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any of a group of proteases that mediate apoptosis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/24 17:31:53」(JST)

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Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ^[1] have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family.^[2] Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein.^[3]

Signaling pathway of TNF-R1. Dashed grey lines represent multiple steps

Pathways leading to caspase 3 activation.^[4]

Caspase-3 shares many of the typical characteristics common to all currently-known caspases. For example, its active site contains a cysteine residue (Cys-163) and histidine residue (His-121) that stabilize the peptide bond cleavage of a protein sequence to the carboxy-terminal side of an aspartic acid when it is part of a particular 4-amino acid sequence.^[5]^[6] This specificity allows caspases to be incredibly selective, with a 20,000-fold preference for aspartic acid over glutamic acid.^[7] A key feature of caspases in the cell is that they are present as zymogens, termed procaspases, which are inactive until a biochemical change causes their activation. Each procaspase has an N-terminal large subunit of about 20 kDa followed by a smaller subunit of about 10 kDa, called p20 and p10, respectively.^[8]

Substrate specificity

Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. Caspase 3 and caspase 7 share similar substrate specificity by recognizing tetra-peptide motif Asp-x-x-Asp.^[9] The C-terminal Asp is absolutely required while variations at other three positions can be tolerated.^[10] Caspase substrate specificity has been widely used in caspase based inhibitor and drug design.^[11]

Structure

Caspase-3, in particular, (also known as CPP32/Yama/apopain)^[12]^[13]^[14] is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. When the procaspase is cleaved at a particular residue, the active heterotetramer can then be formed by hydrophobic interactions, causing four anti-parallel beta-sheets from p17 and two from p12 to come together to make a heterodimer, which in turn interacts with another heterodimer to form the full 12-stranded beta-sheet structure surrounded by alpha-helices that is unique to caspases.^[8]^[15] When the heterodimers align head-to-tail with each other, an active site is positioned at each end of the molecule formed by residues from both participating subunits, though the necessary Cys-285 and His-237 residues are found on the p17 (larger) subunit.^[15]

The p12 (pink) and p17 (light blue) subunits of caspase-3 with the beta-sheet structures of each in red and blue, respectively; image generated in Pymol from 1rhm.pdb

Mechanism

The catalytic site of caspase-3 involves the sulfohydryl group of Cys-285 and the imidazole ring of His-237. His-237 stabilizes the carbonyl group of the key aspartate residue, while Cys-285 attacks to ultimately cleave the peptide bond. Cys-285 and Gly-238 also function to stabilize the tetrahedral transition state of the substrate-enzyme complex through hydrogen bonding.^[15] In vitro, caspase-3 has been found to prefer the peptide sequence DEVDG (Asp-Glu-Val-Asp-Gly) with cleavage occurring on the carboxy side of the second aspartic acid residue (between D and G).^[7]^[15]^[16] Caspase-3 is active over a broad pH range that is slightly higher (more basic) than many of the other executioner caspases. This broad range indicates that caspase-3 will be fully active under normal and apoptotic cell conditions.^[17]

Cys-285 (yellow) and His-237 (green and dark blue) in the active site of caspase-3, p12 subunit in pink and p17 subunit in light blue; image generated in Pymol from 1rhr.pdb

Activation

Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways.^[8]^[18] The zymogen feature of caspase-3 is necessary because if unregulated, caspase activity would kill cells indiscriminately.^[19] As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after apoptotic signaling events have occurred.^[20] One such signaling event is the introduction of granzyme B, which can activate initiator caspases, into cells targeted for apoptosis by killer T cells.^[21]^[22] This extrinsic activation then triggers the hallmark caspase cascade characteristic of the apoptotic pathway, in which caspase-3 plays a dominant role.^[6] In intrinsic activation, cytochrome c from the mitochondria works in combination with caspase-9, apoptosis-activating factor 1 (Apaf-1), and ATP to process procaspase-3.^[16]^[22]^[23] These molecules are sufficient to activate caspase-3 in vitro, but other regulatory proteins are necessary in vivo.^[23] Mangosteen (Garcinia Mangostana) extract has been shown to inhibit the activation of caspase 3 in B-amyloid treated human neuronal cells.^[24]

Inhibition

One means of caspase inhibition is through the IAP (inhibitor of apoptosis) protein family, which includes c-IAP1, c-IAP2, XIAP, and ML-IAP.^[15] XIAP binds and inhibits initiator caspase-9, which is directly involved in the activation of executioner caspase-3.^[23] During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, preventing XIAP from being able to bind to inhibit caspase-9 activity.^[25]

Interactions

Caspase 3 has been shown to interact with:

CASP8 ^[26]^[27]
NMT2 ^[28]
CFLAR ^[29]^[30]
DCC ^[31]
GroEL ^[32]^[33]
HCLS1 ^[34]^[35]
Survivin ^[36]^[37]
TRAF3 ^[38]^[39]
XIAP ^[40]^[41]^[42]^[43]^[44]^[45]
NFE2L2 ^[46]

Biological function

Caspase-3 has been found to be necessary for normal brain development as well as its typical role in apoptosis, where it is responsible for chromatin condensation and DNA fragmentation.^[16] Elevated levels of a fragment of Caspase-3, p17, in the bloodstream is a sign of a recent myocardial infarction.^[47] It is now being shown that caspase-3 may play a role in embryonic and hematopoietic stem cell differentiation.^[48]

References

^ "OrthoMaM phylogenetic marker: CASP3 coding sequence".
^ Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW et al. (October 1996). "Human ICE/CED-3 protease nomenclature". Cell 87 (2): 171. doi:10.1016/S0092-8674(00)81334-3. PMID 8861900.
^ "Entrez Gene: CASP3 caspase 3, apoptosis-related cysteine peptidase".
^ Harrington HA, Ho KL, Ghosh S, Tung KC (2008). "Construction and analysis of a modular model of caspase activation in apoptosis". Theor Biol Med Model 5 (1): 26. doi:10.1186/1742-4682-5-26. PMC 2672941. PMID 19077196.
^ Wyllie AH (1997). "Apoptosis: an overview". Br. Med. Bull. 53 (3): 451–65. PMID 9374030.
^ ^a ^b Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Poirier GG et al. (July 1997). "Zinc is a potent inhibitor of the apoptotic protease, caspase-3. A novel target for zinc in the inhibition of apoptosis". J. Biol. Chem. 272 (30): 18530–3. doi:10.1074/jbc.272.30.18530. PMID 9228015.
^ ^a ^b Stennicke HR, Renatus M, Meldal M, Salvesen GS (September 2000). "Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6, 7 and 8". Biochem. J. 350 (2): 563–8. doi:10.1042/0264-6021:3500563. PMC 1221285. PMID 10947972.
^ ^a ^b ^c Salvesen GS (January 2002). "Caspases: opening the boxes and interpreting the arrows". Cell Death Differ. 9 (1): 3–5. doi:10.1038/sj.cdd.4400963. PMID 11803369.
^ Agniswamy J, Fang B, Weber IT (September 2007). "Plasticity of S2-S4 specificity pockets of executioner caspase-7 revealed by structural and kinetic analysis". FEBS J. 274 (18): 4752–65. doi:10.1111/j.1742-4658.2007.05994.x. PMID 17697120.
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^ Weber IT, Fang B, Agniswamy J (October 2008). "Caspases: structure-guided design of drugs to control cell death". Mini Rev Med Chem 8 (11): 1154–62. doi:10.2174/138955708785909899. PMID 18855730.
^ Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1994). "CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme". J. Biol. Chem. 269 (49): 30761–4. PMID 7983002.
^ Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR et al. (June 1995). "Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase". Cell 81 (5): 801–9. doi:10.1016/0092-8674(95)90541-3. PMID 7774019.
^ Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M et al. (July 1995). "Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis". Nature 376 (6535): 37–43. doi:10.1038/376037a0. PMID 7596430.
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^ ^a ^b Katunuma N, Matsui A, Le QT, Utsumi K, Salvesen G, Ohashi A (2001). "Novel procaspase-3 activating cascade mediated by lysoapoptases and its biological significances in apoptosis". Adv. Enzyme Regul. 41 (1): 237–50. doi:10.1016/S0065-2571(00)00018-2. PMID 11384748.
^ ^a ^b ^c Li P, Nijhawan D, Wang X (January 2004). "Mitochondrial activation of apoptosis". Cell 116 (2 Suppl): S57–9, 2 p following S59. doi:10.1016/S0092-8674(04)00031-5. PMID 15055583.
^ Moongkarndi P, Srisawat C, Saetun P, Jantaravinid J, Peerapittayamongkol C, Soi-ampornkul R et al. (May 2010). "Protective effect of mangosteen extract against beta-amyloid-induced cytotoxicity, oxidative stress and altered proteome in SK-N-SH cells". J. Proteome Res. 9 (5): 2076–86. doi:10.1021/pr100049v. PMID 20232907.
