CASP6 (Homo sapiens)
Description [+]
- Synonyms: CASP6, MCH2
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-6 Precursor (CASP-6)(EC 3.4.22.59)(Apoptotic protease Mch-2) [Contains Caspase-6 subunit p18;Caspase-6 subunit p11] [Source:UniProtKB/Swiss-Prot;Acc:P55212]
- Family: CASPASE
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp6
- WIKI: CASP6-H_sapiens
References [+]
- Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family.
- Fernandes-Alnemri T, Litwack G, Alnemri ES
- We have developed a PCR approach to clone new apoptotic Ced-3/Ice-like cysteine protease genes. This approach uses degenerate oligonucleotides encoding the highly conserved pentapeptides QACRG and GSWFI that are present in all known apoptotic cysteine proteases. Using this approach, we have cloned a novel apoptotic gene from human Jurkat T lymphocytes. The new gene encodes a approximately 34-kilodalton protein that is highly homologous to human CPP32, Caenorhabditis elegans cell death protein CED-3, mammalian Ich-1 (Nedd2), and mammalian interleukin-1 beta converting enzyme. Because of its high homology to the C. elegans Ced-3 gene, we named the new gene mammalian Ced-3 homologue Mch2. Two Mch2 transcripts (Mch2 alpha, 1.7 kb; Mch2 beta, 1.4 kb) were detected in Jurkat T lymphocytes and other cell lines. We believe that the Mch2 alpha transcript encodes the full-length Mch2, whereas the Mch2 beta transcript encodes a shorter Mch2 isoform, probably as a result of alternative splicing. Like interleukin-1 beta converting enzyme and CPP32, recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity, as determined by its ability to cleave the fluorogenic peptide DEVD-AMC. CPP32 and Mch2 alpha can also cleave poly(ADP-ribose) polymerase in vitro, suggesting that these enzymes participate in poly(ADP-ribose) polymerase cleavage observed during cellular apoptosis. In addition, overexpression of recombinant Mch2 alpha, but not Mch2 beta, induces apoptosis in Sf9 insect cells. Our data suggest that Mch2 is a Ced-3/interleukin-1 beta converting enzyme-like cysteine protease and could be another important mediator of apoptosis in mammalian cells. Cancer Res. 1995 Jul 1;55(13):2737-42.
- References from Mouse ortholog(s):
- APP binds DR6 to trigger axon pruning and neuron death via distinct caspases.
- Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M
- Naturally occurring axonal pruning and neuronal cell death help to sculpt neuronal connections during development, but their mechanistic basis remains poorly understood. Here we report that beta-amyloid precursor protein (APP) and death receptor 6 (DR6, also known as TNFRSF21) activate a widespread caspase-dependent self-destruction program. DR6 is broadly expressed by developing neurons, and is required for normal cell body death and axonal pruning both in vivo and after trophic-factor deprivation in vitro. Unlike neuronal cell body apoptosis, which requires caspase 3, we show that axonal degeneration requires caspase 6, which is activated in a punctate pattern that parallels the pattern of axonal fragmentation. DR6 is activated locally by an inactive surface ligand(s) that is released in an active form after trophic-factor deprivation, and we identify APP as a DR6 ligand. Trophic-factor deprivation triggers the shedding of surface APP in a beta-secretase (BACE)-dependent manner. Loss- and gain-of-function studies support a model in which a cleaved amino-terminal fragment of APP (N-APP) binds DR6 and triggers degeneration. Genetic support is provided by a common neuromuscular junction phenotype in mutant mice. Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease. Nature. 2009 Feb 19;457(7232):981-9.
- Caspase 6 regulates B cell activation and differentiation into plasma cells.
- Watanabe C, Shu GL, Zheng TS, Flavell RA, Clark EA
- Caspase (Casp) family proteases regulate not only lymphocyte apoptosis but also lymphocyte activation and development. In this study, we show that Casp6 regulates B cell activation and differentiation into plasma cells by modifying cell cycle entry. B cells from Casp6 knockout (Casp6 KO) mice examined ex vivo have more cells in G(1) than wild-type B cells, and mitogen-induced G(1) entry of Casp6 KO B cells is much faster than that of wild-type B cells. Even so, S phase entry and proliferation are not increased in Casp6 KO B cells. Rather than proliferating, activated Casp6 KO B cells preferentially differentiate into syndecan-1(+) plasma cells and produce Abs. In Casp6 KO mice compared with WT mice, serum levels of IgG1, IgG2a, and IgG2b are increased and Ag-specific Ab responses are also enhanced along with increased percentages of syndecan-1(+) plasma cells. Casp6 may regulate both B cell activation and differentiation by modifying requirements for G(0) B cells to enter G(1). J Immunol. 2008 Nov 15;181(10):6810-9.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 45 | 288 |
Protein sequence [+]
CASP6 | Homo sapiens | 9606 | length:293
MSSASGLRRGHPAGGEENMTETDAFYKREMFDPAEKYKMDHRRRGIALIFNHERFFWHLT
LPERRGTCADRDNLTRRFSDLGFEVKCFNDLKAEELLLKIHEVSTVSHADADCFVCVFLS
HGEGNHIYAYDAKIEIQTLTGLFKGDKCHSLVGKPKIFIIQACRGNQHDVPVIPLDVVDN
QTEKLDTNITEVDAASVYTLPAGADFLMCYSVAEGYYSHRETVNGSWYIQDLCEMLGKYG
SSLEFTELLTLVNRKVSQRRVDFCKDPSAIGKKQVPCFASMLTKKLHFFPKSN
LPERRGTCADRDNLTRRFSDLGFEVKCFNDLKAEELLLKIHEVSTVSHADADCFVCVFLS
HGEGNHIYAYDAKIEIQTLTGLFKGDKCHSLVGKPKIFIIQACRGNQHDVPVIPLDVVDN
QTEKLDTNITEVDAASVYTLPAGADFLMCYSVAEGYYSHRETVNGSWYIQDLCEMLGKYG
SSLEFTELLTLVNRKVSQRRVDFCKDPSAIGKKQVPCFASMLTKKLHFFPKSN
Structure links:
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS01121
- Prosite motif and domain information: PS01122
