CASP7 (Homo sapiens)
Description [+]
- Synonyms: CASP7, MCH3, CMH-1, ICE-LAP3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-7 Precursor (CASP-7)(EC 3.4.22.60)(ICE-like apoptotic protease 3)(ICE-LAP3)(Apoptotic protease Mch-3)(CMH-1) [Contains Caspase-7 subunit p20;Caspase-7 subunit p11] [Source:UniProtKB/Swiss-Prot;Acc:P55210]
- Family: CASPASE
- Process: apoptosis,
- Pathways: intrinsic pathway, extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp7
- WIKI: CASP7-H_sapiens
References [+]
- Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
- Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G, et al.
- Recent evidence suggests that mammalian cysteine proteases related to Caenorhabditis elegans CED-3 are key components of mammalian programmed cell death or apoptosis. We have shown recently that the CPP32 and Mch2 alpha cysteine proteases cleave the apoptotic markers poly(ADP-ribose) polymerase (PARP) and lamins, respectively. Here we report the cloning of a new Ced-3/interleukin 1 beta-converting enzyme-related gene, designated Mch3, that encodes a protein with the highest degree of homology to CPP32 compared to other family members. An alternatively spliced isoform, named Mch3 beta, was also identified. Bacterially expressed recombinant Mch3 has intrinsic autocatalytic/autoactivation activity. The specific activity of Mch3 alpha toward the peptide substrate DEVD-7-amino-4-methylcoumarin and PARP resembles that of CPP32. Like interleukin 1 beta-converting enzyme and CPP32, the active Mch3 alpha is made of two subunits derived from a precursor (proMch3 alpha). It was of interest that recombinant CPP32-p17 subunit can form an active heteromeric enzyme complex with recombinant Mch3 alpha-p12 subunit and vice versa, as determined by the ability of the heteromeric complexes to induce apoptosis in Sf9 cells. These data suggest that proMch3 alpha and proCPP32 can interact to form an active Mch3 alpha/CPP32 heteromeric complex. We also provide evidence that CPP32 can efficiently cleave proMch3 alpha, but not the opposite, suggesting that Mch3 alpha activation in vivo may depend in part on CPP32 activity. The high degree of conservation in structure and specific activity and the coexistence of Mch3 alpha and CPP32 in the same cell suggests that the PARP cleavage activity observed during apoptosis cannot solely be attributed to CPP32 but could also be an activity of Mch3 alpha. Cancer Res. 1995 Dec 15;55(24):6045-52.
- Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3.
- Juan TS, McNiece IK, Argento JM, Jenkins NA, Gilbert DJ, Copeland NG, Fletcher FA
- Cloning of interleukin-1 beta converting enzyme (ICE) and Caenorhabditis elegans death protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvement of ICE-like cysteine proteases in apoptosis. Several CED-3- and ICE-like cysteine proteases have been described, including Nedd2/Ich-1, CPP32 beta, Tx, ICErel3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32 beta that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and human Casp7, another member of this family of cysteine proteases. Mouse Casp7 encodes a putative 340-amino-acid polypeptide that contains all the known conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, and the residues required for substrate binding. Three RNA variants of human Casp7 were also cloned. Amino acid sequence analysis indicated that Casp7 shared high homology with CPP32 beta/Casp3 and Mch2/Casp6. Northern blot analysis demonstrated that a 2.6-kb Casp7 mRNA was expressed in various tissues except brain. Mouse interspecific backcross mapping allowed localization of Casp7 to the distal region of mouse chromosome 19, linked to Mxi1, Adra2a, and Aop1. Genomics. 1997 Feb 15;40(1):86-93.
- References from Mouse ortholog(s):
- Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3.
- Juan TS, McNiece IK, Argento JM, Jenkins NA, Gilbert DJ, Copeland NG, Fletcher FA
- Cloning of interleukin-1 beta converting enzyme (ICE) and Caenorhabditis elegans death protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvement of ICE-like cysteine proteases in apoptosis. Several CED-3- and ICE-like cysteine proteases have been described, including Nedd2/Ich-1, CPP32 beta, Tx, ICErel3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32 beta that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and human Casp7, another member of this family of cysteine proteases. Mouse Casp7 encodes a putative 340-amino-acid polypeptide that contains all the known conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, and the residues required for substrate binding. Three RNA variants of human Casp7 were also cloned. Amino acid sequence analysis indicated that Casp7 shared high homology with CPP32 beta/Casp3 and Mch2/Casp6. Northern blot analysis demonstrated that a 2.6-kb Casp7 mRNA was expressed in various tissues except brain. Mouse interspecific backcross mapping allowed localization of Casp7 to the distal region of mouse chromosome 19, linked to Mxi1, Adra2a, and Aop1. Genomics. 1997 Feb 15;40(1):86-93.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 101 | 334 |
Protein sequence [+]
CASP7 | Homo sapiens | 9606 | length:336
MDCVGWPPGRKWHLEKNTSCGGSSGICASYVTQMADDQGCIEEQGVEDSANEDSVDAKPD
RSSFVPSLFSKKKKNVTMRSIKTTRDRVPTYQYNMNFEKLGKCIIINNKNFDKVTGMGVR
NGTDKDAEALFKCFRSLGFDVIVYNDCSCAKMQDLLKKASEEDHTNAACFACILLSHGEE
NVIYGKDGVTPIKDLTAHFRGDRCKTLLEKPKLFFIQACRGTELDDGIQADSGPINDTDA
NPRYKIPVEADFLFAYSTVPGYYSWRSPGRGSWFVQALCSILEEHGKDLEIMQILTRVND
RVARHFESQSDDPHFHEKKQIPCVVSMLTKELYFSQ
RSSFVPSLFSKKKKNVTMRSIKTTRDRVPTYQYNMNFEKLGKCIIINNKNFDKVTGMGVR
NGTDKDAEALFKCFRSLGFDVIVYNDCSCAKMQDLLKKASEEDHTNAACFACILLSHGEE
NVIYGKDGVTPIKDLTAHFRGDRCKTLLEKPKLFFIQACRGTELDDGIQADSGPINDTDA
NPRYKIPVEADFLFAYSTVPGYYSWRSPGRGSWFVQALCSILEEHGKDLEIMQILTRVND
RVARHFESQSDDPHFHEKKQIPCVVSMLTKELYFSQ
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: P55210
- PFAM domain and domain family information: P55210
- Protein 3D structures from PDB: 2QLF 2QLJ 2QLB 2QL7 2QL9 1SHL 2QL5 1K86 1K88 1KMC 1MIA 1SHJ 1I4O 1I51 1F1J 1GQF
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_AAEL014348-PA | orthology | Aedes |
| A_aegypti_AAEL003444-PA | orthology | Aedes |
| A_aegypti_AAEL012143-PA | orthology | Aedes |
| CASPS11 | orthology | Anopheles |
| CASPS6 | orthology | Anopheles |
| CASPS5 | orthology | Anopheles |
| CASPS3 | orthology | Anopheles |
| CASPS7 | orthology | Anopheles |
| A_gambiae_AGAP012945-PA | orthology | Anopheles |
| CASPS8 | orthology | Anopheles |
| CASPS4 | orthology | Anopheles |
| CASPS14 | orthology | Anopheles |
| CASP7 | orthology | Chicken |
| CASP7 | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000011493 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025905 | orthology | Ciona |
| C_intestinalis_ENSCINP00000011503 | orthology | Ciona |
| C_intestinalis_ENSCINP00000028692 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025743 | orthology | Ciona |
| IPI00689801.3 | orthology | Cow |
| CASP7 | orthology | Dog |
| decay | orthology | Fly |
| Ice | orthology | Fly |
| Dcp-1 | orthology | Fly |
| CASP7 | orthology | Fugu |
| CASP7 | orthology | Gasterosteus |
| CASP7 | orthology | Gorilla |
| CASP7 | orthology | Horse |
| CASP7 | orthology | Lyzard |
| CASP7 | orthology | Macaca |
| CASP7 | orthology | Medaka |
| CASP7 | orthology | Monodelphis |
| Casp7 | orthology | Mouse |
| CASP7 | orthology | Orangutan |
| CASP7 | orthology | Ornithorhynchus |
| CASP7 | orthology | Rabbit |
| Casp7 | orthology | Rat |
| CASP7 | orthology | Tetraodon |
| casp7 | orthology | Xenopus |
| T_guttata_ENSTGUP00000014729 | orthology | Zebra finch |
| T_guttata_ENSTGUP00000011206 | orthology | Zebra finch |
| casp7 | orthology | Zebrafish |
| NP_990057.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| CASP6_BOVIN | paralogy | Cow |
| IPI00704513.4 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP10 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP6 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP6 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP10 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP9 | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP6 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000005512 | paralogy | Monodelphis |
| Casp3 | paralogy | Mouse |
| Casp8 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Q5RB11_PONPY | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| CASP6 | paralogy | Rabbit |
| R_norvegicus_ENSRNOP00000040783 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp6 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| casp10 | paralogy | Xenopus |
| casp6 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| casp6l1 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| LOC798445 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006915 | apoptosis | biological_proccess | TAS |
| GO:0006508 | proteolysis | biological_proccess | IDA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0007507 | heart development | biological_proccess | IEA |
| GO:0001836 | release of cytochrome c from mitochondria | biological_proccess | IEA |
| GO:0009411 | response to UV | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005737 | cytoplasm | cell_component | TAS |
| GO:0005829 | cytosol | cell_component | EXP |
| GO:0031966 | mitochondrial membrane | cell_component | TAS |
| GO:0005789 | endoplasmic reticulum membrane | cell_component | TAS |
| GO:0005625 | soluble fraction | 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 [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1508
- Gene related info from GeneCards [?] : CASP7
- Ensembl genome browser [?] : ENSG00000165806
- Expression info from Arrayexpress [?] : ENSG00000165806
- Protein expression from Protein Atlas: [?] ENSG00000165806
- Community gene edition from Wikigenes: [?] 840
- OMIM gene information: 601761
- OMIM disease information:
Click on [?] for more information.
