Q9HGN1 · GCN2_SCHPO
- ProteineIF-2-alpha kinase GCN2
- Genegcn2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1576 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) on 'Ser-52' in response to low amino acid, carbon, or purine availability (PubMed:15611163, PubMed:15821139).
Required for adapatation to nutrient starvation by acting as a key component of the integrated stress response (ISR), by which cells alter their translational and transcriptional output in response to starvation (PubMed:15821139).
Converts phosphorylated eIF-2-alpha/SUI2 either to a competitive inhibitor of translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator GCN4, and hence allowing GCN4-mediated reprogramming of transcription to alleviate nutrient depletion (PubMed:15821139).
Binds uncharged tRNAs (By similarity).
Required for adapatation to nutrient starvation by acting as a key component of the integrated stress response (ISR), by which cells alter their translational and transcriptional output in response to starvation (PubMed:15821139).
Converts phosphorylated eIF-2-alpha/SUI2 either to a competitive inhibitor of translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator GCN4, and hence allowing GCN4-mediated reprogramming of transcription to alleviate nutrient depletion (PubMed:15821139).
Binds uncharged tRNAs (By similarity).
Catalytic activity
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
Activity regulation
The integrated stress response (ISR) is activated in response to conditions that promote ribosome collisions: gcn1, which acts as a ribosome collision sensor, activates gcn2. The RQC pathway and the integrated stress response (ISR) antagonize each other: hel2 prevents the activation of gcn2, while gcn2 suppresses RQC activation. Ribosome stalling-induced integrated stress response prefers ribosomes with empty A sites. The kinase activity is stimulated upon binding to uncharged tRNAs.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | eukaryotic translation initiation factor 2alpha kinase activity | |
Molecular Function | histone H2AS1 kinase activity | |
Molecular Function | protein serine kinase activity | |
Molecular Function | tRNA binding | |
Biological Process | cellular response to amino acid starvation | |
Biological Process | G1 to G0 transition | |
Biological Process | GCN2-mediated signaling | |
Biological Process | mitotic G1 DNA damage checkpoint signaling | |
Biological Process | negative regulation of cytoplasmic translational initiation | |
Biological Process | negative regulation of cytoplasmic translational initiation in response to stress | |
Biological Process | negative regulation of TORC1 signaling | |
Biological Process | positive regulation of autophagy | |
Biological Process | regulation of cytoplasmic translational initiation in response to stress |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameeIF-2-alpha kinase GCN2
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Taphrinomycotina > Schizosaccharomycetes > Schizosaccharomycetales > Schizosaccharomycetaceae > Schizosaccharomyces
Accessions
- Primary accessionQ9HGN1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000085962 | 1-1576 | eIF-2-alpha kinase GCN2 | |||
Sequence: MDAAKRLELCKEIQENEIEALKAIFMDDFEELKVRNAWNVTNGHVYCIHLCSRSANSKSIAKLDLCIELGRSYPYVKPVIKLQNGENVLNSQIRFLLDKLDTKAKDLLGEEMIFELASIVQDYLNDWQSDLSSQFASLEEERAVQLKHDRERAEVDLQLRLKREKDALFEEEQTLQNKIQDELQRRSYETPQSSSKKKTNSKETTSLETLPTSIYFDCSISVRDCHDSLVTFNRVLPLYTISHSNLSTLTLVKPESKEISLQDCVFLLRTVRISTPYWSTEDGKREIQELEYELESLKVIRHDLLASIYEYQLERETRGYGWRLYVLQEYSPKFTLFSLLQTVLTLDVETVRAFSNNILEGLAELHRLGISHKSLHLDNVVLFHSGHRTFAKLMDFGFTRTLRDMNASHPFNINSQSITNILPEGLYPPEVSESSFAAASRKTDIWCFGLLVLQMLCGAHVLNKFSSLKLIMTHVIPLLPGSYQDLVRRCLMRDSRKRPSAIDLLSSHVIRLGTAVLPPVEQGTFSKSARPSYGGQQDGIIDLLYRKSVSRYETDFEELEFLGRGGFGEVVKVKNRIDGRFYAVKKLVLLSDDKENSRILREVMTLSRLHHEHVVRYYTAWVETEANDTVTEIISSDSESLSQSLNMAVDFRQSSSLPADKLSSLDIHFEDDYNSSADEEDPEASDISFQYSNTSDKEGSSDKDSSIEEASSVKTQENGLNATLYIQMEYCEKLSLQDIIRDKIPVDEMWRLFRQILEALAYIHSRGMMHRDLKPGNIFLDENRNVKLGDFGLATENENYQDNNDKWKNRQSADEDLTTGVGTALYVAPELLSRRNGVRYDAKVDMYSLGIILFEMCMTFSTSMERIRIIDTIRSPSISFPSTFPFSRASHEFKVIHCLLQHDPTKRPSSQELLESEAIPPKVGEEFIQEGLRLLSNPNTPYYLKLLKVLFGQVPDRHKDFTYDFNLSEESGVLSKVSDRGWDSLLACLVRDHVVKVFRRHGAKERESHILFPKSSQYDKDQASVSLLDKNGTLLQLPYDTVLPYARNVARNAVEEEKTYLISDVFREAKGGGRPKAIKEISFDITTNSDNLDWYDAETIKALDEVLTEIPSLTESCILINHADILSSILDYLQVSKDKRRMATHILGQINQRLTLSQVRNQLRIESLVPSTTLDDLSLFDFRENYEEGASKLRKIFGKEMPQKMRTALNYMERVVKLLRALKISHQLYFMPLCVYNFEFYDGGLMFQAINLAEKSELICAGGRYDKLVRFFDPPLMRTARKKHVVGICFALEKLVFSMLRYIRFHNSKQSSKHSPSPTLKSVGPWAPRRVDVLVTSIGKDSILEKCSLLQELWALNIQADIVLRGASSLEEIVTHYRSEGINWVLVVRQKNTQMEHSVKARNILKNEDDEIRFDEVGMWLLGEINERKRNESMLQSKRILDSAQQDVAKFVDTSQSNLDVQLISLKDVNDRKYKWKHKQNAMNKVYDLVQSAIRESSEDAIALAVDCDSEAMEKLRSTTTLDEESWKRLIESCPASQREYMQRLQKKLVTLAEQDKKRVWICSFRTNEIYLYGLK |
Post-translational modification
Autophosphorylated.
