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Information on EC 3.4.24.85 - S2P endopeptidase
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EC Tree
3.4.24.85 S2P endopeptidaseSpecify your search results
Word Map
- 3.4.24.85
- cholesterol
-
srebps
- triglyceride
- peroxisome
- lipoprotein
-
lipogenesis
- srebp-1c
-
lipogenic
-
proliferator-activated
- steatosis
- adipose
- obesity
- acetyl-coa
-
high-fat
- adipocyte
-
desaturase
- hepatocytes
-
low-density
- carnitine
-
obese
- stearoyl-coa
-
amp-activated
-
diet-induced
-
site-1
- proliferator
-
hfd-induced
-
cleavage-activating
-
nonalcoholic
- adiponectin
- hyperlipidemia
- nafld
-
stearoyl
-
forespore
-
presenilins
-
niemann-pick
-
3-hydroxy-3-methylglutaryl
- sigmak
- gamma-secretase
-
membrane-embedded
- atf6
- rhomboid
-
anti-adipogenic
- medicine
-
chrebp
- acaca
- synthesis
-
palmitoyltransferase-1
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site DRSR_ILL_483-/-CVLTFLCLSFNPLTSLLQWGGA, in which the membrane-spanning segment is underlined. The residues NP (bold), 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.
Synonyms
sterol regulatory element binding protein, spoivfb, site-2 protease, intramembrane-cleaving protease, i-clip, sll0528, slr0643, sterol-regulated protease, site-2-protease, rv2869c, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Eep
HurP
intramembrane-cleaving protease
proteinase, sterol regulatory element-binding protein
-
-
-
-
RasP
S2P
S2P protease
site-1 protease
-
-
-
-
site-2 protease
sll0528
SREBP cleavage activity
-
-
-
-
SREBP cysteine proteinase
-
-
-
-
SREBP proteinase
-
-
-
-
SREBP-1 proteinase
-
-
-
-
SREBP-2 proteinase
sterol regulatory element-binding proteinase
-
-
-
-
sterol-regulated protease
-
-
-
-
YaeL
site-2 protease
-
-
-
-
SREBP-2 proteinase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site DRSR_ILL_483-/-CVLTFLCLSFNPLTSLLQWGGA, in which the membrane-spanning segment is underlined. The residues NP (bold), 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
167140-48-9
-
752251-31-3
-
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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
ATF-6 + H2O
?
-
endoplasmic reticulum membrane-anchored transcription factor, sequential processing by enzyme and S1P endopeptidase. Bulky ATF6 luminal domain blocks cleavage by enzyme, cleavage by S1P endopeptidase reduces the size of the luminal domain and prepares for hydrolysis by enzyme
-
-
?
beta-lactamase signal peptide + H2O
?
-
cleaves within the hydrophobic core at Pro12-Phe13. Cleavage of signal peptide requires a preceding processing of preproteins by Lep
-
-
?
CED-9 + H2O
?
-
artificial protein substrate, Caenorhabditis elegans protein 9, homolog to human Bcl-2
-
-
?
membrane-bound inactive transcription factor fragment bZIP28X1 + H2O
?
-
transcription factor bZIP28 is cleaved within the transmembrane domain, and the N-terminal portion containing the bZIP domain is released from the membrane to translocate into the nucleus, where it activates the ER stress-responsive genes
-
-
?
membrane-bound inactive transcription factor fragment bZIP28X2 + H2O
?
-
transcription factor bZIP28 is cleaved within the transmembrane domain, and the N-terminal portion containing the bZIP domain is released from the membrane to translocate into the nucleus, where it activates the ER stress-responsive genes
-
-
?
PodJS + H2O
?
-
truncated form of transmembrane protein PodJ which provides the spatial cues for biogenesis of several polar organelles. Enzyme cleaves within or near the transmembrane segment of PodJS releasing it into cytoplasm for complete proteolysis
-
-
?
pro-deltaK protein + H2O
deltaK protein + N-terminal fragment of 20 amino acids of pro-deltaK protein
-
-
-
-
?
ATF6 + H2O
?
-
cleavage in site-2 is required for induction of IRE1-alpha and ER-stress activated target genes
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
Halalkalibacterium halodurans
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
cleavage at site-2 between 484-485 aa of SREBP cannot occur without prior cleavage at site-1 and is dependent on 478DRSR sequence
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
-
-
?
additional information
?
-
YaeL is required for the activation of sigma factor E in response to stress by site-2 cleavage of RseA that acts as an anti-sigma factor E
-
-
?
additional information
?
-
-
YaeL is required for the activation of sigma factor E in response to stress by site-2 cleavage of RseA that acts as an anti-sigma factor E
-
-
?
additional information
?
-
SREBP asparagine-495 and proline-496 seem to be necessary for cleavage by S2P, and it is conserved in all known SREBPs, the movement of the NP sequence within the transmembrane domain does not eliminate cleavage, nor does it change the site of cleavage
-
-
?
additional information
?
-
in most cases, substrate cleavage by the enzyme requires a preceding truncation of the same substrate by another aqueous protease
-
-
?
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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
beta-lactamase signal peptide + H2O
?
-
cleaves within the hydrophobic core at Pro12-Phe13. Cleavage of signal peptide requires a preceding processing of preproteins by Lep
-
-
?
membrane-bound inactive transcription factor fragment bZIP28X1 + H2O
?
-
transcription factor bZIP28 is cleaved within the transmembrane domain, and the N-terminal portion containing the bZIP domain is released from the membrane to translocate into the nucleus, where it activates the ER stress-responsive genes
-
-
?
membrane-bound inactive transcription factor fragment bZIP28X2 + H2O
?
-
transcription factor bZIP28 is cleaved within the transmembrane domain, and the N-terminal portion containing the bZIP domain is released from the membrane to translocate into the nucleus, where it activates the ER stress-responsive genes
-
-
?
PodJS + H2O
?
-
truncated form of transmembrane protein PodJ which provides the spatial cues for biogenesis of several polar organelles. Enzyme cleaves within or near the transmembrane segment of PodJS releasing it into cytoplasm for complete proteolysis
-
-
?
pro-deltaK protein + H2O
deltaK protein + N-terminal fragment of 20 amino acids of pro-deltaK protein
-
-
-
-
?
SREBP NH2-522 fragment + H2O
NH2-484 fragment + 38 aa fragment
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-N-(2-[[3-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)propyl]sulfanyl]phenyl)-3-phenylprop-2-enamide
1-[(benzoylamino)methyl]-1-[3-(benzylsulfanyl)-1-methoxy-1-oxopropan-2-yl]-4-[(benzylsulfanyl)methyl]-2,5-dioxoimidazolidin-1-ium
3-(butan-2-yl)-8-[3-[(4-fluorophenyl)sulfanyl]propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
cholesterol
inhibits the first cleavage of SREBP and indirectly S2P cleavage
(2E)-N-(2-[[3-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)propyl]sulfanyl]phenyl)-3-phenylprop-2-enamide
-
-
(2E)-N-(2-[[3-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)propyl]sulfanyl]phenyl)-3-phenylprop-2-enamide
-
1,10-phenanthroline
-
1,10-phenanthroline specifically inhibits substrate cleavage in a concentration-dependent manner
1-[(benzoylamino)methyl]-1-[3-(benzylsulfanyl)-1-methoxy-1-oxopropan-2-yl]-4-[(benzylsulfanyl)methyl]-2,5-dioxoimidazolidin-1-ium
-
-
1-[(benzoylamino)methyl]-1-[3-(benzylsulfanyl)-1-methoxy-1-oxopropan-2-yl]-4-[(benzylsulfanyl)methyl]-2,5-dioxoimidazolidin-1-ium
-
3-(butan-2-yl)-8-[3-[(4-fluorophenyl)sulfanyl]propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
-
-
3-(butan-2-yl)-8-[3-[(4-fluorophenyl)sulfanyl]propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
-
7,8-dimethoxy-1,2,3,11a-tetrahydro-5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine-5,11-dione
-
analog of nelfinavir, inhibits cleavage of artificial protein substrate CED-9 in an in vitro proteolysis assay. Inhibits castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of site-2 protease cleavage activity
7,8-dimethoxy-1,2,3,11a-tetrahydro-5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine-5,11-dione
-
-
7,8-dimethoxy-1,2,3,11a-tetrahydro-5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine-5,11-dione
-
methyl 4-[[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutyl]sulfanyl]benzoate
-
-
methyl 4-[[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutyl]sulfanyl]benzoate
-
nelfinavir
-
nelfinavir and its analogs inhibit cleavage of artificial protein substrate CED-9 in an in vitro proteolysis assay. Nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of site-2 protease cleavage activity
nelfinavir
-
nelfinavir is a more potent inhibitor of CED-9 protein cleavage than 1,10-phenanthroline
nelfinavir
nelfinavir is a more potent inhibitor of CED-9 protein cleavage than 1,10-phenanthroline
additional information
-
SpoIVFB is held inactive by two other integral-membrane proteins, SpoIVFA and BofA
-
additional information
-
gamma-sectretase inhibitor LY411575 is not inhibitory for enzyme
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
thapsigargin
-
cells treated with thapsigargin exhibit proteolytic cleavage of SREBP-2
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
validation of cellular assay for enzyme and S1P endopeptidase activity based on release of N-terminus of sterol regulatory element binding protein driving the expression of a luciferase reporter gene
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
CHO-K1 wild type and M19 S2P deficient cell lines
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
enzyme is unifirmly distributed around the cell and present throughout the cell cycle
-
brenda
transmembrane protein YaeL has the consensus metal-binding site
-
brenda
-
colocalization with S1P endopepetidase in cis/medial Golgi
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
after heat treatment at 44°C, the enzyme knockout mutant cannot grow at all, whereas the wild type recovers from thermal damage quickly
malfunction
an enzyme knockout mutant is more sensitive to 120 mM ammonium chloride than the wild type
malfunction
-
enzyme gene ablation is compatible with parasite replication and stage conversion but results in reduced parasite development in late liver stages and in the asexual intra-erythrocytic cycle
metabolism
-
activation of the extracytoplasmic function sigma factor sigmaP by beta-lactams in Bacillus thuringiensis requires the site-2 protease RasP
metabolism
-
activation of the extracytoplasmic function sigma factor sigmaP by beta-lactams in Bacillus thuringiensis requires the site-2 protease RasP
-
physiological function
-
HurP is essential for heme-dependent induction of bhuR and downstream genes
physiological function
-
RasP is involved in transmembrane stress signal transduction
physiological function
-
RseP introduces a cleavage into signal peptides after their signal peptidase-mediated liberation from preproteins. The enzyme is involved in degradation of remnant signal peptides left in the bacterial cytoplasmic membrane
physiological function
-
the enzyme is involved in activation of the crucial membrane-associated transcription factors deltaK during sporulation
physiological function
-
the enzyme is involved in the feedback regulation of sterol and fatty acid synthesis and uptake by controlling the activity of transcription factors, sterol regulatory element binding proteins. Through the S2P cascade, the cholesterol feedback pathway in humans is stringently regulated
physiological function
-
the enzyme is involved in the production of pheromone cAD1, cPD1, and cCF10, and inhibitor peptide iAD1 and iCF10.The enzyme processes the sex pheromone and inhibitor precursors as they pass through the cell membrane
physiological function
-
cells defective in the site-2 protease gene have remarkably higher level of superoxide and elevated rates of cell death than wild-type CHO cells. Lack of the site-2 proease gene leads to cells more vulnerable to oxidative stress. Compared with wild-type CHO cells, mutant cells have higher nicotinamide adenine dinucleotide phosphate oxidase activity and lower paraoxonase-2 expression
physiological function
gene product is essential for growth. A partially segregated mutant displays defective acid acclimation to pH 6.5. Early acid acclimation to pH 6.5 in the wild-type strain includes upregulation of sigH, hik16 and hik35 and downregulation of pcrR and sigG, as well as downregulation of porins and upregulation of inorganic carbon and nitrogen transporters. The inability of the mutant strain to survive at pH 6.5 is related to defective photosynthesis and excess expression of NADH dehydrogenase, together with excessive upregulation of carbon transporter and repression of nitrogen transporter and metabolism genes. Slr0643 disruption and expression of the sigH operon are closely related
physiological function
knock-out of sll0528 gene increases Synechocystis sp. PCC 6803 sensitivity to salt, cold and hyperosmotic stress, as revealed by retarded growth, reduced pigments and disrupted photosystems
physiological function
loss-of-function mutant confers high sensitivity to abscisic acid during seed germination. Site-2 protease desensitizes abscisic acid signaling during seed germination through regulating the activation of the membrane-associated transcription factor bZIP17 and therefore controlling the expression level of genes encoding negative regulators of abscisic acid signaling
physiological function
-
the enzyme is required for resistance to beta-lactams
physiological function
-
the enzyme is the molecular target for baicalin in inducing endoplasmic reticulum stress-mediated hepatocellular carcinoma cell apoptosis
physiological function
the enzyme plays an important role in heat acclimation
physiological function
the enzyme plays an important role in the acclimation to ammonium stress in Synechocystis sp. PCC6803
physiological function
-
the enzyme is required for resistance to beta-lactams
-
Show AA Sequence and Transmembrane Helices (1305 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 45000, triple HA epitope-tagged enzyme, calculated from amino acid sequence
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
regulatory CBS domain pair of the enzyme in the apo and nucleotide-bound form, sitting drop vapor diffusion method, using 0.1 M Bis-Tris pH 6.5, 0.2 M (NH4)2SO4, 20% (w/v) PEG 3350
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H22F
D467N
mutation of aspartate abolish activity suggesting that is the third residue that coordinates the zinc active site of S2P
H54A/D148A
-
mutant exhibits markedly compromised protease activity
additional information
additional information
M19 mutant cell line of CHO-K1 cells with no s2p activity
additional information
mutants in any of the histidines for phenylalanine or glutamic acid for alanine of the consensus metal-binding site abolished activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography, Strep-Tactin column chromatography, and Superdex S200 gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli C43 (DE3) cells for full-length protein and BL21 (DE3) pLysS (DE3) for the CBS domain
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
induction of sll0528 gene expression is observed under salt, cold and hyperosmotic stress. The gene is induced to a much smaller extent by high light and mixotrophic growth with glucose
oxidative stress significantly up-regulates site-2 protease expression in CHO cells
-
wild-type displays transient induction after transfer from pH 7.5 to 6.5
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of site-2 protease cleavage activity. This leads to accumulation of precursors of sterol regulatory element-binding protein SREBP-1 and activating transcription factor ATF6, and development of insufficient reserves of their transcriptionally-active forms
synthesis
in absence of cholesterol, SREBP double cleavage leads to activation of transcription of genes encoding multiple enzymes of the cholesterol biosynthetic pathway
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rawson, R.; Zelenski, N.; Nijhawan, D.; Ye, J.; Sakai, J.; Hasan, M.; Chang, T.; Brown, M.; Goldstein, J.
Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs
Mol. Cell
1
47-57
1997
Homo sapiens (O43462), Cricetulus griseus (O54862)
brenda
Zelenski, N.; Rawson, R.; Brown, M.; Goldstein, J.
Membrane topology of S2P, a protein required for intramembranous cleavage of sterol regulatory element-binding proteins
J. Biol. Chem.
274
21973-21980
1999
Homo sapiens (O43462)
brenda
Brown, M.; Ye, J.; Rawson, R.; Goldstein, J.
Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans
Cell
100
391-398
2000
Homo sapiens (O43462)
brenda
Ye, J.; Dav, U.; Grishin, N.; Goldstein, J.; Brown, M.
Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease
Proc. Natl. Acad. Sci. USA
97
5123-5128
2000
Homo sapiens (O43462)
brenda
Kanehara, K.; Akiyama, Y.; Ito, K.
Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli
Gene
281
71-79
2001
Escherichia coli (P0AEH1), Escherichia coli
brenda
Kanehara, K.; Ito, K.; Akiyama, Y.
YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA
Genes Dev.
16
2147-2155
2002
Escherichia coli (P0AEH1), Escherichia coli
brenda
Lee, K.; Tirasophon, W.; Shen, X.; Michalak, M.; Prywes, R.; Okada, T.; Yoshida, H.; Mori, K.; Kaufman, R.
IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
Genes Dev.
16
452-466
2002
Cricetulus griseus
brenda
Dev, K.K.; Chatterjee, S.; Osinde, M.; Stauffer, D.; Morgan, H.; Kobialko, M.; Dengler, U.; Rueeger, H.; Martoglio, B.; Rovelli, G.
Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals
Eur. J. Pharmacol.
540
10-17
2006
Chlorocebus aethiops
brenda
Shen, J.; Prywes, R.
