Literature summary for 6.3.5.4 extracted from

Zhang, J.; Fan, J.; Venneti, S.; Cross, J.R.; Takagi, T.; Bhinder, B.; Djaballah, H.; Kanai, M.; Cheng, E.H.; Judkins, A.R.; Pawel, B.; Baggs, J.; Cherry, S.; Rabinowitz, J.D.; Thompson, C.B.
Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion (2014), Mol. Cell, 56, 205-218 .

Search for more literature for 6.3.5.4

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

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 and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + L-aspartate + L-glutamine + H2O	-	Homo sapiens	AMP + diphosphate + L-asparagine + L-glutamate	-	?

Synonyms

Synonyms	Comment	Organism
ASNS	-	Homo sapiens
Asparagine synthetase	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

Expression

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

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

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)