GCN2 serine/threonine-protein kinase GCN2 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: GCN2
Gene description: serine/threonine-protein kinase GCN2
Primary source: FungiDB:YDR283C
Locus tag: YDR283C
See related: SGD:S000002691; AllianceGenome:SGD:S000002691; VEuPathDB:YDR283C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: AAS1; AAS102; NDR2
Summary: Enables eukaryotic translation initiation factor 2alpha kinase activity and tRNA binding activity. Involved in several processes, including negative regulation of TORC1 signaling; positive regulation of cellular response to amino acid starvation; and protein phosphorylation. Located in cytosolic ribosome. Human ortholog(s) of this gene implicated in pulmonary venoocclusive disease. Orthologous to human EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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See GCN2 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (1025070..1030049, complement)

Chromosome IV - NC_001136.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential requirements for P stalk components in activating yeast protein kinase Gcn2 by stalled ribosomes during stress.
Title: Differential requirements for P stalk components in activating yeast protein kinase Gcn2 by stalled ribosomes during stress.
A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation.
Title: A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation.
Origin of translational control by eIF2alpha phosphorylation: insights from genome-wide translational profiling studies in fission yeast.
Title: Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast.
Asp56 in actin is critical for the full activity of the amino acid starvation-responsive kinase Gcn2.
Title: Asp56 in actin is critical for the full activity of the amino acid starvation-responsive kinase Gcn2.
Global phosphoproteomics pinpoints uncharted Gcn2-mediated mechanisms of translational control.
Title: Global phosphoproteomics pinpoints uncharted Gcn2-mediated mechanisms of translational control.
Domain II of the translation elongation factor eEF1A is required for Gcn2 kinase inhibition.
Title: Domain II of the translation elongation factor eEF1A is required for Gcn2 kinase inhibition.
Global translational repression induced by iron deficiency in yeast depends on the Gcn2/eIF2alpha pathway.
Title: Global translational repression induced by iron deficiency in yeast depends on the Gcn2/eIF2α pathway.
ln4p depletion reduces this sequestration capacity, allowing uncharged tRNAGln to interact with Gcn2 kinase. The study sheds new light on mutant aaRS disease aetiologies, and explains how aaRS sequestration of uncharged tRNAs can prevent GCN4 activation under non-starvation conditions.
Title: The molecular aetiology of tRNA synthetase depletion: induction of a GCN4 amino acid starvation response despite homeostatic maintenance of charged tRNA levels.
Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2alpha, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator
Title: Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan.
findings demonstrate that TORC1 is an effector of Gcn2 in amino acid signaling, hence defining a novel mechanism by which TORC1 senses amino acid starvation
Title: General Control Nonderepressible 2 (GCN2) Kinase Inhibits Target of Rapamycin Complex 1 in Response to Amino Acid Starvation in Saccharomyces cerevisiae.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables tRNA binding	IDA Inferred from Direct Assay more info	PubMed
enables tRNA binding	IEA Inferred from Electronic Annotation more info
enables tRNA binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
involved_in DNA damage checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in GCN2-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cytoplasmic translational initiation in response to stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cellular response to amino acid starvation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cellular response to amino acid starvation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in post-transcriptional regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in regulation of translational initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of translational initiation by eIF2 alpha phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in translation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosolic ribosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytosolic ribosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: serine/threonine-protein kinase GCN2

NP_010569.3

EC 2.7.11.1

Protein kinase; phosphorylates the alpha-subunit of translation initiation factor eIF2 (Sui2p) in response to starvation; activated by uncharged tRNAs and the Gcn1p-Gcn20p complex; contributes to DNA damage checkpoint control

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001136.10 Reference assembly

Range

1025070..1030049 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001180591.3 → NP_010569.3 TPA: serine/threonine-protein kinase GCN2 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_010569.3

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VSR3, P15442

UniProtKB/TrEMBL

A0A8H8UNI5, A6ZYN2, B5VGG1, N1P8J5

Conserved Domains (5) summary

smart00591
Location:18 → 128

RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain

COG0124
Location:1015 → 1485

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

cd14012
Location:273 → 526

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:593 → 979

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

pfam12745
Location:1387 → 1657

HGTP_anticodon2; Anticodon binding domain of tRNAs