Proteomic databases
PTM databases
Interaction
Subunit
Homodimer; homodimerization is important for kinase activation by uncharged tRNAs. Interacts (via N-terminal RWD domain) with gcn1 (via N- and C-terminus); this interaction stimulates gcn2 kinase activity in a gcn20-dependent manner in response to amino acid starvation. Interacts (via N-terminus) with the gcn1-gcn20 complex on translating ribosomes in amino acid-starved cells; gcn1 may bind near the ribosomal A-site and promotes the transfer of uncharged tRNAs from the A-site to the tRNA-binding domain in gcn2 for its subsequent kinase activation, and hence allowing fil1 translational activation and derepression of amino acid biosynthetic genes.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 16-127 | RWD | ||||
Sequence: NEIEALKAIFMDDFEELKVRNAWNVTNGHVYCIHLCSRSANSKSIAKLDLCIELGRSYPYVKPVIKLQNGENVLNSQIRFLLDKLDTKAKDLLGEEMIFELASIVQDYLNDW | ||||||
Region | 180-204 | Disordered | ||||
Sequence: QDELQRRSYETPQSSSKKKTNSKET | ||||||
Compositional bias | 186-204 | Polar residues | ||||
Sequence: RSYETPQSSSKKKTNSKET | ||||||
Domain | 235-511 | Protein kinase 1 | ||||
Sequence: VLPLYTISHSNLSTLTLVKPESKEISLQDCVFLLRTVRISTPYWSTEDGKREIQELEYELESLKVIRHDLLASIYEYQLERETRGYGWRLYVLQEYSPKFTLFSLLQTVLTLDVETVRAFSNNILEGLAELHRLGISHKSLHLDNVVLFHSGHRTFAKLMDFGFTRTLRDMNASHPFNINSQSITNILPEGLYPPEVSESSFAAASRKTDIWCFGLLVLQMLCGAHVLNKFSSLKLIMTHVIPLLPGSYQDLVRRCLMRDSRKRPSAIDLLSSHVIR | ||||||
Domain | 556-928 | Protein kinase 2 | ||||
Sequence: FEELEFLGRGGFGEVVKVKNRIDGRFYAVKKLVLLSDDKENSRILREVMTLSRLHHEHVVRYYTAWVETEANDTVTEIISSDSESLSQSLNMAVDFRQSSSLPADKLSSLDIHFEDDYNSSADEEDPEASDISFQYSNTSDKEGSSDKDSSIEEASSVKTQENGLNATLYIQMEYCEKLSLQDIIRDKIPVDEMWRLFRQILEALAYIHSRGMMHRDLKPGNIFLDENRNVKLGDFGLATENENYQDNNDKWKNRQSADEDLTTGVGTALYVAPELLSRRNGVRYDAKVDMYSLGIILFEMCMTFSTSMERIRIIDTIRSPSISFPSTFPFSRASHEFKVIHCLLQHDPTKRPSSQELLESEAIPPKVGEEFI | ||||||
Region | 673-714 | Disordered | ||||
Sequence: YNSSADEEDPEASDISFQYSNTSDKEGSSDKDSSIEEASSVK |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,576
- Mass (Da)181,193
- Last updated2004-04-13 v2
- Checksum97A97E1025C37087
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 186-204 | Polar residues | ||||
Sequence: RSYETPQSSSKKKTNSKET |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY705913 EMBL· GenBank· DDBJ | AAU11313.1 EMBL· GenBank· DDBJ | mRNA | ||
CU329671 EMBL· GenBank· DDBJ | CAC05730.2 EMBL· GenBank· DDBJ | Genomic DNA |