Protein: eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (General control non-derepressible protein 2) (Serine/threonine-protein kinase GCN2) (P15442)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
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. Plays a role as an activator of the general amino acid control (GAAC) pathway required for adapatation to nutrient starvation. 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. Binds uncharged tRNAs.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:2038314}.
Sequence: MSLSHLTLDQYYEIQCNELEAIRSIYMDDFTDLTKRKSSWDKQPQIIFEITLRSVDKEPVESSITLHFAMTPMYPYTAPEIEFKNVQNVMDSQLQMLKSEFKKIHNTSRGQEIIFEITSFTQEKLDEFQNVVNTQSLEDDRLQRIKETKEQLEKEEREKQQETIKKRSDEQRRIDEIVQRELEKRQDDDDDLLFNRTTQLDLQPPSEWVASGEAIVFSKTIKAKLPNNSMFKFKAVVNPKPIKLTSDIFSFSKQFLVKPYIPPESPLADFLMSSEMMENFYYLLSEIELDNSYFNTSNGKKEIANLEKELETVLKAKHDNVNRLFGYTVERMGRNNATFVWKIRLLTEYCNYYPLGDLIQSVGFVNLATARIWMIRLLEGLEAIHKLGIVHKCINLETVILVKDADFGSTIPKLVHSTYGYTVLNMLSRYPNKNGSSVELSPSTWIAPELLKFNNAKPQRLTDIWQLGVLFIQIISGSDIVMNFETPQEFLDSTSMDETLYDLLSKMLNNDPKKRLGTLELLPMKFLRTNIDSTINRFNLVSESVNSNSLELTPGDTITVRGNGGRTLSQSSIRRRSFNVGSRFSSINPATRSRYASDFEEIAVLGQGAFGQVVKARNALDSRYYAIKKIRHTEEKLSTILSEVMLLASLNHQYVVRYYAAWLEEDSMDENVFESTDEESDLSESSSDFEENDLLDQSSIFKNRTNHDLDNSNWDFISGSGYPDIVFENSSRDDENEDLDHDTSSTSSSESQDDTDKESKSIQNVPRRRNFVKPMTAVKKKSTLFIQMEYCENRTLYDLIHSENLNQQRDEYWRLFRQILEALSYIHSQGIIHRDLKPMNIFIDESRNVKIGDFGLAKNVHRSLDILKLDSQNLPGSSDNLTSAIGTAMYVATEVLDGTGHYNEKIDMYSLGIIFFEMIYPFSTGMERVNILKKLRSVSIEFPPDFDDNKMKVEKKIIRLLIDHDPNKRPGARTLLNSGWLPVKHQDEVIKEALKSLSNPSSPWQQQVRESLFNQSYSLTNDILFDNSVPTSTPFANILRSQMTEEVVKIFRKHGGIENNAPPRIFPKAPIYGTQNVYEVLDKGGTVLQLQYDLTYPMARYLSKNPSLISKQYRMQHVYRPPDHSRSSLEPRKFGEIDFDIISKSSSESGFYDAESLKIIDEILTVFPVFEKTNTFFILNHADILESVFNFTNIDKAQRPLVSRMLSQVGFARSFKEVKNELKAQLNISSTALNDLELFDFRLDFEAAKKRLYKLMIDSPHLKKIEDSLSHISKVLSYLKPLEVARNVVISPLSNYNSAFYKGGIMFHAVYDDGSSRNMIAAGGRYDTLISFFARPSGKKSSNTRKAVGFNLAWETIFGIAQNYFKLASGNRIKKRNRFLKDTAVDWKPSRCDVLISSFSNSLLDTIGVTILNTLWKQNIKADMLRDCSSVDDVVTGAQQDGIDWILLIKQQAYPLTNHKRKYKPLKIKKLSTNVDIDLDLDEFLTLYQQETGNKSLINDSLTLGDKADEFKRWDENSSAGSSQEGDIDDVVAGSTNNQKVIYVPNMATRSKKANKREKWVYEDAARNSSNMILHNLSNAPIITVDALRDETLEIISITSLAQKEEWLRKVFGSGNNSTPRSFATSIYNNLSKEAHKGNRWAILYCHKTGKSSVIDLQR
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [299-1019]
- IPR006575: RWD domain (domain) [13-128]
- IPR050339: Cell Cycle and Stress Response Kinase (family) [583-1014]
- IPR036621: Anticodon-binding domain superfamily (homologous_superfamily) [1388-1493]
- IPR045864: Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL) (homologous_superfamily) [1029-1366]
- IPR041715: Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain (domain) [1038-1362]
- IPR016255: eIF-2-alpha kinase Gcn2 (family) [1-1659]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [831-843]
- IPR024435: Histidyl tRNA synthetase-related domain (domain) [1387-1657]
- IPR017441: Protein kinase, ATP binding site (binding_site) [605-629]
- IPR000719: Protein kinase domain (domain) [256-981]
- IPR016135: Ubiquitin-conjugating enzyme/RWD-like (homologous_superfamily) [1-138]
Interaction partners: - Eukaryotic translation initiation factor 2 subunit alpha
- eIF-2-alpha kinase activator GCN1
- Serine/threonine-protein kinase TOR1
- Translation initiation factor eIF2B subunit alpha
- General control transcription factor GCN4
- Protein GCN20
- Target of rapamycin complex 1 subunit KOG1
- Serine/threonine-protein kinase TOR2
- Eukaryotic translation initiation factor 2 subunit gamma
- Histidine biosynthesis trifunctional protein
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0045182 (translation regulator activity), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0009894 (regulation of catabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0019538 (protein metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:0006793 (phosphorus metabolic process), GO:0036211 (protein modification process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0034248 (regulation of amide metabolic process), GO:0043412 (macromolecule modification), GO:0034250 (positive regulation of amide metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0006446 (regulation of translational initiation), GO:0031326 (regulation of cellular biosynthetic process), GO:0051247 (positive regulation of protein metabolic process), GO:0010628 (positive regulation of gene expression), GO:0006796 (phosphate-containing compound metabolic process), GO:0031329 (regulation of cellular catabolic process), GO:0043555 (regulation of translation in response to stress), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:0006417 (regulation of translation), GO:0043558 (regulation of translational initiation in response to stress), GO:0006468 (protein phosphorylation), GO:0045727 (positive regulation of translation), GO:0016310 (phosphorylation), GO:0010608 (post-transcriptional regulation of gene expression)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)