ID CASP3_HUMAN Reviewed; 277 AA. AC P42574; A8K5M2; D3DP53; Q96AN1; Q96KP2; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 2. DT 27-MAR-2024, entry version 247. DE RecName: Full=Caspase-3 {ECO:0000303|PubMed:15003516, ECO:0000303|PubMed:18723680}; DE Short=CASP-3; DE EC=3.4.22.56 {ECO:0000269|PubMed:23152800, ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:30878284, ECO:0000269|PubMed:33725486, ECO:0000269|PubMed:7596430}; DE AltName: Full=Apopain {ECO:0000303|PubMed:8696339}; DE AltName: Full=Cysteine protease CPP32 {ECO:0000303|PubMed:7774019}; DE Short=CPP-32 {ECO:0000303|PubMed:7774019, ECO:0000303|PubMed:9334240}; DE AltName: Full=Protein Yama {ECO:0000303|PubMed:7774019}; DE AltName: Full=SREBP cleavage activity 1; DE Short=SCA-1; DE Contains: DE RecName: Full=Caspase-3 subunit p17; DE Contains: DE RecName: Full=Caspase-3 subunit p12; DE Flags: Precursor; GN Name=CASP3; Synonyms=CPP32 {ECO:0000303|PubMed:7983002}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-190, AND TISSUE SPECIFICITY. RC TISSUE=T-cell; RX PubMed=7983002; DOI=10.1016/s0021-9258(18)47344-9; RA Fernandes-Alnemri T., Litwack G., Alnemri E.S.; RT "CPP32, a novel human apoptotic protein with homology to Caenorhabditis RT elegans cell death protein Ced-3 and mammalian interleukin-1 beta- RT converting enzyme."; RL J. Biol. Chem. 269:30761-30764(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=7774019; DOI=10.1016/0092-8674(95)90541-3; RA Tewari M., Quan L.T., O'Rourke K., Desnoyers S., Zeng Z., Beidler D.R., RA Poirier G.G., Salvesen G.S., Dixit V.M.; RT "Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable RT protease that cleaves the death substrate poly(ADP-ribose) polymerase."; RL Cell 81:801-809(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND VARIANT ASP-190. RX PubMed=15003516; DOI=10.1016/j.bbrc.2004.02.021; RA Pelletier M., Cartron P.F., Delaval F., Meflah K., Vallette F.M., RA Oliver L.; RT "Caspase 3 activation is controlled by a sequence located in the N-terminus RT of its large subunit."; RL Biochem. Biophys. Res. Commun. 316:93-99(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 29-46 AND 176-193, FUNCTION, CATALYTIC ACTIVITY, AND RP VARIANT ASP-190. RX PubMed=7596430; DOI=10.1038/376037a0; RA Nicholson D.W., Ali A., Thornberry N.A., Vaillancourt J.P., Ding C.K., RA Gallant M., Gareau Y., Griffin P.R., Labelle M., Lazebnik Y.A., RA Munday N.A., Raju S.M., Smulson M.E., Yamin T.-T., Li V.L., Miller D.K.; RT "Identification and inhibition of the ICE/CED-3 protease necessary for RT mammalian apoptosis."; RL Nature 376:37-43(1995). RN [9] RP PROTEOLYTIC PROCESSING. RX PubMed=8755496; DOI=10.1073/pnas.93.15.7464; RA Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M., RA Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G., RA Alnemri E.S.; RT "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic RT cysteine protease containing two FADD-like domains."; RL Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996). RN [10] RP CLEAVAGE OF HUNTINGTIN, AND FUNCTION. RX PubMed=8696339; DOI=10.1038/ng0896-442; RA Goldberg Y.P., Nicholson D.W., Rasper D.M., Kalchman M.A., Koide H.B., RA Graham R.K., Bromm M., Kazemi-Esfarjani P., Thornberry N.A., RA Vaillancourt J.P., Hayden M.R.; RT "Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is RT modulated by the polyglutamine tract."; RL Nat. Genet. 13:442-449(1996). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9334240; DOI=10.1074/jbc.272.42.26595; RA Akita K., Ohtsuki T., Nukada Y., Tanimoto T., Namba M., Okura T., RA Takakura-Yamamoto R., Torigoe K., Gu Y., Su M.S., Fujii M., Satoh-Itoh M., RA Yamamoto K., Kohno K., Ikeda M., Kurimoto M.; RT "Involvement of caspase-1 and caspase-3 in the production and processing of RT mature human interleukin 18 in monocytic THP.1 cells."; RL J. Biol. Chem. 272:26595-26603(1997). RN [12] RP FUNCTION. RX PubMed=10497198; DOI=10.1074/jbc.274.40.28379; RA Germain M., Affar E.B., D'Amours D., Dixit V.M., Salvesen G.S., RA Poirier G.G.; RT "Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. RT Evidence for involvement of caspase-7."; RL J. Biol. Chem. 274:28379-28384(1999). RN [13] RP S-NITROSYLATION AT CYS-163. RX PubMed=10213689; DOI=10.1126/science.284.5414.651; RA Mannick J.B., Hausladen A., Liu L., Hess D.T., Zeng M., Miao Q.X., RA Kane L.S., Gow A.J., Stamler J.S.; RT "Fas-induced caspase denitrosylation."; RL Science 284:651-654(1999). RN [14] RP INTERACTION WITH BIRC6/BRUCE. RX PubMed=15200957; DOI=10.1016/j.molcel.2004.05.018; RA Bartke T., Pohl C., Pyrowolakis G., Jentsch S.; RT "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin RT ligase."; RL Mol. Cell 14:801-811(2004). RN [15] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=16374543; DOI=10.1007/s10495-005-3276-y; RA Rodriguez-Hernandez A., Brea-Calvo G., Fernandez-Ayala D.J., Cordero M., RA Navas P., Sanchez-Alcazar J.A.; RT "Nuclear caspase-3 and caspase-7 activation, and poly(ADP-ribose) RT polymerase cleavage are early events in camptothecin-induced apoptosis."; RL Apoptosis 11:131-139(2006). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=18723680; DOI=10.1073/pnas.0707715105; RA Walsh J.G., Cullen S.P., Sheridan C., Luethi A.U., Gerner C., Martin S.J.; RT "Executioner caspase-3 and caspase-7 are functionally distinct proteases."; RL Proc. Natl. Acad. Sci. U.S.A. 105:12815-12819(2008). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=20566630; DOI=10.1074/jbc.m110.126573; RA Nakatsumi H., Yonehara S.; RT "Identification of functional regions defining different activity in RT caspase-3 and caspase-7 within cells."; RL J. Biol. Chem. 285:25418-25425(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP FUNCTION IN CELL ADHESION. RX PubMed=21357690; DOI=10.1074/jbc.m110.195461; RA Cabrera J.R., Bouzas-Rodriguez J., Tauszig-Delamasure S., Mehlen P.; RT "RET modulates cell adhesion via its cleavage by caspase in sympathetic RT neurons."; RL J. Biol. Chem. 286:14628-14638(2011). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [22] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23152800; DOI=10.1371/journal.pone.0048770; RA Sen T., Sen N., Noordhuis M.G., Ravi R., Wu T.C., Ha P.K., Sidransky D., RA Hoque M.O.; RT "OGDHL is a modifier of AKT-dependent signaling and NF-kappaB function."; RL PLoS ONE 7:e48770-e48770(2012). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23845944; DOI=10.1126/science.1236758; RA Suzuki J., Denning D.P., Imanishi E., Horvitz H.R., Nagata S.; RT "Xk-Related protein 8 and CED-8 promote phosphatidylserine exposure in RT apoptotic cells."; RL Science 341:403-406(2013). RN [25] RP FUNCTION. RX PubMed=28459430; DOI=10.1038/nature22393; RA Wang Y., Gao W., Shi X., Ding J., Liu W., He H., Wang K., Shao F.; RT "Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a RT gasdermin."; RL Nature 547:99-103(2017). RN [26] RP FUNCTION. RX PubMed=28045099; DOI=10.1038/ncomms14128; RA Rogers C., Fernandes-Alnemri T., Mayes L., Alnemri D., Cingolani G., RA Alnemri E.S.; RT "Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to RT secondary necrotic/pyroptotic cell death."; RL Nat. Commun. 8:14128-14128(2017). RN [27] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30878284; DOI=10.1016/j.molcel.2019.02.013; RA Ning X., Wang Y., Jing M., Sha M., Lv M., Gao P., Zhang R., Huang X., RA Feng J.M., Jiang Z.; RT "Apoptotic caspases suppress type i interferon production via the cleavage RT of cGAS, MAVS, and IRF3."; RL Mol. Cell 74:19-31(2019). RN [28] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33725486; DOI=10.1016/j.molcel.2021.02.025; RA Maruoka M., Zhang P., Mori H., Imanishi E., Packwood D.M., Harada H., RA Kosako H., Suzuki J.; RT "Caspase cleavage releases a nuclear protein fragment that stimulates RT phospholipid scrambling at the plasma membrane."; RL Mol. Cell 81:1397-1410(2021). RN [29] RP FUNCTION, PROTEOLYTIC CLEAVAGE, ADP-RIBOXANATION AT ARG-207 (MICROBIAL RP INFECTION), AND MUTAGENESIS OF ARG-207. RX PubMed=35446120; DOI=10.1128/mbio.00690-22; RA Liu Y., Zeng H., Hou Y., Li Z., Li L., Song X., Ding J., Shao F., Xu Y.; RT "Calmodulin binding activates chromobacterium CopC effector to ADP- RT riboxanate host apoptotic caspases."; RL MBio 0:0-0(2022). RN [30] RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND ADP-RIBOXANATION AT ARG-207 (MICROBIAL RP INFECTION). RX PubMed=35338844; DOI=10.1016/j.molcel.2022.03.010; RA Peng T., Tao X., Xia Z., Hu S., Xue J., Zhu Q., Pan X., Zhang Q., Li S.; RT "Pathogen hijacks programmed cell death signaling by arginine ADPR- RT deacylization of caspases."; RL Mol. Cell 82:1806-1820(2022). RN [31] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=37993714; DOI=10.1038/s41586-023-06742-w; RA Shi X., Sun Q., Hou Y., Zeng H., Cao Y., Dong M., Ding J., Shao F.; RT "Recognition and maturation of IL-18 by caspase-4 noncanonical RT inflammasome."; RL Nature 0:0-0(2023). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 28-277. RX PubMed=8673606; DOI=10.1038/nsb0796-619; RA Rotonda J., Nicholson D.W., Fazil K.M., Gallant M., Gareau Y., Labelle M., RA Peterson E.P., Rasper D.M., Ruel R., Vaillancourt J.P., Thornberry N.A., RA Becker J.W.; RT "The three-dimensional structure of apopain/CPP32, a key mediator of RT apoptosis."; RL Nat. Struct. Biol. 3:619-625(1996). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 35-173 AND 185-277. RX PubMed=9045680; DOI=10.1074/jbc.272.10.6539; RA Mittl P.R.E., di Marco S., Krebs J.F., Bai X., Karanewsky D.S., RA Priestle J.P., Tomaselli K.J., Gruetter M.G.; RT "Structure of recombinant human CPP32 in complex with the tetrapeptide RT acetyl-Asp-Val-Ala-Asp fluoromethyl ketone."; RL J. Biol. Chem. 272:6539-6547(1997). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=10821855; DOI=10.1074/jbc.275.21.16007; RA Lee D., Long S.A., Adams J.L., Chan G., Vaidya K.S., Francis T.A., RA Kikly K., Winkler J.D., Sung C.-M., Debouck C., Richardson S., Levy M.A., RA DeWolf W.E. Jr., Keller P.M., Tomaszek T., Head M.S., Ryan M.D., RA Haltiwanger R.C., Liang P.-H., Janson C.A., McDevitt P.J., Johanson K., RA Concha N.O., Chan W., Abdel-Meguid S.S., Badger A.M., Lark M.W., RA Nadeau D.P., Suva L.J., Gowen M., Nuttall M.E.; RT "Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit RT apoptosis and maintain cell functionality."; RL J. Biol. Chem. 275:16007-16014(2000). RN [35] {ECO:0007744|PDB:4JQY, ECO:0007744|PDB:4JQZ, ECO:0007744|PDB:4JR0} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 34-277 IN COMPLEX WITH COVALENT RP INHIBITORS, AND MUTAGENESIS OF ASP-9; ASP-28 AND ASP-175. RX PubMed=23650375; DOI=10.1073/pnas.1306759110; RA Thomsen N.D., Koerber J.T., Wells J.A.; RT "Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 RT activation."; RL Proc. Natl. Acad. Sci. U.S.A. 110:8477-8482(2013). RN [36] RP STRUCTURE BY ELECTRON MICROSCOPY (3.18 ANGSTROMS) IN COMPLEX WITH RP C.VIOLACEUM COPC AND CALMODULIN, ADP-RIBOXANATION AT ARG-207 (MICROBIAL RP INFECTION), AND MUTAGENESIS OF ARG-207. RX PubMed=36423631; DOI=10.1016/j.molcel.2022.10.032; RA Zhang K., Peng T., Tao X., Tian M., Li Y., Wang Z., Ma S., Hu S., Pan X., RA Xue J., Luo J., Wu Q., Fu Y., Li S.; RT "Structural insights into caspase ADPR deacylization catalyzed by a RT bacterial effector and host calmodulin."; RL Mol. Cell 0:0-0(2022). CC -!- FUNCTION: Thiol protease that acts as a major effector caspase involved CC in the execution phase of apoptosis (PubMed:7596430, PubMed:18723680, CC PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120). CC Following cleavage and activation by initiator caspases (CASP8, CASP9 CC and/or CASP10), mediates execution of apoptosis by catalyzing cleavage CC of many proteins (PubMed:7596430, PubMed:18723680, PubMed:20566630, CC PubMed:23650375). At the onset of apoptosis, it proteolytically cleaves CC poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond CC (PubMed:7774019, PubMed:7596430, PubMed:10497198, PubMed:16374543). CC Cleaves and activates sterol regulatory element binding proteins CC (SREBPs) between the basic helix-loop-helix leucine zipper domain and CC the membrane attachment domain (By similarity). Cleaves and activates CC caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) CC (PubMed:7596430). Cleaves and inactivates interleukin-18 (IL18) CC (PubMed:9334240, PubMed:37993714). Involved in the cleavage of CC huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic CC neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits CC serine/threonine-protein kinase AKT1 in response to oxidative stress CC (PubMed:23152800). Acts as an inhibitor of type I interferon production CC during virus-induced apoptosis by mediating cleavage of antiviral CC proteins CGAS, IRF3 and MAVS, thereby preventing cytokine CC overproduction (PubMed:30878284). Also involved in pyroptosis by CC mediating cleavage and activation of gasdermin-E (GSDME) CC (PubMed:35446120, PubMed:35338844). Cleaves XRCC4 and phospholipid CC scramblase proteins XKR4, XKR8 and XKR9, leading to promote CC phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, CC PubMed:33725486). {ECO:0000250|UniProtKB:Q60431, CC ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:16374543, CC ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:20566630, CC ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:23152800, CC ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23845944, CC ECO:0000269|PubMed:30878284, ECO:0000269|PubMed:33725486, CC ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, CC ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7596430, CC ECO:0000269|PubMed:7774019, ECO:0000269|PubMed:8696339, CC ECO:0000269|PubMed:9334240}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Strict requirement for an Asp residue at positions P1 and P4. CC It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a CC hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid CC residue at P3, although Val or Ala are also accepted at this CC position.; EC=3.4.22.56; Evidence={ECO:0000269|PubMed:16374543, CC ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:20566630, CC ECO:0000269|PubMed:23152800, ECO:0000269|PubMed:23650375, CC ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:30878284, CC ECO:0000269|PubMed:33725486, ECO:0000269|PubMed:37993714, CC ECO:0000269|PubMed:7596430, ECO:0000269|PubMed:9334240}; CC -!