^ Denault JB, Eckelman BP, Shin H, Pop C, Salvesen GS (July 2007). "Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9". Biochem. J. 405 (1): 11–9. doi:10.1042/BJ20070288. PMC 1925235. PMID 17437405.
^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.
^ Selvakumar, P.; Sharma, RK. (May 2007). "Role of calpain and caspase system in the regulation of N-myristoyltransferase in human colon cancer (Review).". Int J Mol Med 19 (5): 823–7. doi:10.3892/ijmm.19.5.823. PMID 17390089.
^ Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity 6 (6): 751–63. doi:10.1016/S1074-7613(00)80450-1. PMID 9208847.
^ Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT et al. (October 1997). "MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11333–8. doi:10.1073/pnas.94.21.11333. PMC 23459. PMID 9326610.
^ Forcet C, Ye X, Granger L, Corset V, Shin H, Bredesen DE et al. (March 2001). "The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3416–21. doi:10.1073/pnas.051378298. PMC 30668. PMID 11248093.
^ Samali A, Cai J, Zhivotovsky B, Jones DP, Orrenius S (April 1999). "Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells". EMBO J. 18 (8): 2040–8. doi:10.1093/emboj/18.8.2040. PMC 1171288. PMID 10205158.
^ Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R et al. (April 1999). "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. 18 (8): 2049–56. doi:10.1093/emboj/18.8.2049. PMC 1171289. PMID 10205159.
^ Ruzzene M, Penzo D, Pinna LA (May 2002). "Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells". Biochem. J. 364 (Pt 1): 41–7. PMC 1222543. PMID 11988074.
^ Chen YR, Kori R, John B, Tan TH (November 2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis". Biochem. Biophys. Res. Commun. 288 (4): 981–9. doi:10.1006/bbrc.2001.5862. PMID 11689006.
^ Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T et al. (December 1998). "IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs". Cancer Res. 58 (23): 5315–20. PMID 9850056.
^ Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI et al. (January 2001). "An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7". Biochemistry 40 (4): 1117–23. doi:10.1021/bi001603q. PMID 11170436.
^ Lee ZH, Lee SE, Kwack K, Yeo W, Lee TH, Bae SS et al. (March 2001). "Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells". J. Leukoc. Biol. 69 (3): 490–6. PMID 11261798.
^ Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR et al. (March 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 (11): 8087–93. doi:10.1074/jbc.M009450200. PMID 11098060.
^ Suzuki Y, Nakabayashi Y, Takahashi R (July 2001). "Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8662–7. doi:10.1073/pnas.161506698. PMC 37492. PMID 11447297.
^ Silke J, Hawkins CJ, Ekert PG, Chew J, Day CL, Pakusch M et al. (April 2002). "The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites". J. Cell Biol. 157 (1): 115–24. doi:10.1083/jcb.200108085. PMC 2173256. PMID 11927604.
^ Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW et al. (March 2001). "Structural basis for the inhibition of caspase-3 by XIAP". Cell 104 (5): 791–800. doi:10.1016/S0092-8674(01)00274-4. PMID 11257232.
^ Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (December 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. 16 (23): 6914–25. doi:10.1093/emboj/16.23.6914. PMC 1170295. PMID 9384571.
^ Deveraux QL, Takahashi R, Salvesen GS, Reed JC (July 1997). "X-linked IAP is a direct inhibitor of cell-death proteases". Nature 388 (6639): 300–4. doi:10.1038/40901. PMID 9230442.
^ Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R (July 2001). "X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes". J. Biol. Chem. 276 (29): 27058–63. doi:10.1074/jbc.M102415200. PMID 11359776.
^ Ohtsubo T, Kamada S, Mikami T, Murakami H, Tsujimoto Y (1999). "Identification of NRF2, a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases.". Cell Death Differ. 6 (9): 865–872. doi:10.1038/sj.cdd.4400566. PMID 10510468.
^ Agosto M, Azrin M, Singh K, Jaffe AS, Liang BT (January 2011). "Serum caspase-3 p17 fragment is elevated in patients with ST-segment elevation myocardial infarction: a novel observation". J. Am. Coll. Cardiol. 57 (2): 220–1. doi:10.1016/j.jacc.2010.08.628. PMID 21211695.
^ Abdul-Ghani M, Megeney LA (June 2008). "Rehabilitation of a contract killer: caspase-3 directs stem cell differentiation". Cell Stem Cell 2 (6): 515–6. doi:10.1016/j.stem.2008.05.013. PMID 18522841.

