Q9HGN1 · GCN2_SCHPO

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).

Catalytic activity

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.

TypeIDPosition(s)Description
Binding site562-570ATP (UniProtKB | ChEBI)
Binding site585ATP (UniProtKB | ChEBI)
Active site772Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functioneukaryotic translation initiation factor 2alpha kinase activity
Molecular Functionhistone H2AS1 kinase activity
Molecular Functionprotein serine kinase activity
Molecular FunctiontRNA binding
Biological Processcellular response to amino acid starvation
Biological ProcessG1 to G0 transition
Biological ProcessGCN2-mediated signaling
Biological Processmitotic G1 DNA damage checkpoint signaling
Biological Processnegative regulation of cytoplasmic translational initiation
Biological Processnegative regulation of cytoplasmic translational initiation in response to stress
Biological Processnegative regulation of TORC1 signaling
Biological Processpositive regulation of autophagy
Biological Processregulation of cytoplasmic translational initiation in response to stress

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    eIF-2-alpha kinase GCN2
  • Alternative names
    • Serine/threonine-protein kinase gcn2
      (EC:2.7.11.1
      ) . EC:2.7.11.1 (UniProtKB | ENZYME | Rhea)
    • Serine/threonine-protein kinase ppk28

Gene names

    • Name
      gcn2
    • Synonyms
      ppk28
    • ORF names
      SPBC36B7.09, SPBP18G5.01

Organism names

Accessions

  • Primary accession
    Q9HGN1
  • Secondary accessions
    • Q66T01
    • Q9HDW2

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Decreases translation of transcription factor fil1 (PubMed:29432178).
Decreases RNA level and translation of genes involved the response to amino acid starvation (PubMed:29432178).

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000859621-1576eIF-2-alpha kinase GCN2

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.

TypeIDPosition(s)Description
Domain16-127RWD
Region180-204Disordered
Compositional bias186-204Polar residues
Domain235-511Protein kinase 1
Domain556-928Protein kinase 2
Region673-714Disordered

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,576
  • Mass (Da)
    181,193
  • Last updated
    2004-04-13 v2
  • Checksum
    97A97E1025C37087
MDAAKRLELCKEIQENEIEALKAIFMDDFEELKVRNAWNVTNGHVYCIHLCSRSANSKSIAKLDLCIELGRSYPYVKPVIKLQNGENVLNSQIRFLLDKLDTKAKDLLGEEMIFELASIVQDYLNDWQSDLSSQFASLEEERAVQLKHDRERAEVDLQLRLKREKDALFEEEQTLQNKIQDELQRRSYETPQSSSKKKTNSKETTSLETLPTSIYFDCSISVRDCHDSLVTFNRVLPLYTISHSNLSTLTLVKPESKEISLQDCVFLLRTVRISTPYWSTEDGKREIQELEYELESLKVIRHDLLASIYEYQLERETRGYGWRLYVLQEYSPKFTLFSLLQTVLTLDVETVRAFSNNILEGLAELHRLGISHKSLHLDNVVLFHSGHRTFAKLMDFGFTRTLRDMNASHPFNINSQSITNILPEGLYPPEVSESSFAAASRKTDIWCFGLLVLQMLCGAHVLNKFSSLKLIMTHVIPLLPGSYQDLVRRCLMRDSRKRPSAIDLLSSHVIRLGTAVLPPVEQGTFSKSARPSYGGQQDGIIDLLYRKSVSRYETDFEELEFLGRGGFGEVVKVKNRIDGRFYAVKKLVLLSDDKENSRILREVMTLSRLHHEHVVRYYTAWVETEANDTVTEIISSDSESLSQSLNMAVDFRQSSSLPADKLSSLDIHFEDDYNSSADEEDPEASDISFQYSNTSDKEGSSDKDSSIEEASSVKTQENGLNATLYIQMEYCEKLSLQDIIRDKIPVDEMWRLFRQILEALAYIHSRGMMHRDLKPGNIFLDENRNVKLGDFGLATENENYQDNNDKWKNRQSADEDLTTGVGTALYVAPELLSRRNGVRYDAKVDMYSLGIILFEMCMTFSTSMERIRIIDTIRSPSISFPSTFPFSRASHEFKVIHCLLQHDPTKRPSSQELLESEAIPPKVGEEFIQEGLRLLSNPNTPYYLKLLKVLFGQVPDRHKDFTYDFNLSEESGVLSKVSDRGWDSLLACLVRDHVVKVFRRHGAKERESHILFPKSSQYDKDQASVSLLDKNGTLLQLPYDTVLPYARNVARNAVEEEKTYLISDVFREAKGGGRPKAIKEISFDITTNSDNLDWYDAETIKALDEVLTEIPSLTESCILINHADILSSILDYLQVSKDKRRMATHILGQINQRLTLSQVRNQLRIESLVPSTTLDDLSLFDFRENYEEGASKLRKIFGKEMPQKMRTALNYMERVVKLLRALKISHQLYFMPLCVYNFEFYDGGLMFQAINLAEKSELICAGGRYDKLVRFFDPPLMRTARKKHVVGICFALEKLVFSMLRYIRFHNSKQSSKHSPSPTLKSVGPWAPRRVDVLVTSIGKDSILEKCSLLQELWALNIQADIVLRGASSLEEIVTHYRSEGINWVLVVRQKNTQMEHSVKARNILKNEDDEIRFDEVGMWLLGEINERKRNESMLQSKRILDSAQQDVAKFVDTSQSNLDVQLISLKDVNDRKYKWKHKQNAMNKVYDLVQSAIRESSEDAIALAVDCDSEAMEKLRSTTTLDEESWKRLIESCPASQREYMQRLQKKLVTLAEQDKKRVWICSFRTNEIYLYGLK

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias186-204Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY705913
EMBL· GenBank· DDBJ
AAU11313.1
EMBL· GenBank· DDBJ
mRNA
CU329671
EMBL· GenBank· DDBJ
CAC05730.2
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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