Caspase-3

Details

Name
Caspase-3
Synonyms
  • 3.4.22.56
  • Apopain
  • CASP-3
  • CPP-32
  • CPP32
  • Cysteine protease CPP32
  • Protein Yama
  • SCA-1
  • SREBP cleavage activity 1
Gene Name
CASP3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016333|Caspase-3
MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
Number of residues
277
Molecular Weight
31607.58
Theoretical pI
6.51
GO Classification
Functions
aspartic-type endopeptidase activity / cyclin-dependent protein serine/threonine kinase inhibitor activity / cysteine-type endopeptidase activity / cysteine-type endopeptidase activity involved in apoptotic process / cysteine-type endopeptidase activity involved in execution phase of apoptosis / peptidase activity / phospholipase A2 activator activity
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / apoptotic DNA fragmentation / apoptotic process / apoptotic signaling pathway / B cell homeostasis / cell fate commitment / cellular component disassembly involved in execution phase of apoptosis / cellular response to DNA damage stimulus / cellular response to organic cyclic compound / erythrocyte differentiation / execution phase of apoptosis / extracellular matrix disassembly / extracellular matrix organization / extrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / glial cell apoptotic process / heart development / hippo signaling / hippocampus development / intrinsic apoptotic signaling pathway / keratinocyte differentiation / learning or memory / negative regulation of activated T cell proliferation / negative regulation of apoptotic process / negative regulation of B cell proliferation / negative regulation of cyclin-dependent protein serine/threonine kinase activity / neuron apoptotic process / neuron differentiation / neurotrophin TRK receptor signaling pathway / platelet formation / positive regulation of neuron apoptotic process / programmed cell death / proteolysis / regulation of cysteine-type endopeptidase activity involved in apoptotic process / response to amino acid / response to antibiotic / response to cobalt ion / response to drug / response to estradiol / response to glucocorticoid / response to glucose / response to hydrogen peroxide / response to hypoxia / response to lipopolysaccharide / response to nicotine / response to tumor necrosis factor / response to UV / response to X-ray / sensory perception of sound / T cell homeostasis / wound healing
Components
cytosol / death-inducing signaling complex / membrane raft / nucleoplasm / nucleus / plasma membrane
General Function
Phospholipase a2 activator activity
Specific Function
Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016334|Caspase-3 (CASP3)
ATGGAGAACACTGAAAACTCAGTGGATTCAAAATCCATTAAAAATTTGGAACCAAAGATC
ATACATGGAAGCGAATCAATGGACTCTGGAATATCCCTGGACAACAGTTATAAAATGGAT
TATCCTGAGATGGGTTTATGTATAATAATTAATAATAAGAATTTTCATAAAAGCACTGGA
ATGACATCTCGGTCTGGTACAGATGTCGATGCAGCAAACCTCAGGGAAACATTCAGAAAC
TTGAAATATGAAGTCAGGAATAAAAATGATCTTACACGTGAAGAAATTGTGGAATTGATG
CGTGATGTTTCTAAAGAAGATCACAGCAAAAGGAGCAGTTTTGTTTGTGTGCTTCTGAGC
CATGGTGAAGAAGGAATAATTTTTGGAACAAATGGACCTGTTGACCTGAAAAAAATAACA
AACTTTTTCAGAGGGGATCGTTGTAGAAGTCTAACTGGAAAACCCAAACTTTTCATTATT
CAGGCCTGCCGTGGTACAGAACTGGACTGTGGCATTGAGACAGACAGTGGTGTTGATGAT
GACATGGCGTGTCATAAAATACCAGTGGAGGCCGACTTCTTGTATGCATACTCCACAGCA
CCTGGTTATTATTCTTGGCGAAATTCAAAGGATGGCTCCTGGTTCATCCAGTCGCTTTGT
GCCATGCTGAAACAGTATGCCGACAAGCTTGAATTTATGCACATTCTTACCCGGGTTAAC
CGAAAGGTGGCAACAGAATTTGAGTCCTTTTCCTTTGACGCTACTTTTCATGCAAAGAAA
CAGATTCCATGTATTGTTTCCATGCTCACAAAAGAACTCTATTTTTATCACTAA
Chromosome Location
4
Locus
4q34
External Identifiers
ResourceLink
UniProtKB IDP42574
UniProtKB Entry NameCASP3_HUMAN
GenBank Protein ID561666
GenBank Gene IDU13737
GenAtlas IDCASP3
HGNC IDHGNC:1504
General References