External links

The MEROPS online database for peptidases and their inhibitors: C14.003
Media related to caspase 3 at Wikimedia Commons
Apoptosis & Caspase 3 - The Proteolysis Map-animation

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Oxidative stress-mediated antiproliferative effects of furan-containing sulfur flavors in human leukemia Jurkat cells.

Zhang GL1, Liang Y1, Zhu JY1, Jia Q1, Gan WQ1, Sun LM1, Hou HM2.
Food chemistry.Food Chem.2015 Aug 1;180:1-8. doi: 10.1016/j.foodchem.2015.01.122. Epub 2015 Jan 31.
Antiproliferative effects of 15 sulfides were investigated in human leukemia Jurkat cells. Treatment with 5-50μM of nine monosulfides and two linear disulfides did not induce DNA fragmentation. Whereas, furan-containing sulfur flavors including methyl 2-methyl-3-furyl disulfide (MMFDS), bis (2-meth
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Inhibition of Forkhead box protein M1 by thiostrepton increases chemosensitivity to doxorubicin in T-cell acute lymphoblastic leukemia.

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood malignancy, deriving from T-cell progenitors in the thymus, and comprises 10‑15% of pediatric and 25% of adult primary ALL cases. Despite advances, 20% of pediatric and the majority of adult patients with T-ALL succumb to
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PMID 25684548

Japanese Journal

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

, , [他],
The Journal of Toxicological Sciences 40(1), 115-126, 2015
… The K562 cells were treated with various concentrations of the spiroquinazolinone (10-300 µM) for 3 days and cell viability was determined by MTT growth inhibition assay. … 4t-QTC was more active among these compounds with IC50 of 50 ± 3.6 µM and was selected for further studies. … The K562 cells underwent apoptosis upon a single dose (at IC50 value) of the 4t-QTC compound, and over-expressed caspase-3 expression by more than 1.7-fold, following a 72 hr treatment. …
NAID 130004904026

Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

, , [他],
The Journal of Toxicological Sciences 40(1), 71-76, 2015
… Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 μg/mL). … Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladenine, an inhibitor of autophagosome formation. …
NAID 130004904025

Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl2/Bax pathway

, , , , , , ,
Journal of Occupational Health advpub(0), 2015
… Groups 2-4 were given arsenic trioxide (As2O3) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. … The activity of caspase-3 was determined by spectrophotometry. … Moreover, the activity of caspase-3 in the hippocampus of mice exposed to As was higher than that in the control (p<0.05). …
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「カスパーゼ」

