CASP12 (Homo sapiens)
Description [+]
- Synonyms: CASP12,
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Inactive caspase-12 (CASP-12) [Source:UniProtKB/Swiss-Prot;Acc:Q6UXS9]
- Family: CASPASE
- Process: immunity,
- Pathways: inflammasome,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp12
- WIKI: CASP12-H_sapiens
References [+]
- Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.
- Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J
- Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too little apoptosis can also cause disease. The family of cysteine proteases, the so- called caspases, are critical mediators of programmed cell death, and thus far 14 family members have been identified. Some of these, such as caspase-8, mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9, mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis. Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12 are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli. Furthermore, we show that caspase-12-deficient cortical neurons are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity. Nature. 2000 Jan 6;403(6765):98-103.
- References from Mouse ortholog(s):
- Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice.
- Saleh M, Mathison JC, Wolinski MK, Bensinger SJ, Fitzgerald P, Droin N, Ulevitch RJ, Green DR, Nicholson DW
- Caspases function in both apoptosis and inflammatory cytokine processing and thereby have a role in resistance to sepsis. Here we describe a novel role for a caspase in dampening responses to bacterial infection. We show that in mice, gene-targeted deletion of caspase-12 renders animals resistant to peritonitis and septic shock. The resulting survival advantage was conferred by the ability of the caspase-12-deficient mice to clear bacterial infection more efficiently than wild-type littermates. Caspase-12 dampened the production of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-18 (interferon (IFN)-gamma inducing factor) and IFN-gamma, but not tumour-necrosis factor-alpha and IL-6, in response to various bacterial components that stimulate Toll-like receptor and NOD pathways. The IFN-gamma pathway was crucial in mediating survival of septic caspase-12-deficient mice, because administration of neutralizing antibodies to IFN-gamma receptors ablated the survival advantage that otherwise occurred in these animals. Mechanistically, caspase-12 associated with caspase-1 and inhibited its activity. Notably, the protease function of caspase-12 was not necessary for this effect, as the catalytically inactive caspase-12 mutant Cys299Ala also inhibited caspase-1 and IL-1beta production to the same extent as wild-type caspase-12. In this regard, caspase-12 seems to be the cFLIP counterpart for regulating the inflammatory branch of the caspase cascade. In mice, caspase-12 deficiency confers resistance to sepsis and its presence exerts a dominant-negative suppressive effect on caspase-1, resulting in enhanced vulnerability to bacterial infection and septic mortality. Nature. 2006 Apr 20;440(7087):1064-8.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | CARD | 4 | 91 |
| PFAM A | Peptidase_C14 | 104 | 337 |
Protein sequence [+]
CASP12 | Homo sapiens | 9606 | length:341
MADEKPSNGVLVHMVKLLIKTFLDGIFDDLMENNVLNTDEIHLIGKCLKFVVSNAENLVD
DITETAQTAGKIFREHLWNSKKQLSSDISSDGEREANMPGLNIRNKEFNYLHNRNGSELD
LLGMRDLLENLGYSVVIKENLTAQEMETALRQFAAHPEHQSSDSTFLVFMSHSILNGICG
TKHWDQEPDVLHDDTIFEIFNNRNCQSLKDKPKVIIMQACRGNGAGIVWFTTDSGKAGAD
THGRLLQGNICNDAVTKAHVEKDFIAFKSSTPHNVSWRHETNGSVFISQIIYYFREYSWS
HHLEEIFQKVQHSFETPNILTQLPTIERLSMTRYFYLFPGN
DITETAQTAGKIFREHLWNSKKQLSSDISSDGEREANMPGLNIRNKEFNYLHNRNGSELD
LLGMRDLLENLGYSVVIKENLTAQEMETALRQFAAHPEHQSSDSTFLVFMSHSILNGICG
TKHWDQEPDVLHDDTIFEIFNNRNCQSLKDKPKVIIMQACRGNGAGIVWFTTDSGKAGAD
THGRLLQGNICNDAVTKAHVEKDFIAFKSSTPHNVSWRHETNGSVFISQIIYYFREYSWS
HHLEEIFQKVQHSFETPNILTQLPTIERLSMTRYFYLFPGN
Structure links:
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS01122
- Profile motif and domain profile information: PS50209
- Profile motif and domain profile information: PS50207
- Profile motif and domain profile information: PS50208
- Interpro domain information: Q6UXS9
- PFAM domain and domain family information: Q6UXS9