- ACTIVITY REGULATION: Inhibited by isatin sulfonamides. CC {ECO:0000269|PubMed:10821855}. CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged CC heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) CC subunit. Interacts with BIRC6/bruce. {ECO:0000269|PubMed:15200957, CC ECO:0000269|PubMed:20566630}. CC -!- INTERACTION: CC P42574; O43823: AKAP8; NbExp=5; IntAct=EBI-524064, EBI-1237481; CC P42574; Q9Y243: AKT3; NbExp=2; IntAct=EBI-524064, EBI-296115; CC P42574; P05067: APP; NbExp=4; IntAct=EBI-524064, EBI-77613; CC P42574; P54252: ATXN3; NbExp=9; IntAct=EBI-524064, EBI-946046; CC P42574; P55212: CASP6; NbExp=2; IntAct=EBI-524064, EBI-718729; CC P42574; P55211: CASP9; NbExp=2; IntAct=EBI-524064, EBI-516799; CC P42574; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-524064, EBI-25840379; CC P42574; P42858: HTT; NbExp=9; IntAct=EBI-524064, EBI-466029; CC P42574; Q00987: MDM2; NbExp=2; IntAct=EBI-524064, EBI-389668; CC P42574; O60551: NMT2; NbExp=2; IntAct=EBI-524064, EBI-3920273; CC P42574; P09874: PARP1; NbExp=2; IntAct=EBI-524064, EBI-355676; CC P42574; Q5JUK2: SOHLH1; NbExp=3; IntAct=EBI-524064, EBI-12288855; CC P42574; P10599: TXN; NbExp=6; IntAct=EBI-524064, EBI-594644; CC P42574; Q9BYP7: WNK3; NbExp=2; IntAct=EBI-524064, EBI-1182602; CC P42574; P98170: XIAP; NbExp=4; IntAct=EBI-524064, EBI-517127; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15003516}. CC -!- TISSUE SPECIFICITY: Highly expressed in lung, spleen, heart, liver and CC kidney. Moderate levels in brain and skeletal muscle, and low in CC testis. Also found in many cell lines, highest expression in cells of CC the immune system. {ECO:0000269|PubMed:7983002}. CC -!- PTM: Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 CC generates the two active subunits (PubMed:7596430, PubMed:8755496, CC PubMed:35338844, PubMed:35446120). Additional processing of the CC propeptides is likely due to the autocatalytic activity of the CC activated protease (PubMed:7596430, PubMed:8755496). Active CC heterodimers between the small subunit of caspase-7 protease and the CC large subunit of caspase-3 also occur and vice versa (PubMed:7596430, CC PubMed:8755496). {ECO:0000269|PubMed:35338844, CC ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:7596430, CC ECO:0000269|PubMed:8755496}. CC -!- PTM: S-nitrosylated on its catalytic site cysteine in unstimulated CC human cell lines and denitrosylated upon activation of the Fas CC apoptotic pathway, associated with an increase in intracellular caspase CC activity. Fas therefore activates caspase-3 not only by inducing the CC cleavage of the caspase zymogen to its active subunits, but also by CC stimulating the denitrosylation of its active site thiol. CC {ECO:0000269|PubMed:10213689}. CC -!- PTM: (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CC CASP3 processing, preventing CASP3 activation and ability to recognize CC and cleave substrates. {ECO:0000269|PubMed:35338844, CC ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36423631}. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/casp3/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U13737; AAA65015.1; -; mRNA. DR EMBL; U13738; AAB60355.1; -; mRNA. DR EMBL; U26943; AAA74929.1; -; mRNA. DR EMBL; AJ413269; CAC88866.1; -; mRNA. DR EMBL; AK291337; BAF84026.1; -; mRNA. DR EMBL; AY219866; AAO25654.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04673.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04674.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04675.1; -; Genomic_DNA. DR EMBL; BC016926; AAH16926.1; -; mRNA. DR CCDS; CCDS3836.1; -. DR PIR; A55315; A55315. DR RefSeq; NP_004337.2; NM_004346.3. DR RefSeq; NP_116786.1; NM_032991.2. DR RefSeq; XP_011530603.1; XM_011532301.1. DR PDB; 1CP3; X-ray; 2.30 A; A/B=1-277. DR PDB; 1GFW; X-ray; 2.80 A; A=29-175, B=181-277. DR PDB; 1I3O; X-ray; 2.70 A; A/C=1-175, B/D=176-277. DR PDB; 1NME; X-ray; 1.60 A; A=29-174, B=186-277. DR PDB; 1NMQ; X-ray; 2.40 A; A/B=29-277. DR PDB; 1NMS; X-ray; 1.70 A; A/B=29-277. DR PDB; 1PAU; X-ray; 2.50 A; A=29-175, B=176-277. DR PDB; 1QX3; X-ray; 1.90 A; A=29-277. DR PDB; 1RE1; X-ray; 2.50 A; A=29-175, B=176-277. DR PDB; 1RHJ; X-ray; 2.20 A; A/C=29-175, B/D=176-277. DR PDB; 1RHK; X-ray; 2.50 A; A=29-175, B=176-277. DR PDB; 1RHM; X-ray; 2.50 A; A/C=29-175, B/D=176-277. DR PDB; 1RHQ; X-ray; 3.00 A; A/D=29-175, B/E=176-277. DR PDB; 1RHR; X-ray; 3.00 A; A=29-175, B=176-277. DR PDB; 1RHU; X-ray; 2.51 A; A=29-175, B=176-277. DR PDB; 2C1E; X-ray; 1.77 A; A=29-175, B=176-277. DR PDB; 2C2K; X-ray; 1.87 A; A=29-175, B=176-277. DR PDB; 2C2M; X-ray; 1.94 A; A=29-175, B=176-277. DR PDB; 2C2O; X-ray; 2.45 A; A=29-175, B=176-277. DR PDB; 2CDR; X-ray; 1.70 A; A=29-175, B=176-277. DR PDB; 2CJX; X-ray; 1.70 A; A=29-175, B=176-277. DR PDB; 2CJY; X-ray; 1.67 A; A=29-175, B=176-277. DR PDB; 2CNK; X-ray; 1.75 A; A=29-175, B=176-277. DR PDB; 2CNL; X-ray; 1.67 A; A=29-175, B=176-277. DR PDB; 2CNN; X-ray; 1.70 A; A=29-175, B=176-277. DR PDB; 2CNO; X-ray; 1.95 A; A=29-175, B=176-277. DR PDB; 2DKO; X-ray; 1.06 A; A=29-174, B=175-277. DR PDB; 2H5I; X-ray; 1.69 A; A=29-174, B=184-277. DR PDB; 2H5J; X-ray; 2.00 A; A/C=29-174, B/D=184-277. DR PDB; 2H65; X-ray; 2.30 A; A/C=29-174, B/D=184-277. DR PDB; 2J30; X-ray; 1.40 A; A=29-277. DR PDB; 2J31; X-ray; 1.50 A; A=29-277. DR PDB; 2J32; X-ray; 1.30 A; A=29-277. DR PDB; 2J33; X-ray; 2.00 A; A=29-277. DR PDB; 2XYG; X-ray; 1.54 A; A=29-174, B=185-277. DR PDB; 2XYH; X-ray; 1.89 A; A=29-174, B=185-277. DR PDB; 2XYP; X-ray; 1.86 A; A=29-174, B=185-277. DR PDB; 2XZD; X-ray; 2.10 A; A/C=27-175, B/D=176-277. DR PDB; 2XZT; X-ray; 2.70 A; A/C=29-175, B/D=176-277. DR PDB; 2Y0B; X-ray; 2.10 A; A/C=29-175, B/D=176-277. DR PDB; 3DEH; X-ray; 2.50 A; A/B/C/D=29-277. DR PDB; 3DEI; X-ray; 2.80 A; A/B/C/D=29-277. DR PDB; 3DEJ; X-ray; 2.60 A; A/B/C/D=29-277. DR PDB; 3DEK; X-ray; 2.40 A; A/B/C/D=29-277. DR PDB; 3EDQ; X-ray; 1.61 A; A/C=29-175, B/D=176-277. DR PDB; 3GJQ; X-ray; 2.60 A; A/C=29-175, B/D=176-277. DR PDB; 3GJR; X-ray; 2.20 A; A/C=29-175, B/D=176-277. DR PDB; 3GJS; X-ray; 1.90 A; A/C=29-175, B/D=176-277. DR PDB; 3GJT; X-ray; 2.20 A; A/C=29-175, B/D=176-277. DR PDB; 3H0E; X-ray; 2.00 A; A/B=29-277. DR PDB; 3ITN; X-ray; 1.63 A; A=29-277. DR PDB; 3KJF; X-ray; 2.00 A; A=29-175, B=176-277. DR PDB; 3PCX; X-ray; 1.50 A; A=29-277. DR PDB; 3PD0; X-ray; 2.00 A; A=29-277. DR PDB; 3PD1; X-ray; 1.62 A; A=29-277. DR PDB; 4DCJ; X-ray; 1.70 A; A/D=29-175, B/E=176-277. DR PDB; 4DCO; X-ray; 1.70 A; A/D=29-175, B/E=176-277. DR PDB; 4DCP; X-ray; 1.70 A; A/D=29-175, B/E=176-277. DR PDB; 4EHA; X-ray; 1.70 A; A/C=1-277. DR PDB; 4EHD; X-ray; 1.58 A; A=1-277. DR PDB; 4EHF; X-ray; 1.66 A; A=1-277. DR PDB; 4EHH; X-ray; 1.78 A; A=1-277. DR PDB; 4EHK; X-ray; 1.67 A; A/C=1-277. DR PDB; 4EHL; X-ray; 1.80 A; A/C=1-277. DR PDB; 4EHN; X-ray; 1.69 A; A=1-277. DR PDB; 4JJE; X-ray; 1.48 A; A=29-277. DR PDB; 4JQY; X-ray; 2.50 A; A/B=34-277. DR PDB; 4JQZ; X-ray; 2.89 A; A/B=34-277. DR PDB; 4JR0; X-ray; 1.80 A; A/B=34-277. DR PDB; 4PRY; X-ray; 1.70 A; A=1-277. DR PDB; 4PS0; X-ray; 1.63 A; A/B=1-277. DR PDB; 4QTX; X-ray; 1.97 A; A=1-277. DR PDB; 4QTY; X-ray; 1.60 A; A=29-277. DR PDB; 4QU0; X-ray; 1.95 A; A=1-277. DR PDB; 4QU5; X-ray; 1.91 A; A=1-277. DR PDB; 4QU8; X-ray; 1.72 A; A=1-277. DR PDB; 4QU9; X-ray; 1.56 A; A=1-277. DR PDB; 4QUA; X-ray; 1.89 A; A=1-277. DR PDB; 4QUB; X-ray; 1.69 A; A=1-277. DR PDB; 4QUD; X-ray; 2.00 A; A/B=1-277. DR PDB; 4QUE; X-ray; 1.84 A; A/C=1-277. DR PDB; 4QUG; X-ray; 1.92 A; A/C=1-277. DR PDB; 4QUH; X-ray; 1.76 A; A/C=1-277. DR PDB; 4QUI; X-ray; 1.76 A; A/B=1-277. DR PDB; 4QUJ; X-ray; 1.50 A; A=1-277. DR PDB; 4QUL; X-ray; 1.90 A; A/C=1-277. DR PDB; 5I9B; X-ray; 1.80 A; A=1-277. DR PDB; 5I9T; X-ray; 1.95 A; A/C=1-277. DR PDB; 5IAB; X-ray; 1.79 A; A/C=1-277. DR PDB; 5IAE; X-ray; 1.55 A; A/C=1-277. DR PDB; 5IAG; X-ray; 1.98 A; A=1-277. DR PDB; 5IAJ; X-ray; 1.58 A; A=1-277. DR PDB; 5IAK; X-ray; 1.82 A; A=1-277. DR PDB; 5IAN; X-ray; 2.70 A; A=1-277. DR PDB; 5IAR; X-ray; 1.76 A; A=1-277. DR PDB; 5IAS; X-ray; 1.54 A; A=1-277. DR PDB; 5IBC; X-ray; 1.66 A; A=1-277. DR PDB; 5IBP; X-ray; 1.38 A; A=1-277. DR PDB; 5IBR; X-ray; 1.74 A; A/C=1-277. DR PDB; 5IC4; X-ray; 2.65 A; A/C/E/G=1-175, B/D/F/H=176-276. DR PDB; 7XN4; EM; 3.35 A; A/C=1-277. DR PDB; 7XN5; EM; 3.18 A; A/C=1-277. DR PDB; 7XN6; EM; 3.45 A; A/C=1-277. DR PDBsum; 1CP3; -. DR PDBsum; 1GFW; -. DR PDBsum; 1I3O; -. DR PDBsum; 1NME; -. DR PDBsum; 1NMQ; -. DR PDBsum; 1NMS; -. DR PDBsum; 1PAU; -. DR PDBsum; 1QX3; -. DR PDBsum; 1RE1; -. DR PDBsum; 1RHJ; -. DR PDBsum; 1RHK; -. DR