Caspase 3, apoptosis-related cysteine peptidase
	PDB rendering based on 1rhk.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1CP3, 1GFW, 1I3O, 1NME, 1NMQ, 1NMS, 1PAU, 1QX3, 1RE1, 1RHJ, 1RHK, 1RHM, 1RHQ, 1RHR, 1RHU, 2C1E, 2C2K, 2C2M, 2C2O, 2CDR, 2CJX, 2CJY, 2CNK, 2CNL, 2CNN, 2CNO, 2DKO, 2H5I, 2H5J, 2H65, 2J30, 2J31, 2J32, 2J33, 2XYG, 2XYH, 2XYP, 2XZD, 2XZT, 2Y0B, 3DEH, 3DEI, 3DEJ, 3DEK, 3EDQ, 3GJQ, 3GJR, 3GJS, 3GJT, 3H0E, 3ITN, 3KJF, 3PCX, 3PD0, 3PD1, 4DCJ, 4DCO, 4DCP, 4EHA, 4EHD, 4EHF, 4EHH, 4EHK, 4EHL, 4EHN, 4JJE, 4JQY, 4JQZ, 4JR0, 4PRY, 4PS0, 4QTX, 4QTY, 4QU0, 4QU5, 4QU8, 4QU9, 4QUA, 4QUB, 4QUD, 4QUE, 4QUG, 4QUH, 4QUI, 4QUJ, 4QUL
Identifiers
Symbols	CASP3 ; CPP32; CPP32B; SCA-1
External IDs	OMIM: 600636 MGI: 107739 HomoloGene: 37912 ChEMBL: 2334 GeneCards: CASP3 Gene
EC number	3.4.22.56
Gene ontology
Molecular function	• protease binding; • aspartic-type endopeptidase activity; • cysteine-type endopeptidase activity; • cyclin-dependent protein serine/threonine kinase inhibitor activity; • death receptor binding; • protein binding; • peptidase activity; • phospholipase A2 activator activity; • protein complex binding; • cysteine-type endopeptidase activity involved in apoptotic process; • cysteine-type endopeptidase activity involved in execution phase of apoptosis;
Cellular component	• nucleus; • nucleoplasm; • cytoplasm; • cytosol; • plasma membrane; • death-inducing signaling complex; • membrane raft;
Biological process	• response to hypoxia; • B cell homeostasis; • apoptotic DNA fragmentation; • proteolysis; • apoptotic process; • cellular component disassembly involved in execution phase of apoptosis; • cellular response to DNA damage stimulus; • heart development; • sensory perception of sound; • learning or memory; • activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; • response to UV; • response to glucose; • response to X-ray; • programmed cell death; • hippocampus development; • extracellular matrix disassembly; • neuron differentiation; • extracellular matrix organization; • keratinocyte differentiation; • erythrocyte differentiation; • platelet formation; • negative regulation of B cell proliferation; • response to cobalt ion; • response to estradiol; • response to lipopolysaccharide; • glial cell apoptotic process; • response to tumor necrosis factor; • response to nicotine; • hippo signaling; • wound healing; • response to drug; • response to hydrogen peroxide; • T cell homeostasis; • negative regulation of apoptotic process; • response to amino acid; • regulation of cysteine-type endopeptidase activity involved in apoptotic process; • positive regulation of neuron apoptotic process; • cell fate commitment; • negative regulation of cyclin-dependent protein serine/threonine kinase activity; • negative regulation of activated T cell proliferation; • response to antibiotic; • neurotrophin TRK receptor signaling pathway; • response to glucocorticoid; • cellular response to organic cyclic compound; • apoptotic signaling pathway; • extrinsic apoptotic signaling pathway; • extrinsic apoptotic signaling pathway in absence of ligand; • intrinsic apoptotic signaling pathway; • execution phase of apoptosis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: caspase
同: ICEファミリープロテアーゼ ICE family protease

ヒトICEプロテアーゼスーパーファミリー

Family	Caspase	Other Name	Recognition	Target (Truncation site)
caspase-1	caspase-1	ICE	WEHD	pro IL-1β (FEAD/G, YVHD/A), procaspase-3, procaspase-4
	caspase-4	ICErel-II, TX, ICH-2
	caspase-5	ICErel-III, TY
caspase-2	caspase-2	ICH-1	DEHD	PARP (DEVD/G)
caspase-2	caspase-9	ICE-LAP6, Mch6	LEHD	PARP, procaspase-3
caspase-3	caspase-3	CPP32, Yama	DEVD	PARP, SREBP (DEPD/S), U1snRNP (DGPD/G), lamin B, D4-GDI (DELD/S), DNA-PK (DEVD/N), DFF (DETD/S, DAVD/T), actin (ELPD/G) ?, PKCδ (DMQD/N) ?]]
	caspase-7	Mch3, ICE-LAP3, CMH-1	DEVD	PARP, procaspase-6
	caspase-6	Mch2	VEHD	lamin A (VEID/N)]]
	caspase-8	FLICE, MACH, Mch5	LETD	procaspase-3, Bid
	caspase-10	Mch4	LEXD
	caspase-11	Ich3

[OrthoMaM-1] "OrthoMaM phylogenetic marker: CASP3 coding sequence".

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案内

caspase-3