CASP3 (Homo sapiens)
Description [+]
- Synonyms: CASP3, CPP32, CPP32B, YAMA, APOPAIN
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-3 Precursor (CASP-3)(EC 3.4.22.56)(Apopain)(Cysteine protease CPP32)(CPP-32)(Yama protein)(SREBP cleavage activity 1)(SCA-1) [Contains Caspase-3 subunit p17;Caspase-3 subunit p12] [Source:UniProtKB/Swiss-Prot;Acc:P42574]
- Family: CASPASE
- Process: apoptosis,
- Pathways: intrinsic pathway, extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp3
- WIKI: CASP3-H_sapiens
References [+]
- CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
- Fernandes-Alnemri T, Litwack G, Alnemri ES
- We have cloned a novel apoptotic gene from human Jurkat T-lymphocytes. The new gene encodes a 32-kDa putative cysteine protease (CPP32) with significant homology to Caenorhabditis elegans cell death protein Ced-3, mammalian interleukin-1 beta-converting enzyme (ICE), and the product of the mouse nedd2 gene. The CPP32 transcript is highly expressed and most abundant in cell lines of lymphocytic origin. Overexpression of CPP32 or ICE in Sf9 insect cells resulted in apoptosis. In addition, coexpression of recombinant p20 and p11 derived from the parental full-length CPP32 sequence resulted in apoptosis in Sf9 cells. Our data suggest that similar to ICE, CPP32 is made of two subunits, p20 and p11, which form the active CPP32 complex. The apoptotic activity of CPP32 and its high expression in lymphocytes suggest that CPP32 is an important mediator of apoptosis in the immune system. J Biol Chem. 1994 Dec 9;269(49):30761-4.
- References from Mouse ortholog(s):
- Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.
- Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA
- Programmed cell death (apoptosis) is a prominent feature of the development of the immune and nervous systems. The identification of the Caenorhabditis elegans cell death gene, ced-3, as a prototype of the interleukin-1beta converting enzyme (ICE) protease family has led to extensive evidence implicating these enzymes in apoptosis. Among the ten or more members of the ICE protease family, CPP32/yama/apopain exhibits the highest similarity to CED-3 in both sequence homology and substrate specificity. To analyse its function in vivo, we generated CPP32-deficient mice by homologous recombination. These mice, born at a frequency lower than expected by mendelian genetics, were smaller than their littermates and died at 1-3 weeks of age. Although their thymocytes retained normal susceptibility to various apoptotic stimuli, brain development in CPP32-deficient mice was profoundly affected, and discernible by embryonic day 12, resulting in a variety of hyperplasias and disorganized cell deployment. These supernumerary cells were postmitotic and terminally differentiated by the postnatal stage. Pyknotic clusters at sites of major morphogenetic change during normal brain development were not observed in the mutant embryos, indicating decreased apoptosis in the absence of CPP32. Thus CPP32 is shown to play a critical role during morphogenetic cell death in the mammalian brain. Nature. 1996 Nov 28;384(6607):368-72.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 45 | 275 |
Protein sequence [+]
CASP3 | Homo sapiens | 9606 | length:277
MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
Structure links:
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS01121
- Prosite motif and domain information: PS01122
- Profile motif and domain profile information: PS50208
- Profile motif and domain profile information: PS50207
- Interpro domain information: P42574
- PFAM domain and domain family information: P42574
- Protein 3D structures from PDB: 3DEJ 3DEK 3DEH 3DEI 2J32 2J33 2C2M 2C2O 2CDR 2CJX 2CJY 2CNK 2CNL 2CNN 2CNO 2DKO 2H5I 2H5J 2H65 2J30 2J31 1PAU 1QX3 1RE1 1RHJ 1RHK 1RHM 1RHQ 1RHR 1RHU 2C1E 2C2K 1CP3 1GFW 1I3O 1NME 1NMQ 1NMS
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL003439-PA | orthology | Aedes |
| A_aegypti_AAEL003444-PA | orthology | Aedes |
| A_aegypti_AAEL012143-PA | orthology | Aedes |
| A_aegypti_AAEL014348-PA | orthology | Aedes |
| CASPS4 | orthology | Anopheles |
| CASPS3 | orthology | Anopheles |
| CASPS14 | orthology | Anopheles |
| CASPS7 | orthology | Anopheles |
| CASPS6 | orthology | Anopheles |
| CASPS5 | orthology | Anopheles |
| CASPS11 | orthology | Anopheles |
| CASPS8 | orthology | Anopheles |
| CASPS1 | orthology | Anopheles |
| CASPS2 | orthology | Anopheles |
| NP_990056.1 | orthology | Chicken |
| CASP3_PANTR | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000011493 | orthology | Ciona |
| C_intestinalis_ENSCINP00000011503 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025743 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025905 | orthology | Ciona |
| C_intestinalis_ENSCINP00000028692 | orthology | Ciona |
| CASP3_BOVIN | orthology | Cow |
| CASP3_CANFA | orthology | Dog |
| Dcp-1 | orthology | Fly |
| decay | orthology | Fly |
| Ice | orthology | Fly |
| NP_001027871.1 | orthology | Fugu |
| CASP3 (4 of 4) | orthology | Gasterosteus |
| CASP3 (3 of 4) | orthology | Gasterosteus |