Dependence of site-2 protease cleavage of ATF6 on prior site-1 protease digestion is determined by the size of the luminal domain of ATF6
J. Biol. Chem.
279
43046-43051
2004
Homo sapiens
brenda
Chen, J.C.; Viollier, P.H.; Shapiro, L.
A membrane metalloprotease participates in the sequential degradation of a Caulobacter polarity determinant
Mol. Microbiol.
55
1085-1103
2005
Caulobacter vibrioides
brenda
Robichon, C.; Dugail, I.
De novo cholesterol synthesis at the crossroads of adaptive response to extracellular stress through SREBP
Biochimie
89
260-264
2007
Schizosaccharomyces pombe
brenda
Urban, S.; Shi, Y.
Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases
Curr. Opin. Struct. Biol.
18
432-441
2008
Methanocaldococcus jannaschii (Q57837)
brenda
Bartz, R.; Sun, L.P.; Bisel, B.; Wei, J.H.; Seemann, J.
Spatial separation of Golgi and ER during mitosis protects SREBP from unregulated activation
EMBO J.
27
948-955
2008
Rattus norvegicus
brenda
Colgan, S.M.; Tang, D.; Werstuck, G.H.; Austin, R.C.
Endoplasmic reticulum stress causes the activation of sterol regulatory element binding protein-2
Int. J. Biochem. Cell Biol.
39
1843-1851
2007
Homo sapiens
brenda
King-Lyons, N.D.; Smith, K.F.; Connell, T.D.
Expression of hurP, a gene encoding a prospective site 2 protease, is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica
J. Bacteriol.
189
6266-6275
2007
Bordetella bronchiseptica, Escherichia coli, Vibrio cholerae serotype O1, Bordetella bronchiseptica RB50
brenda
Makinoshima, H.; Glickman, M.S.
Site-2 proteases in prokaryotes: regulated intramembrane proteolysis expands to microbial pathogenesis
Microbes Infect.
8
1882-1888
2006
Bacillus subtilis, Caulobacter vibrioides, Escherichia coli, Enterococcus faecalis, Mycobacterium tuberculosis, Vibrio cholerae serotype O1
brenda
Kinch, L.N.; Ginalski, K.; Grishin, N.V.
Site-2 protease regulated intramembrane proteolysis: Sequence homologs suggest an ancient signaling cascade
Protein Sci.
15
84-93
2006
Synechocystis sp., Arabidopsis thaliana, Halalkalibacterium halodurans, Caenorhabditis elegans, Deinococcus radiodurans, Drosophila melanogaster, Escherichia coli, Giardia intestinalis, Halobacterium sp., Homo sapiens, Methanothermobacter thermautotrophicus, Mycobacterium leprae, Plasmodium falciparum, Pyrobaculum aerophilum, Thermoplasma volcanium, Thermotoga maritima, Treponema pallidum
brenda
Feng, L.; Yan, H.; Wu, Z.; Yan, N.; Wang, Z.; Jeffrey, P.D.; Shi, Y.
Structure of a site-2 protease family intramembrane metalloprotease
Science
318
1608-1612
2007
Methanocaldococcus jannaschii
brenda
Chen, G.; Zhang, X.
New insights into S2P signaling cascades: regulation, variation and conservation
Protein Sci.
19
2015-2030
2010
Bacillus subtilis, Bordetella bronchiseptica, Caulobacter vibrioides, Cryptococcus neoformans, Enterococcus faecalis, Escherichia coli, Homo sapiens, Methanocaldococcus jannaschii, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus uberis
brenda
Saito, A.; Hizukuri, Y.; Matsuo, E.; Chiba, S.; Mori, H.; Nishimura, O.; Ito, K.; Akiyama, Y.
Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria
Proc. Natl. Acad. Sci. USA
108
13740-13745
2011
Bacillus subtilis, Escherichia coli
brenda
Guan, M.; Fousek, K.; Chow, W.A.
Nelfinavir inhibits regulated intramembrane proteolysis of sterol regulatory element binding protein-1 and activating transcription factor 6 in castration-resistant prostate cancer
FEBS J.
279
2399-2411
2012
Homo sapiens
brenda
Lei, H.; Chen, G.; Wang, Y.; Ding, Q.; Wei, D.