  1. Fernandes-Alnemri T, Litwack G, Alnemri ES: 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. 1994 Dec 9;269(49):30761-4. [PubMed:7983002]
  2. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM: Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801-9. [PubMed:7774019]
  3. Pelletier M, Cartron PF, Delaval F, Meflah K, Vallette FM, Oliver L: Caspase 3 activation is controlled by a sequence located in the N-terminus of its large subunit. Biochem Biophys Res Commun. 2004 Mar 26;316(1):93-9. [PubMed:15003516]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.: Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. [PubMed:7596430]
  7. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES: In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9. [PubMed:8755496]
  8. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR: Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442-9. [PubMed:8696339]
  9. Mannick JB, Hausladen A, Liu L, Hess DT, Zeng M, Miao QX, Kane LS, Gow AJ, Stamler JS: Fas-induced caspase denitrosylation. Science. 1999 Apr 23;284(5414):651-4. [PubMed:10213689]
  10. Bartke T, Pohl C, Pyrowolakis G, Jentsch S: Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004 Jun 18;14(6):801-11. [PubMed:15200957]
  11. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  13. Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P: RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem. 2011 Apr 22;286(16):14628-38. doi: 10.1074/jbc.M110.195461. Epub 2011 Feb 28. [PubMed:21357690]
  14. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [PubMed:22223895]
  15. Rotonda J, Nicholson DW, Fazil KM, Gallant M, Gareau Y, Labelle M, Peterson EP, Rasper DM, Ruel R, Vaillancourt JP, Thornberry NA, Becker JW: The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat Struct Biol. 1996 Jul;3(7):619-25. [PubMed:8673606]
  16. Mittl PR, Di Marco S, Krebs JF, Bai X, Karanewsky DS, Priestle JP, Tomaselli KJ, Grutter MG: Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone. J Biol Chem. 1997 Mar 7;272(10):6539-47. [PubMed:9045680]
  17. Lee D, Long SA, Adams JL, Chan G, Vaidya KS, Francis TA, Kikly K, Winkler JD, Sung CM, Debouck C, Richardson S, Levy MA, DeWolf WE Jr, Keller PM, Tomaszek T, Head MS, Ryan MD, Haltiwanger RC, Liang PH, Janson CA, McDevitt PJ, Johanson K, Concha NO, Chan W, Abdel-Meguid SS, Badger AM, Lark MW, Nadeau DP, Suva LJ, Gowen M, Nuttall ME: Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. J Biol Chem. 2000 May 26;275(21):16007-14. [PubMed:10821855]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01017Minocyclineapproved, investigationalunknownnegative modulatorDetails
DB031245-[4-(1-Carboxymethyl-2-Oxo-Propylcarbamoyl)-Benzylsulfamoyl]-2-Hydroxy-Benzoic AcidexperimentalunknownDetails
DB05408EmricasaninvestigationalunknownDetails
DB068622-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC ACIDexperimentalunknownDetails
DB07696methyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxopentanoateexperimentalunknownDetails
DB082131-METHYL-5-(2-PHENOXYMETHYL-PYRROLIDINE-1-SULFONYL)-1H-INDOLE-2,3-DIONEexperimentalunknownDetails
DB08229[N-(3-DIBENZYLCARBAMOYL-OXIRANECARBONYL)-HYDRAZINO]-ACETIC ACIDexperimentalunknownDetails
DB082514-[5-(2-CARBOXY-1-FORMYL-ETHYLCARBAMOYL)-PYRIDIN-3-YL]-BENZOIC ACIDexperimentalunknownDetails
DB08497(1S)-2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetateexperimentalunknownDetails
DB08498(1S)-1-(3-chlorophenyl)-2-oxo-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetateexperimentalunknownDetails
DB08499N-[3-(2-fluoroethoxy)phenyl]-N'-(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-6-yl)butanediamideexperimentalunknownDetails
DB13751Glycyrrhizic acidapproved, experimentalyesantagonistDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknowninhibitordownregulatorDetails