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Information on EC 3.4.22.58 - caspase-5 and Organism(s) Homo sapiens and UniProt Accession P51878
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3.4.22.58 caspase-5Specify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp-/- but also cleaves at Asp-Glu-Val-Asp-/-
Synonyms
caspase-5, cas-5, caspase 5, ty protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C14.008
-
-
-
-
caspase 5
-
-
-
-
ICE(rel)-III
-
-
-
-
ICErelIII/TY
-
-
-
-
ICH-3 protease
-
-
-
-
transcript Y
-
-
-
-
TY
-
-
-
-
TY protease
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
192465-11-5
-
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
pro-caspase-5 + H2O
?
caspase-5 has protease activity on its own precursor
-
-
?
acetyl-WEHD-7-amido-4-methylcoumarin + H2O
acetyl-WEHD + 7-amino-4-methylcoumarin
-
optimal tetrapeptide recognition motif
-
-
?
interleukin-1beta + H2O
?
-
50 nM enzyme partly cleaves interleukin-1beta into the 28000 Da form and a very faint 17500 Da band can be detected, with other dilutions of TY no cleavage is detected
-
-
?
MDIGAYPHFMPTNLAGDPY + H2O
AYPHFMPTNLA + AYPHFMPTNLAGD + DIGAYPHFMPTNLAG + IGAYPHFMPTNLAGD + MDIGAYPHFMPTNL + MDIGAYPHFMPTNLA + MDIGAYPHFMPTNLAGD + MDIGAYPHFMPTNLAGDP + Met + MDIG + Met-Asp + Tyr + Pro-Tyr + GDPY + DPY
-
-
quantitative product mass spectrometric analysis, overview
-
?
succinyl-YVAD-7-amido-4-methylcoumarin + H2O
succinyl-YVAD + 7-amino-4-methylcoumarin
-
-
-
-
?
additional information
?
-
the enzyme fails to process the interleukin-1beta precursor, activity is dependent on the presence of a cysteine residue at position 245
-
-
?
additional information
?
-
the enzyme is able to induce apoptosis when overexpressed in COS cells
-
-
?
additional information
?
-
-
very little efficiency on caspase-1 substrates
-
-
?
additional information
?
-
-
the enzyme cleaves the substrates in the order of increasing efficiency: p35, pro-caspase-3, CrmA
-
-
?
additional information
?
-
-
the preferred cleavage sequence is WEHD-/- or LEHD-/-
-
-
?
additional information
?
-
-
the preferred cleavage sequence is WEHD-/- or LEHD-/-
-
-
?
additional information
?
-
-
the enzyme is involved in cytokine activation
-
-
?
additional information
?
-
-
the production of the enzyme induces the activation of an endogenous 32000 Da putative cysteine protease (CPP32) like caspase
-
-
?
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
additional information
?
-
the enzyme is able to induce apoptosis when overexpressed in COS cells
-
-
?
additional information
?
-
-
the enzyme is involved in cytokine activation
-
-
?
additional information
?
-
-
the production of the enzyme induces the activation of an endogenous 32000 Da putative cysteine protease (CPP32) like caspase
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
dexamethasone, interleukin-10, and triamcinolone acetonide block activation of caspase-5. Activation of caspase-5 is also inhibited by caspase-1-specific inhibitor Z-YVAD-FMK
-
additional information
-
identification of specific tethered inhibitors for caspase-5, screening, overview. A naphthyl-thiazole-containing molecule selectively inhibits and labels the allosteric cysteine in the p10 subunit of caspase-5, but causes very little inhibition or labeling of caspase-1. Some of allosteric tethered compounds to caspase-5 do not inhibit its enzymatic activity, suggesting that thiol-labeling itself is not sufficient to drive inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
activation of caspase-5 is enhanced by ATP and endoplasmic reticulum stress inducers, and 2.2-5.4fold by interleukin-1beta, TNF-alpha, lipopolysaccharide and hRPE cell co-culture, but not by IFN-gamma
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the Ki-value for cowpox serpin CrmA is below below 0.1 nM
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary cultured hRPE cells, telomerase-immortalized hTERT-RPE1 cells
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
-
caspase-5 knockdown by shRNA reduces caspase-1 protein expression and activation and inhibited TNF-alphainduced interleukin-8 and MCP-1
physiological function
physiological function
caspase-4 and caspase-5 are the key determinants of one-step inflammasome activation in human monocyte. The contribute to TLR4-mediated IL-1alpha/beta release from human monocytes
physiological function
caspase-5 rescues UVB-dependent IL-1beta activity in apoptosis-associated speck-like protein containing a CARD (ASC)-deficient epidermal keratinocyte
physiological function
membrane vesicles from Pseudomonas aeruginosa activate the noncanonical inflammasome in human monocytes through caspase-5
physiological function
-
caspase-5 is an initiator caspase of proinflammatory and apoptotic pathways induced by vaccinia infection. The processing of a short vaccinia virus-encoded antigen can take place by a proteasome-independent pathway involving initiator caspase-5 and -10, which generate antigenic peptides recognized by CD8+ T lymphocytes. Each enzyme can use the degradation products of the other as substrate for new cleavages, indicating concerted endoproteolytic activity of caspase-5 and -10, EC 3.4.22.58 and EC 3.4.22.63
physiological function
-
functional roles of caspase-5 in inflammatory responses of human retinal pigment epithelial cells. Involvement of caspase-5 in tunicamycin-induced apoptotic cell death, similar to caspase-4, EC 3.4.22.57
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). CASP5_HUMAN
434
0
49736
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
synthesized as a larger proenzyme which is proteolytically processed to form a heterodimeric active enzyme
proteolytic modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
the enzyme is expressed in baculovirus-infected insect cells, as a 30000 Da protein lacking the propeptide
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
caspase-5 is induced 1.9-2.3fold by interleukin-1beta, TNF-alpha, lipopolysaccharide and hRPE cell co-culture, but not by IFN-gamma
-
expression of caspase-5 is inhibited by caspase-1-specific inhibitor Z-YVAD-fluoromethylketone
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Garcia-Calvo, M.; Peterson, E.P.; Leiting, B.; Ruel, R.; Nicholson, D.W.; Thornberry, N.A.
