
Toxoplasma gondii (Q695T8), Toxoplasma gondii
Rugarabamu, G.; Marq, J.B.; Guerin, A.; Lebrun, M.; Soldati-Favre, D.
Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to micronemal protein protease 1 activity during invasion
Mol. Microbiol.
97
244-262
2015
Toxoplasma gondii (Q695T8), Toxoplasma gondii (Q6GV23), Toxoplasma gondii
EXTERNAL LINKS (specific for EC-Number 3.4.21.105)
Transporter Classification Database (TCDB): 9.B.104.4.1, 9.B.104.2.1, 9.B.104.1.1, 9.B.104.1.6, 9.B.104.1.7
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