Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-aspartate + L-glutamine + H2O | Homo sapiens | - |
AMP + diphosphate + L-asparagine + L-glutamate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
adrenal cortex | - |
Homo sapiens | - |
astrocytoma cell | - |
Homo sapiens | - |
glioma cell | - |
Homo sapiens | - |
additional information | ASNS expression is not detected in normal brain tissue, and the expression is marginal in low-grade pilocytic astrocytoma and diffuse astrocytoma | Homo sapiens | - |
neuroblastoma cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-aspartate + L-glutamine + H2O | - |
Homo sapiens | AMP + diphosphate + L-asparagine + L-glutamate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ASNS | - |
Homo sapiens |
Asparagine synthetase | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | transcription factor ATF4 induces asparagine synthetase which results in glutamine-dependent asparagine synthesis from aspartate, in turn asparagine accumulation then suppresses GCN2 and reduces ATF4 | up |
General Information | Comment | Organism |
---|---|---|
malfunction | knockdown of asparagine synthetase (ASNS) leads to cell death even in the presence of glutamine, which can be reversed by addition of exogenous asparagine. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. ASNS knockdown leads to profound apoptosis even in the presence of glutamine. Addition of extracellular asparagine completely restored cell survival and proliferation. Clinically, the expression of ASNS correlates with the progression of disease and poor prognosis of glioma and neuroblastoma patients. In neuroblastoma with unfavourable prognosis, ASNS expression is significantly higher. Asparagine-induced suppression of apoptosis: asparagine addition to glutamine-deprived cells alters the transcriptional response, suppressing the induction of the reported UPR effectors CHOP and XBP1 while maintaining the transcriptional induction of adaptive components of the UPR-response such as ASNS and HERPUD1. At the protein level, exogenous addition of asparagine suppresses CHOP induction without altering ATF4 accumulation or upstream eIF2alpha phosphorylation | Homo sapiens |
physiological function | asparagine synthetase (ASNS) plays an important role during tumor cell accumulation and progression by maintaining cell viability. The enzyme synthesizes asparagine de novo from aspartate and glutamine. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. The anti-apoptotic function of glutamine depends on the ability of asparagine synthetase to maintain glutamine-dependent biosynthesis of asparagine. Transcription factor ATF4 induces asparagine synthetase which results in glutamine-dependent asparagine synthesis from aspartate, in turn asparagine accumulation then suppresses GCN2 and reduces ATF4 | Homo sapiens |