Protein: eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) (D4A7V9)
Organism: Rattus norvegicus (Rat)
Function: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (By similarity). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (By similarity). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a role in feeding behavior to maintain amino acid homeostasis; contributes to the innate aversion toward diets of imbalanced amino acid composition. Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9QZ05}.
Interaction partners:
- Eukaryotic translation initiation factor 2 subunit 1
- Nuclear factor erythroid 2-related factor 2
- Stalled ribosome sensor GCN1
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Interferon-induced protein with tetratricopeptide repeats 1
- Interferon-induced protein with tetratricopeptide repeats 1B-like
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
- NF-kappa-B essential modulator
- Cyclic AMP-dependent transcription factor ATF-4
- Aspartate--tRNA ligase, mitochondrial
Sequence:
MAGGRGAAGRGPAEPQESYSQRQDHELQALEAIYGSDFQDLRPDARGRVREPPEINLVLYPQGLAGEEVYVQVELRVKCPPTYPDVVPEIELKNTKGLSNESVNLLKSHLEELAKKQCGEVMIFELAHHVQSFLSEHNKPPPKSFHEEMLERQAQEKQQRLLEARQKEEQEQREILHEIQKRKEEIKEEKKRKEMAKQERLEITSLTNQDHASKRDPAGHRAAAFLHGGSPDFVGNGKARAHSSGRSRRERQYSVCSGEASPGSCDILYFCVGSADQLMVHKGKCVGSDEQLGKVVYNALETATGSFVLLYEWVLQWQKKMGPCLTSQEKEKIDKCKKQIQGAETEFSSLVKLSHPNIVRYFAMNSREEKDSIVVDILAEHISGISLAAHLSHSGPVPMHQLRKYTAQLLAGLDYLHRNSVVHKVLSTASVLVDAEGTVKITDYSISKRLADICKEDVFEQTRVRFSDSALPYKTGKKGDVWRLGLLLLSLSQGQECEEYPVTIPSDLPADFQDFLKKCVCLDDKERWSPQQLLKHSFINPQPKMPLVEQSPEDSGGQDYIETIIPSNQLPSAAFFTETQRQFSRYFIEFEELQLLGKGAFGAVIKVQNKLDGCCYAVKRIPINPASRQFRRIKGEVTLLSRLHHENIVRYYNAWIERHERPAVPGTPPPDYIPQAQNSSATGGKASGDTEELGSVEAAAPPPILSSSVEWSTSAERSNSARFPVTGQDSSSDEEDEDERDGVFSQSFLPASDSDSDIIFDNEDENSKSQNQDEDCNEKDSRHEIEPSVTTEAVHYLYIQMEYCEKSTLRDTIDQGLFRDTSRLWRLFREILDGLAYIHEKGMIHRDLKPVNIFLDSDDHVKIGDFGLATDHLAFNAEGKQDDQAGDHVIKSDPSGHLTGMVGTALYVSPEVQGSTKSAYNQKVDLFSLGIILFEMSYHPMVTASERIFVLNQLRDPTSPKFPDDFEDGEHTKQKSVISWLLNHDPAKRPTAMELLKSELLPPPQMEESELHEVLHHTLANTDGKAYRTMMSQLFCQHSSPAIDYTYDSDILKGNFLIRTAKIQQLVCETIVRVFKRHGAVQLCTPLLLPRNRQIYEHNEAALFMDHSGMLVMLPFDLRVPFARYVARNNILNLKRYCIERVFRPRKLDRFHPKELLECAFDIVTSTANSSLPTAETIYTIYEVIQEFPALQERNYSIYLNHTMLLKAILLHCGIPEDKLSQVYVILYDAVTEKLTRREVEAKFCNLSLSSNSLCRLYKFIEQKGDLQDLTPTINSLIKQKTGIAQLVKYSLKDLEEVVGLLKKLGVKLQVSINLGLVYKVQQHNGIIFQFLAFSKRRQRVVPEILAAGGRYDLLIPKFRGPQALGPVPTAVGVSIAIDKIFAAVLNMGEPVTVSSCDLLVVSAGQMSMSRAINLTQKLWTAGITAEIMYDWSQSQEELQEYCRHHEITYVALVSDKEGSHVKVKSFEKERQTEKRVLESDLVDHVMQKLRTKVGDERNFRDASDNLAVQTLKGSFSNASGLFEIHGTTVVPTVSVISPEKLSASTRRRHEIQVQTRLQTTLANLHQKSSEIEILAVDLPKETILQFLSLEWDADEQAFNTTVKQLLSRLPKQRYLKLVCDEIYNIKVEKKVSVLFLYSYRDDYYRILF