- Profile motif and domain profile information: PS50207
- Profile motif and domain profile information: PS50208
- Interpro domain information: P55212
- PFAM domain and domain family information: P55212
- Protein 3D structures from PDB: 1MI9
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL003444-PA | orthology | Aedes |
| A_aegypti_AAEL012143-PA | orthology | Aedes |
| A_aegypti_AAEL014348-PA | orthology | Aedes |
| A_aegypti_AAEL003439-PA | orthology | Aedes |
| CASPS14 | orthology | Anopheles |
| CASPS1 | orthology | Anopheles |
| CASPS6 | orthology | Anopheles |
| CASPS3 | orthology | Anopheles |
| CASPS5 | orthology | Anopheles |
| CASPS7 | orthology | Anopheles |
| CASPS2 | orthology | Anopheles |
| CASPS8 | orthology | Anopheles |
| CASPS4 | orthology | Anopheles |
| NP_990057.1 | orthology | Chicken |
| CASP6 | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | orthology | Ciona |
| CASP6_BOVIN | orthology | Cow |
| CASP6 | orthology | Dog |
| decay | orthology | Fly |
| Ice | orthology | Fly |
| Dcp-1 | orthology | Fly |
| CASP6 | orthology | Fugu |
| CASP6 | orthology | Gasterosteus |
| CASP6 | orthology | Horse |
| CASP6 | orthology | Lyzard |
| CASP6 | orthology | Macaca |
| CASP6 (1 of 2) | orthology | Medaka |
| CASP6 (2 of 2) | orthology | Medaka |
| CASP6 | orthology | Monodelphis |
| Casp6 | orthology | Mouse |
| CASP6 | orthology | Orangutan |
| CASP6 | orthology | Ornithorhynchus |
| CASP6 | orthology | Rabbit |
| Casp6 | orthology | Rat |
| CASP6 | orthology | Tetraodon |
| casp6 | orthology | Xenopus |
| T_guttata_ENSTGUP00000016598 | orthology | Zebra finch |
| T_guttata_ENSTGUP00000004278 | orthology | Zebra finch |
| casp6 | orthology | Zebrafish |
| casp6l2 | orthology | Zebrafish |
| casp6l1 | orthology | Zebrafish |
| NP_989923.1 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000025905 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011503 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000028692 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000025743 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011493 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| NP_001039435.1 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| Q38JA9_CANFA | paralogy | Dog |
| CASP10 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP7 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| CASP7 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gorilla |
| CASP8 | paralogy | Gorilla |
| CASP8 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP3 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP7 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| CASP9 | paralogy | Medaka |
| Q56VC9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| CASP7 | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP8 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000005512 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP7 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp8 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| CASP10 | paralogy | Rabbit |
| R_norvegicus_ENSRNOP00000040783 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| casp10 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| CASP9 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000014729 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| casp8l1 | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | 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:0006917 | induction of apoptosis | biological_proccess | TAS |
| GO:0006508 | proteolysis | biological_proccess | IDA |
| GO:0002088 | lens development in camera-type eye | biological_proccess | IEA |
| GO:0034097 | response to cytokine stimulus | biological_proccess | IEA |
| GO:0042542 | response to hydrogen peroxide | biological_proccess | IEA |
| GO:0010243 | response to organic nitrogen | biological_proccess | IEA |
| GO:0009408 | response to heat | biological_proccess | IEA |
| GO:0010332 | response to gamma radiation | biological_proccess | IEA |
| GO:0009749 | response to glucose stimulus | biological_proccess | IEA |
| GO:0032355 | response to estradiol stimulus | biological_proccess | IEA |
| GO:0033574 | response to testosterone stimulus | biological_proccess | IEA |
| GO:0002525 | acute inflammatory response to non-antigenic stimulus | biological_proccess | IEA |
| GO:0010039 | response to iron ion | biological_proccess | IEA |
| GO:0043525 | positive regulation of neuron apoptosis | biological_proccess | IEA |
| GO:0046670 | positive regulation of retinal cell programmed cell death | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005737 | cytoplasm | cell_component | IEA |
| GO:0005634 | nucleus | cell_component | IEA |
| GO:0005829 | cytosol | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
miRNAs [+]
| miRNA | Regulation | Description | Pubmed |
|---|---|---|---|
| hsa-miR-125b | overexpression by mature mRNA mimics transfection | By using a 2.0-fold difference as the cut-off, there were 60 differentially expressed genes: 13 were up-regulated and 47 were down-regulated (SI Tables 1 and 2). | Ref. |
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000254866 * | OTTHUMP00000162742 * |
| OTTHUMT00000254867 | OTTHUMP00000162743 |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1507
- Gene related info from GeneCards [?] : CASP6
- Ensembl genome browser [?] : ENSG00000138794
- Expression info from Arrayexpress [?] : ENSG00000138794
- Protein expression from Protein Atlas: [?] ENSG00000138794
- Community gene edition from Wikigenes: [?] 839
- OMIM gene information: 601532
- OMIM disease information:
Click on [?] for more information.