Inhibition of human caspases by peptide-based and macromolecular inhibitors
J. Biol. Chem.
273
32608-32613
1998
Homo sapiens
Garcia-Calvo, M.; Peterson, E.P.; Rasper, D.M.; Vaillancourt, J.P.; Zamboni, R.; Nicholson, D.W.; Thornberry, N.A.
Purification and catalytic properties of human caspase family members
Cell Death Differ.
6
362-369
1999
Homo sapiens
Chang, H.Y.; Yang, X.
Proteases from cell suicide: functions and regulation of caspases
Microbiol. Mol. Biol. Rev.
64
821-846
2000
Homo sapiens
Thornberry, N.A.; Rano, T.A.; Peterson, E.P.; et al.
A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis
J. Biol. Chem.
272
17907-17911
1997
Homo sapiens
Faucheu, C.; Blanchet, A.M.; Collard-Dutilleul, V.; Lalanne, J.L.; Diu-Hercend, A.
Identification of a cysteine protease closely related to interleukin-1 beta-converting enzyme
Eur. J. Biochem.
236
207-213
1996
Homo sapiens (P51878)
Munday N.A.; Vaillancourt J.P.; Ali A.; Casano F.J.; Miller D.K.; Molineaux S.M.; Yamin T.T.; Yu V.L.; Nicholson D.W.
Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases
J. Biol. Chem.
270
15870-15876
1995
Homo sapiens (P51878)
Kamada, S.; Funahashi, Y.; Tsujimoto, Y.
Caspase-4 and caspase-5, members of the ICE/CED-3 family of cysteine proteases, are CrmA-inhibitable proteases
Cell Death Differ.
4
473-478
1997
Homo sapiens
Fassy, F.; Krebs, O.; Rey, H.; Komara, B.; Gillard, C.; Capdevila, C.; Yea, C.; Faucheu, C.; Blanchet, A.M.; Miossec, C.; Diu-Hercend, A.
Enzymic activity of two caspases related to interleukin-1beta-converting enzyme
Eur. J. Biochem.
253
76-83
1998
Homo sapiens
Eckhart, L.; Kittel, C.; Gawlas, S.; Gruber, F.; Mildner, M.; Jilma, B.; Tschachler, E.
Identification of a novel exon encoding the amino-terminus of the predominant caspase-5 variants
Biochem. Biophys. Res. Commun.
348
682-688
2006
Homo sapiens (P51878), Homo sapiens
Trojan, J.; Brieger, A.; Raedle, J.; Weber, N.; Kriener, S.; Kronenberger, B.; Caspary, W.F.; Zeuzem, S.
BAX and caspase-5 frameshift mutations and spontaneous apoptosis in colorectal cancer with microsatellite instability
Int. J. Colorectal Dis.
19
538-544
2004
Homo sapiens
Offman, J.; Gascoigne, K.; Bristow, F.; Macpherson, P.; Bignami, M.; Casorelli, I.; Leone, G.; Pagano, L.; Sica, S.; Halil, O.; Cummins, D.; Banner, N.R.; Karran, P.
Repeated sequences in CASPASE-5 and FANCD2 but not NF1 are targets for mutation in microsatellite-unstable acute leukemia/myelodysplastic syndrome
Mol. Cancer Res.
3
251-260
2005
Homo sapiens
Gao, J.; Wells, J.A.
Identification of specific tethered inhibitors for caspase-5
Chem. Biol. Drug Des.
79
209-215
2012
Homo sapiens
Bian, Z.M.; Elner, S.G.; Khanna, H.; Murga-Zamalloa, C.A.; Patil, S.; Elner, V.M.
Expression and functional roles of caspase-5 in inflammatory responses of human retinal pigment epithelial cells
Invest. Ophthalmol. Vis. Sci.
52
8646-8656
2011
Homo sapiens
Lopez, D.; Jimenez, M.; Garcia-Calvo, M.; Del Val, M.
Concerted antigen processing of a short viral antigen by human caspase-5 and -10
J. Biol. Chem.
286
16910-16913
2011
Homo sapiens
Bitto, N.J.; Baker, P.J.; Dowling, J.K.; Wray-McCann, G.; De Paoli, A.; Tran, L.S.; Leung, P.L.; Stacey, K.J.; Mansell, A.; Masters, S.L.; Ferrero, R.L.
Membrane vesicles from Pseudomonas aeruginosa activate the noncanonical inflammasome through caspase-5 in human monocytes
Immunol. Cell Biol.
96
1120-1130
2018
Homo sapiens (P51878), Homo sapiens
Vigano, E.; Diamond, C.E.; Spreafico, R.; Balachander, A.; Sobota, R.M.; Mortellaro, A.
Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes
Nat. Commun.
6
8761
2015
Homo sapiens (P51878), Homo sapiens
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