PDBsum; 1RHM; -. DR PDBsum; 1RHQ; -. DR PDBsum; 1RHR; -. DR PDBsum; 1RHU; -. DR PDBsum; 2C1E; -. DR PDBsum; 2C2K; -. DR PDBsum; 2C2M; -. DR PDBsum; 2C2O; -. DR PDBsum; 2CDR; -. DR PDBsum; 2CJX; -. DR PDBsum; 2CJY; -. DR PDBsum; 2CNK; -. DR PDBsum; 2CNL; -. DR PDBsum; 2CNN; -. DR PDBsum; 2CNO; -. DR PDBsum; 2DKO; -. DR PDBsum; 2H5I; -. DR PDBsum; 2H5J; -. DR PDBsum; 2H65; -. DR PDBsum; 2J30; -. DR PDBsum; 2J31; -. DR PDBsum; 2J32; -. DR PDBsum; 2J33; -. DR PDBsum; 2XYG; -. DR PDBsum; 2XYH; -. DR PDBsum; 2XYP; -. DR PDBsum; 2XZD; -. DR PDBsum; 2XZT; -. DR PDBsum; 2Y0B; -. DR PDBsum; 3DEH; -. DR PDBsum; 3DEI; -. DR PDBsum; 3DEJ; -. DR PDBsum; 3DEK; -. DR PDBsum; 3EDQ; -. DR PDBsum; 3GJQ; -. DR PDBsum; 3GJR; -. DR PDBsum; 3GJS; -. DR PDBsum; 3GJT; -. DR PDBsum; 3H0E; -. DR PDBsum; 3ITN; -. DR PDBsum; 3KJF; -. DR PDBsum; 3PCX; -. DR PDBsum; 3PD0; -. DR PDBsum; 3PD1; -. DR PDBsum; 4DCJ; -. DR PDBsum; 4DCO; -. DR PDBsum; 4DCP; -. DR PDBsum; 4EHA; -. DR PDBsum; 4EHD; -. DR PDBsum; 4EHF; -. DR PDBsum; 4EHH; -. DR PDBsum; 4EHK; -. DR PDBsum; 4EHL; -. DR PDBsum; 4EHN; -. DR PDBsum; 4JJE; -. DR PDBsum; 4JQY; -. DR PDBsum; 4JQZ; -. DR PDBsum; 4JR0; -. DR PDBsum; 4PRY; -. DR PDBsum; 4PS0; -. DR PDBsum; 4QTX; -. DR PDBsum; 4QTY; -. DR PDBsum; 4QU0; -. DR PDBsum; 4QU5; -. DR PDBsum; 4QU8; -. DR PDBsum; 4QU9; -. DR PDBsum; 4QUA; -. DR PDBsum; 4QUB; -. DR PDBsum; 4QUD; -. DR PDBsum; 4QUE; -. DR PDBsum; 4QUG; -. DR PDBsum; 4QUH; -. DR PDBsum; 4QUI; -. DR PDBsum; 4QUJ; -. DR PDBsum; 4QUL; -. DR PDBsum; 5I9B; -. DR PDBsum; 5I9T; -. DR PDBsum; 5IAB; -. DR PDBsum; 5IAE; -. DR PDBsum; 5IAG; -. DR PDBsum; 5IAJ; -. DR PDBsum; 5IAK; -. DR PDBsum; 5IAN; -. DR PDBsum; 5IAR; -. DR PDBsum; 5IAS; -. DR PDBsum; 5IBC; -. DR PDBsum; 5IBP; -. DR PDBsum; 5IBR; -. DR PDBsum; 5IC4; -. DR PDBsum; 7XN4; -. DR PDBsum; 7XN5; -. DR PDBsum; 7XN6; -. DR AlphaFoldDB; P42574; -. DR EMDB; EMD-33310; -. DR EMDB; EMD-33311; -. DR EMDB; EMD-33312; -. DR SMR; P42574; -. DR BioGRID; 107286; 129. DR ComplexPortal; CPX-970; Caspase-3 complex. DR DIP; DIP-268N; -. DR ELM; P42574; -. DR IntAct; P42574; 65. DR MINT; P42574; -. DR STRING; 9606.ENSP00000311032; -. DR BindingDB; P42574; -. DR ChEMBL; CHEMBL2334; -. DR DrugBank; DB08498; (1S)-1-(3-chlorophenyl)-2-oxo-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate. DR DrugBank; DB08497; (1S)-2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate. DR DrugBank; DB08213; 1-METHYL-5-(2-PHENOXYMETHYL-PYRROLIDINE-1-SULFONYL)-1H-INDOLE-2,3-DIONE. DR DrugBank; DB06862; 2-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC ACID. DR DrugBank; DB08251; 4-[5-(2-CARBOXY-1-FORMYL-ETHYLCARBAMOYL)-PYRIDIN-3-YL]-BENZOIC ACID. DR DrugBank; DB03124; 5-[4-(1-Carboxymethyl-2-Oxo-Propylcarbamoyl)-Benzylsulfamoyl]-2-Hydroxy-Benzoic Acid. DR DrugBank; DB08229; [N-(3-dibenzylcarbamoyl-oxiranecarbonyl)-hydrazino]-acetic acid. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB05408; Emricasan. DR DrugBank; DB13751; Glycyrrhizic acid. DR DrugBank; DB06255; Incadronic acid. DR DrugBank; DB07696; methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxopentanoate. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB08499; N-[3-(2-fluoroethoxy)phenyl]-N'-(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-6-yl)butanediamide. DR DrugBank; DB12843; Oleandrin. DR DrugBank; DB13048; PAC-1. DR DrugBank; DB00282; Pamidronic acid. DR DrugBank; DB12709; Tributyrin. DR DrugCentral; P42574; -. DR GuidetoPHARMACOLOGY; 1619; -. DR MEROPS; C14.003; -. DR TCDB; 8.A.217.1.1; the apoptosis cell death regulator (acdr) family. DR GlyGen; P42574; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P42574; -. DR MetOSite; P42574; -. DR PhosphoSitePlus; P42574; -. DR BioMuta; CASP3; -. DR DMDM; 77416852; -. DR OGP; P42574; -. DR CPTAC; CPTAC-5907; -. DR EPD; P42574; -. DR jPOST; P42574; -. DR MassIVE; P42574; -. DR MaxQB; P42574; -. DR PaxDb; 9606-ENSP00000311032; -. DR PeptideAtlas; P42574; -. DR ProteomicsDB; 55518; -. DR Pumba; P42574; -. DR ABCD; P42574; 3 sequenced antibodies. DR Antibodypedia; 1222; 2874 antibodies from 54 providers. DR CPTC; P42574; 1 antibody. DR DNASU; 836; -. DR Ensembl; ENST00000308394.9; ENSP00000311032.4; ENSG00000164305.20. DR Ensembl; ENST00000523916.5; ENSP00000428929.1; ENSG00000164305.20. DR Ensembl; ENST00000700100.1; ENSP00000514797.1; ENSG00000164305.20. DR Ensembl; ENST00000700101.1; ENSP00000514798.1; ENSG00000164305.20. DR GeneID; 836; -. DR KEGG; hsa:836; -. DR MANE-Select; ENST00000308394.9; ENSP00000311032.4; NM_004346.4; NP_004337.2. DR UCSC; uc003iwh.3; human. DR AGR; HGNC:1504; -. DR