3.4.22.B26: calpain 6
This is an abbreviated version!
For detailed information about calpain 6, go to the full flat file.
Word Map on EC 3.4.22.B26
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3.4.22.B26
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non-proteolytic
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medicine
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myometrium
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leiomyomas
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nonlysosomal
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pinocytotic
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calpastatin
- 3.4.22.B26
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non-proteolytic
- medicine
-
myometrium
- leiomyomas
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nonlysosomal
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pinocytotic
- calpastatin
Reaction
A microtubule-stabilizing protein. The enzyme lacks the active-site catalytic cysteine residue and proteolytic activity has not been detected. =
Synonyms
calpain 6, calpain-6, CAPN6
ECTree
3.4.22.B26 calpain 6Advanced search results
results (
results (| Results | in table |
|---|---|
| 2 | AA Sequence |
| 4 | Application |
| 141 | Disease/ Diagnostics |
| 4 | Expression |
| 9 | General Information |
| 2 | Inhibitors |
| 6 | Organism |
| 1 | Reaction |
| 6 | Reference |
| 18 | Source Tissue |
| 4 | Synonyms |
General Information
General Information on EC 3.4.22.B26 - calpain 6
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
malfunction
metabolism
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the enzyme capain-6 is negatively controlled by the proteoglycan syndecan-2, that controls the activity of various cytokines and growth factors and also modulates apoptosis and response to cytotoxic agents in osteosarcoma cell lines. Syndecan-2 exerts its pro-apoptotic function through modulation of the endothelin-1/NFkappaB signaling and through downregulation of calpain-6. Calpain-6 expression in osteosarcoma cells depends on endothelin-1, a mediator of the tumor progression in bone. Syndecan-2 overexpression alters ERK1/2, PI3K/AKT and NFjB pathways that are calpain-6-promoting signals downstream of endothelin-1
physiological function
malfunction
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inhibition of calpain-6 with shRNA results in decreased proliferation, increased spontaneous apoptosis and increased sensitivity to doxorubicin and also methotrexate in responsive and resistant osteosarcoma cells
malfunction
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knockdown of calpain-6 in NIH-3T3 cells results in Rac1 activation, which promotes cell migration, spreading and lamellipodial protrusion. Upon knockdown of calpain-6, GEF-H1 translocates from microtubules to the lamellipodial region and to interact with Rac1. RhoA activity is decreased upon knockdown of calpain-6
physiological function
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calpain-6 is a microtubule-stabilizing protein that regulates Rac1 activity and cell motility through interaction with the Rho guanine-nucleotide-exchange factor GEF-H1. Calpain-6 is involved in the regulation of the organization of cortical actin and subsequent changes in cell motility and morphology, independent of the proteolytic activity of calpains
physiological function
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calpain-6 is an endothelin-1 signaling dependent protective factor in chemoresistant osteosarcoma
physiological function
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calpain-6 is a protective factor that contributes to abnormal cell survival
physiological function
calpain-6 expression is associated with cancer stem cell features. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. Calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux
physiological function
calpain-6 expression is associated with cancer stem cell features. In mouse models of bone sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic capacities. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. Calpain-6 knockdown blocks tumor development in mouse and induces depletion of the cancer stem cell population. Calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux
physiological function
inflammatory cytokines induce nonproteolytic calpain-6 (CAPN6), which associates with the essential exon junction complex-loading factor CWC22 in the cytoplasm. This association disturbs the nuclear localization of CWC22, thereby suppressing the splicing of target genes, including those related to Rac1 signaling. CAPN6 deficiency in low density lipoprotein receptor-deficient mice restores CWC22/EJC/Rac1 signaling, reduces pinocytotic deposition of native low density lipoprotein in macrophages, and attenuates macrophage recruitment into the lesions, generating an atheroprotective phenotype in the aorta. In macrophages, the induction of CAPN6 in the atheroma interior limits macrophage movements, resulting in a decline in cell clearance from the lesions. Myeloid CAPN6 contributes to atherogenesis in a murine model of bone marrow transplantation