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_990255.1 | orthology | Chicken |
| CASP12 | orthology | Chimpanzee |
| CASP12 | orthology | Dog |
| T_rubripes_ENSTRUP00000035020 | orthology | Fugu |
| T_rubripes_ENSTRUP00000019853 | orthology | Fugu |
| T_rubripes_ENSTRUP00000013027 | orthology | Fugu |
| CASP12 | orthology | Gasterosteus |
| CASP12 | orthology | Gorilla |
| CASP12 | orthology | Horse |
| A_carolinensis_ENSACAP00000013361 | orthology | Lyzard |
| CASP12 | orthology | Macaca |
| CASP12 | orthology | Medaka |
| Casp12 | orthology | Mouse |
| CASP12 | orthology | Orangutan |
| Casp12 | orthology | Rat |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| LOC566185 | orthology | Zebrafish |
| caspa | orthology | Zebrafish |
| caspb | orthology | Zebrafish |
| CASPS6 | paralogy | Anopheles |
| CASPS1 | paralogy | Anopheles |
| NP_990056.1 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| CASP4 | paralogy | Chimpanzee |
| CASP1 | paralogy | Chimpanzee |
| XR_019722.1 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP2 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| IPI00688117.2 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| NP_001029681.1 | paralogy | Cow |
| IPI00707783.1 | paralogy | Cow |
| IPI00704513.4 | paralogy | Cow |
| A0PCH9_BOVIN | paralogy | Cow |
| CASPD_BOVIN | paralogy | Cow |
| CASP3_CANFA | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP2 | paralogy | Dog |
| C_familiaris_ENSCAFP00000007585 | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP1_CANFA | paralogy | Dog |
| CASP14 | paralogy | Dog |
| CASP2 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP2 | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| CASP5 | paralogy | Gorilla |
| CASP7 | paralogy | Horse |
| CASP4 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP1_HORSE | paralogy | Horse |
| CASP14 | paralogy | Horse |
| CASP2 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP4 | paralogy | Human |
| CASP2 | paralogy | Human |
| Caspase-14 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP1 | paralogy | Human |
| CASP5 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Lyzard |
| CASP14 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP14 | paralogy | Macaca |
| CASP1 | paralogy | Macaca |
| CASP5 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP4 | paralogy | Macaca |
| Q8SPP8_MACMU | paralogy | Macaca |
| CASP2 | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| M_domestica_ENSMODP00000034022 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034020 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP14 | paralogy | Monodelphis |
| CASP2 | paralogy | Monodelphis |
| NP_001035238.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034033 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| Casp9 | paralogy | Mouse |
| Casp1 | paralogy | Mouse |
| Casp2 | paralogy | Mouse |
| Caspase-14 | paralogy | Mouse |
| Casp4 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| CASP2 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP4 | paralogy | Orangutan |
| CASP5 | paralogy | Orangutan |
| CASP1 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP2 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000016591 | paralogy | Ornithorhynchus |
| CASP14 | paralogy | Rabbit |
| CASP1 | paralogy | Rabbit |
| CASP4 | paralogy | Rabbit |
| CASP2 | paralogy | Rabbit |
| Casp14_predicted | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp4 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp1 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| Casp2 | paralogy | Rat |
| CASP2 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| CASP2 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| LOC563034 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
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Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :19004
- Gene related info from GeneCards [?] : CASP12
- Ensembl genome browser [?] : ENSG00000204403
- Expression info from Arrayexpress [?] : ENSG00000204403
- Protein expression from Protein Atlas: [?] ENSG00000204403
- OMIM gene information: 608633
- OMIM disease information:
- refseq_dna: NR_000035
Click on [?] for more information.