| CASP3 (2 of 4) | orthology | Gasterosteus |
| CASP3 (1 of 4) | orthology | Gasterosteus |
| Q3S2Z5_HORSE | orthology | Horse |
| CASP3 | orthology | Lyzard |
| Q8SPU2_MACMU | orthology | Macaca |
| M_mulatta_ENSMMUP00000033547 | orthology | Macaca |
| Q8JIS8_ORYLA | orthology | Medaka |
| Q8JIS9_ORYLA | orthology | Medaka |
| M_domestica_ENSMODP00000005512 | orthology | Monodelphis |
| NP_001033059.1 | orthology | Monodelphis |
| NP_001033061.1 | orthology | Monodelphis |
| Casp3 | orthology | Mouse |
| CASP3 | orthology | Orangutan |
| CASP3 | orthology | Ornithorhynchus |
| CASP3 | orthology | Rabbit |
| Casp3 | orthology | Rat |
| R_norvegicus_ENSRNOP00000040783 | orthology | Rat |
| CASP3 | orthology | Tetraodon |
| CASP3 | orthology | Xenopus |
| CASP3 | orthology | Zebra finch |
| casp3a | orthology | Zebrafish |
| casp3b | orthology | Zebrafish |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| CASP7 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| CASP6_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP7 | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| CASP6 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP2 | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP9 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| CASP8 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP6 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP7 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP7 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP9 | paralogy | Medaka |
| CASP7 | paralogy | Medaka |
| CASP9 | paralogy | Monodelphis |
| CASP6 | paralogy | Monodelphis |
| CASP7 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp8 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| CASP9 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| CASP6 | paralogy | Rabbit |
| Casp6 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| casp10 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| casp6 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000014729 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp6l1 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0034612 | response to tumor necrosis factor | biological_proccess | TAS |
| GO:0001836 | release of cytochrome c from mitochondria | biological_proccess | IEA |
| GO:0006309 | DNA fragmentation during apoptosis | biological_proccess | IEA |
| GO:0006974 | response to DNA damage stimulus | biological_proccess | IEA |
| GO:0007605 | sensory perception of sound | biological_proccess | IEA |
| GO:0008625 | induction of apoptosis via death domain receptors | biological_proccess | IEA |
| GO:0008631 | induction of apoptosis by oxidative stress | biological_proccess | IEA |
| GO:0009611 | response to wounding | biological_proccess | IEA |
| GO:0043029 | T cell homeostasis | biological_proccess | IEA |
| GO:0045165 | cell fate commitment | biological_proccess | IEA |
| GO:0046007 | negative regulation of activated T cell proliferation | biological_proccess | IEA |
| GO:0051402 | neuron apoptosis | biological_proccess | IEA |
| GO:0030264 | nuclear fragmentation during apoptosis | biological_proccess | IMP |
| GO:0043066 | negative regulation of apoptosis | biological_proccess | IGI |
| GO:0030889 | negative regulation of B cell proliferation | biological_proccess | IEA |
| GO:0001782 | B cell homeostasis | biological_proccess | IEA |
| GO:0030216 | keratinocyte differentiation | biological_proccess | IEA |
| GO:0006508 | proteolysis | biological_proccess | IDA |
| GO:0007507 | heart development | biological_proccess | IEA |
| GO:0009411 | response to UV | biological_proccess | IEA |
| GO:0045736 | negative regulation of cyclin-dependent protein kinase activity | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | IEA |
| GO:0045786 | negative regulation of cell cycle | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0004861 | cyclin-dependent protein kinase inhibitor activity | mollecular_function | IEA |
| GO:0008233 | peptidase activity | mollecular_function | IDA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | TAS |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005829 | cytosol | cell_component | IDA |
| GO:0005737 | cytoplasm | cell_component | IEA |
| GO:0005654 | nucleoplasm | cell_component | EXP |
| GO:0005886 | plasma membrane | cell_component | EXP |
| GO:0005634 | nucleus | cell_component | IDA |
| GO:0005739 | mitochondrion | cell_component | IDA |
Check GO Evidence Codes here
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000257885 * | OTTHUMP00000165052 * |
| OTTHUMT00000257886 | OTTHUMP00000165053 |
| OTTHUMT00000257887 | OTTHUMP00000165054 |
| OTTHUMT00000257888 | OTTHUMP00000165055 |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1504
- Gene related info from GeneCards [?] : CASP3
- Ensembl genome browser [?] : ENSG00000164305
- Expression info from Arrayexpress [?] : ENSG00000164305
- Protein expression from Protein Atlas: [?] ENSG00000164305
- Community gene edition from Wikigenes: [?] 836
- OMIM gene information: 600636
- OMIM disease information:
Click on [?] for more information.