Sll0528, a site-2-protease, is critically involved in cold, salt and hyperosmotic stress acclimation of Cyanobacterium Synechocystis sp. PCC 6803
Int. J. Mol. Sci.
15
22678-22693
2014
Synechocystis sp. (Q55518), Synechocystis sp.
brenda
Zhang, X.; Chen, G.; Qin, C.; Wang, Y.; Wei, D.
Slr0643, an S2P homologue, is essential for acid acclimation in the cyanobacterium Synechocystis sp. PCC 6803
Microbiology
158
2765-2780
2012
Synechocystis sp. (Q55722), Synechocystis sp.
brenda
Zhou, S.; Sun, L.; Valdes, A.; Engstrm, P.; Song, Z.; Lu, S.; Liu, J.
Membrane-associated transcription factor peptidase, site-2 protease, antagonizes ABA signaling in Arabidopsis
New Phytol.
208
188-197
2015
Arabidopsis thaliana (F4JUU5)
brenda
Gu, Y.; Lee, W.; Shen, J.
Site-2 protease responds to oxidative stress and regulates oxidative injury in mammalian cells
Sci. Rep.
4
6268
2014
Cricetulus griseus
brenda
Schacherl, M.; Gompert, M.; Pardon, E.; Lamkemeyer, T.; Steyaert, J.; Baumann, U.
Crystallographic and biochemical characterization of the dimeric architecture of site-2 protease
Biochim. Biophys. Acta Biomembr.
1859
1859-1871
2017
Archaeoglobus fulgidus (O29915), Archaeoglobus fulgidus
brenda
Sun, L.; Li, X.; Shi, Y.
Structural biology of intramembrane proteases Mechanistic insights from rhomboid and S2P to gamma-secretase
Curr. Opin. Struct. Biol.
37
97-107
2016
Methanocaldococcus jannaschii (Q57837)
brenda
Yu, Z.; Luo, X.; Wang, C.; Ye, J.; Liu, S.; Xie, L.; Wang, F.; Bao, J.
Baicalin promoted site-2 protease and not site-1 protease in endoplasmic reticulum stress-induced apoptosis of human hepatocellular carcinoma cells
FEBS Open Bio
6
1093-1101
2016
Homo sapiens
brenda
Chen, G.; Li, S.; Liu, X.; Lin, S.; Ding, Q.
Exploration of the involvement of the S2P protease Slr1821 of Synechocystis sp. PCC6803 in heat stress response
Mod. Food Sci. Technol.
33
20-27
2017
Synechocystis sp. PCC 6803 (P73714)
-
brenda
Liu, X.; Chen, G.; Lin, S.; Xu, B.
Importance of the S2P protease Sll0528 of Synechocystis sp. PCC6803 to ammonium stress tolerance
Mod. Food Sci. Technol.
34
29-37
2018
Synechocystis sp. PCC 6803 (Q55518)
-
brenda
Ho, T.D.; Nauta, K.M.; Mueh, U.; Ellermeier, C.D.
Activation of the extracytoplasmic function sigma factor sigmaP by beta-lactams in Bacillus thuringiensis requires the site-2 protease RasP
mSphere
4
e00511-19
2019
Bacillus thuringiensis, Bacillus thuringiensis AW43
brenda
Iwata, Y.; Ashida, M.; Hasegawa, C.; Tabara, K.; Mishiba, K.I.; Koizumi, N.
Activation of the Arabidopsis membrane-bound transcription factor bZIP28 is mediated by site-2 protease, but not site-1 protease
Plant J.
91
408-415
2017
Arabidopsis thaliana
brenda
Koussis, K.; Goulielmaki, E.; Chalari, A.; Withers-Martinez, C.; Siden-Kiamos, I.; Matuschewski, K.; Loukeris, T.G.
Targeted deletion of a Plasmodium site-2 protease impairs life cycle progression in the mammalian host
PLoS ONE
12
e0170260
2017
Plasmodium berghei
brenda
Guan, M.; Su, L.; Yuan, Y.C.; Li, H.; Chow, W.A.
Nelfinavir and nelfinavir analogs block site-2 protease cleavage to inhibit castration-resistant prostate cancer
Sci. Rep.
5
9698
2015
Homo sapiens, Methanocaldococcus jannaschii (Q57837), Methanocaldococcus jannaschii
brenda
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