CTD; 836; -. DR DisGeNET; 836; -. DR GeneCards; CASP3; -. DR HGNC; HGNC:1504; CASP3. DR HPA; ENSG00000164305; Low tissue specificity. DR MIM; 600636; gene. DR neXtProt; NX_P42574; -. DR OpenTargets; ENSG00000164305; -. DR PharmGKB; PA26087; -. DR VEuPathDB; HostDB:ENSG00000164305; -. DR eggNOG; KOG3573; Eukaryota. DR GeneTree; ENSGT00940000153232; -. DR HOGENOM; CLU_036904_2_0_1; -. DR InParanoid; P42574; -. DR OMA; EMGVCVI; -. DR OrthoDB; 2873736at2759; -. DR PhylomeDB; P42574; -. DR TreeFam; TF102023; -. DR BioCyc; MetaCyc:HS09058-MONOMER; -. DR BRENDA; 3.4.22.56; 2681. DR PathwayCommons; P42574; -. DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage. DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs. DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes. DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins. DR Reactome; R-HSA-111469; SMAC, XIAP-regulated apoptotic response. DR Reactome; R-HSA-140342; Apoptosis induced DNA fragmentation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-2028269; Signaling by Hippo. DR Reactome; R-HSA-205025; NADE modulates death signalling. DR Reactome; R-HSA-211736; Stimulation of the cell death response by PAK-2p34. DR Reactome; R-HSA-264870; Caspase-mediated cleavage of cytoskeletal proteins. DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins. DR Reactome; R-HSA-418889; Caspase activation via Dependence Receptors in the absence of ligand. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-5620971; Pyroptosis. DR SABIO-RK; P42574; -. DR SignaLink; P42574; -. DR SIGNOR; P42574; -. DR BioGRID-ORCS; 836; 19 hits in 1159 CRISPR screens. DR ChiTaRS; CASP3; human. DR EvolutionaryTrace; P42574; -. DR GeneWiki; Caspase_3; -. DR GenomeRNAi; 836; -. DR Pharos; P42574; Tchem. DR PRO; PR:P42574; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P42574; Protein. DR Bgee; ENSG00000164305; Expressed in jejunal mucosa and 158 other cell types or tissues. DR ExpressionAtlas; P42574; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0031264; C:death-inducing signaling complex; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:Ensembl. DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IEA:Ensembl. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IDA:UniProt. DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0005123; F:death receptor binding; IEA:Ensembl. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0016005; F:phospholipase A2 activator activity; IEA:Ensembl. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0061713; P:anterior neural tube closure; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IDA:UniProt. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:BHF-UCL. DR GO; GO:0007413; P:axonal fasciculation; IEA:Ensembl. DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl. DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl. DR GO; GO:0072734; P:cellular response to staurosporine; IMP:CAFA. DR GO; GO:0006974; P:DNA damage response; IEA:Ensembl. DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IDA:UniProtKB. DR GO; GO:0097194; P:execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl. DR GO; GO:0034349; P:glial cell apoptotic process; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProt. DR GO; GO:0008627; P:intrinsic apoptotic signaling pathway in response to osmotic stress; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IBA:GO_Central. DR GO; GO:0007611; P:learning or memory; IEA:Ensembl. DR GO; GO:0071887; P:leukocyte apoptotic process; IEA:Ensembl. DR GO; GO:0001554; P:luteolysis; IEA:Ensembl. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IEA:Ensembl. DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl. DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:FlyBase. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IDA:MGI. DR GO; GO:0030220; P:platelet formation; TAS:UniProtKB. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0140639; P:positive regulation of pyroptosis; IDA:UniProt. DR GO; GO:0030163; P:protein catabolic process; IDA:UniProt. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. DR GO; GO:0016485; P:protein processing; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0070269; P:pyroptosis; IDA:UniProt. DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB. DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl. DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0034612; P:response to tumor necrosis factor; TAS:BHF-UCL. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl. DR CDD; cd00032; CASc; 1. DR Gene3D; 3.40.50.1460; -; 1. DR InterPro; IPR029030; Caspase-like_dom_sf. DR InterPro; IPR033139; Caspase_cys_AS. DR InterPro; IPR016129; Caspase_his_AS. DR InterPro; IPR011600; Pept_C14_caspase. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR001309; Pept_C14_p20. DR InterPro; IPR015917; Pept_C14A. DR PANTHER; PTHR10454; CASPASE; 1. DR PANTHER; PTHR10454:SF198; CASPASE-3; 1. DR Pfam; PF00656; Peptidase_C14; 1. DR PRINTS; PR00376; IL1BCENZYME. DR SMART; SM00115; CASc; 1. DR SUPFAM; SSF52129; Caspase-like; 1. DR PROSITE; PS01122; CASPASE_CYS; 1. DR PROSITE; PS01121; CASPASE_HIS; 1. DR PROSITE; PS50207; CASPASE_P10; 1. DR PROSITE; PS50208; CASPASE_P20; 1. DR Genevisible; P42574; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Cytoplasm; Direct protein sequencing; KW Hydrolase; Phosphoprotein; Protease; Reference proteome; S-nitrosylation; KW Thiol protease; Zymogen. FT PROPEP 1..9 FT /evidence="ECO:0000305|PubMed:23650375" FT /id="PRO_0000004569" FT PROPEP 10..28 FT /evidence="ECO:0000269|PubMed:7596430, FT ECO:0000305|PubMed:23650375" FT /id="PRO_0000004570" FT CHAIN 29..175 FT /note="Caspase-3 subunit p17" FT /evidence="ECO:0000305|PubMed:23650375, FT ECO:0000305|PubMed:7596430, ECO:0000305|PubMed:8755496" FT /id="PRO_0000004571" FT CHAIN 176..277 FT /note="Caspase-3 subunit p12" FT /evidence="ECO:0000305|PubMed:23650375, FT ECO:0000305|PubMed:7596430, ECO:0000305|PubMed:8755496" FT /id="PRO_0000004572" FT ACT_SITE 121 FT /evidence="ECO:0000250|UniProtKB:P29466" FT ACT_SITE 163 FT /evidence="ECO:0000250|UniProtKB:P29466" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT MOD_RES 11 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P70677" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 163 FT /note="S-nitrosocysteine; in inhibited form" FT /evidence="ECO:0000269|PubMed:10213689" FT MOD_RES 207 FT /note="(Microbial infection) ADP-riboxanated arginine" FT /evidence="ECO:0000269|PubMed:35338844, FT ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36423631" FT VARIANT 22 FT /note="H -> R (in dbSNP:rs35578277)" FT /id="VAR_048616" FT VARIANT 190 FT /note="E -> D (in dbSNP:rs1049210)" FT /evidence="ECO:0000269|PubMed:15003516, FT ECO:0000269|PubMed:7596430, ECO:0000269|PubMed:7983002" FT /id="VAR_001401" FT MUTAGEN 9 FT /note="D->A: In P3-D3A mutant; abolished cleavage and FT activation, leading to prevent thiol protease activity; FT when associated with A-28 and A-175." FT /evidence="ECO:0000269|PubMed:23650375" FT MUTAGEN 28 FT /note="D->A: In P3-D3A mutant; abolished cleavage and FT activation, leading to prevent thiol protease activity; FT when associated with A-9 and A-175." FT /evidence="ECO:0000269|PubMed:23650375" FT MUTAGEN 175 FT /note="D->A: In P3-D3A mutant; abolished cleavage and FT activation, leading to prevent thiol protease activity; FT when associated with A-9 and A-28." FT /evidence="ECO:0000269|PubMed:23650375" FT MUTAGEN 207 FT /note="R->A: Abolished ADP-riboxanation by C.violaceum FT CopC." FT /evidence="ECO:0000269|PubMed:35446120, FT ECO:0000269|PubMed:36423631" FT CONFLICT 31..36 FT /note="ISLDNS -> MSWDTG (in Ref. 3; CAC88866)" FT /evidence="ECO:0000305" FT STRAND 41..51 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 57..59 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 67..80 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 84..90 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 93..105 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 108..110 FT /evidence="ECO:0007829|PDB:1I3O" FT STRAND 111..120 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 136..141 FT /evidence="ECO:0007829|PDB:2DKO" FT TURN 145..147 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 156..162 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:2DKO" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:1NMS" FT TURN 189..192 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 193..199 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:2DKO" FT TURN 209..211 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 214..226 FT /evidence="ECO:0007829|PDB:2DKO" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 232..246 FT /evidence="ECO:0007829|PDB:2DKO" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:2DKO" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:2DKO" SQ SEQUENCE 277 AA; 31608 MW; 2F35CD3BCF7FF64A CRC64; MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKND LTREEIVELM RDVSKEDHSK RSSFVCVLLS HGEEGIIFGT NGPVDLKKIT NFFRGDRCRS LTGKPKLFII QACRGTELDC GIETDSGVDD DMACHKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN RKVATEFESF SFDATFHAKK QIPCIVSMLT KELYFYH //