Protein: Stalled ribosome sensor GCN1 (GCN1 eIF-2-alpha kinase activator homolog) (GCN1-like protein 1) (General control of amino-acid synthesis 1-like protein 1) (Translational activator GCN1) (E9PVA8)
Organism: Mus musculus (Mouse)
Function: Acts as a positive activator of the GCN2 protein kinase activity in response to amino acid starvation. Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during this process, GCN1 seems to act as a chaperone to facilitate delivery of uncharged tRNAs that enter the A site of ribosomes to the tRNA-binding domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase activity (By similarity). Participates in the repression of global protein synthesis and in gene-specific mRNA translation activation, such as the transcriptional activator ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:32324833, ECO:0000305|PubMed:23447528}. Note=Associates with ribosomes in undifferentiated neuroblastoma cells and increases after neuronal differentiation (PubMed:23447528). {ECO:0000269|PubMed:23447528}.
Interaction partners:
- ATP-binding cassette sub-family F member 3
- ATP-binding cassette sub-family F member 1
- eIF-2-alpha kinase GCN2
- Large ribosomal subunit protein eL19
- Developmentally-regulated GTP-binding protein 2
- Small ribosomal subunit protein uS15
- Small ribosomal subunit protein uS19
- Small ribosomal subunit protein uS5
- Small ribosomal subunit protein uS4
- Small ribosomal subunit protein uS3
Sequence:
MAADTQVSETLKRFAVKVTTASVKERREILSELGRCIAGKDLPEGAVKGLCKLFCLTLHRYRDAASRRALQAAIQQLAEAQPEATAKNLLHSLQSSGVGSKACVPSKSSGSAALLALTWTCLLVRIVFPLKAKRQGDIWNKLVEVQCLLLLEVLGGSHKHAVDGAVKKLTKLWKENPGLVEQYFSAILSLEPSQNYAAMLGLLVQFCTNHKEMDAVSQHKSTLLEFYVKNILMSKAKPPKYLLDNCAPLLRFMSHSEFKDLILPTIQKSLLRSPENVIETISSLLASVTLDLSQYALDIVKGLANQLKSNSPRLMDEAVLALRNLARQCSDSSATEALTKHLFAILGGSEGKLTIIAQKMSVLSGIGSLSHHVVSGPSGQVLNGCVAELFIPFLQQEVHEGTLVHAVSILALWCNRFTTEVPKKLTDWFKKVFSLKTSTSAVRHAYLQCMLASFRGDTLLQALDFLPLLMQTVEKAASQGTQVPTVTEGVAAALLLSKLSVADAQAEAKLSGFWQLVVDEKRQTFTSEKFLLLASEDALCTVLRLTERLFLDHPHRLTNSKVQQYYRVLVAVLLSRTWHVRRQAQQTVRKLLSSLGGVKLANGLLDELKTVLNSHKVLPLEALVTDAGEVTEMGKTYVPPRVLQEALCVISGVPGLKGDIPSTEQLAQEMLIISHHPSLVAVQSGLWPALLTRMKIDPDAFITRHLDQIIPRITTQSPLNQSSMNAMGSLSVLSPDRVLPQLISTITASVQNPALCLVTREEFSIMQTPAGELFDKSIIQSAQQDSIKKANMKRENKAYSFKEQIIEMELKEEIKKKKGIKEEVQLTSKQKEMLQAQMDKEAQIRRRLQELDGELEAALGLLDAIMARNPCGLIQYIPVLVDAFLPLLKSPLAAPRVKGPFLSLAACVMPPRLKTLGTLVSHVTLRLLKPECALDKSWCQEELPVAVRRAVSLLHTHTIPSRVGKGEPDAAPLSAPAFSLVFPMLKMVLTEMPYHSEEEEEQMAQILQILTVHAQLRASPDTPPERVDENGPELLPRVAMLRLLTWVIGTGSPRLQVLASDTLTALCASSSGEDGCAFAEQEEVDVLLAALQSPCASVRETALRGLMELRLVLPSPDTDEKSGLSLLRRLWVIKFDKEDEIRKLAERLWSTMGLDLQSDLCSLLIDDVIYHEAAVRQAGAEALSQAVARYQRQAAEVMGRLMEIYQEKLYRPPPVLDALGRVISESPPDQWEARCGLALALNKLSQYLDSSQVKPLFQFFVPDALNDRNPDVRKCMLDAALATLNAHGKENVNSLLPVFEEFLKDAPNDASYDAVRQSVVVLMGSLAKHLDKSDPKVKPIVAKLIAALSTPSQQVQESVASCLPPLVPAVKEDAGGMIQRLMQQLLESDKYAERKGAAYGLAGLVKGLGILSLKQQEMMAALTDAIQDKKNFRRREGALFAFEMLCTMLGKLFEPYVVHVLPHLLLCFGDGNQYVREAADDCAKAVMSNLSAHGVKLVLPSLLAALEEESWRTKAGSVELLGAMAYCAPKQLSSCLPNIVPKLTEVLTDSHVKVQKAGQQALRQIGSVIRNPEILAIAPVLLDALTDPSRKTQKCLQTLLDTKFVHFIDAPSLALIMPIVQRAFQDRSTDTRKMAAQIIGNMYSLTDQKDLAPYLPSVTPGLKASLLDPVPEVRTVSAKALGAMVKGMGESCFEDLLPWLMETLTYEQSSVDRSGAAQGLAEVMAGLGVEKLEKLMPEIVATASKVDIAPHVRDGYIMMFNYLPITFGDKFTPYVGPIIPCILKALADENEFVRDTALRAGQRVISMYAETAIALLLPQLEQGLFDDLWRIRFSSVQLLGDLLFHISGVTGKMTTETASEDDNFGTAQSNKAIITALGVDRRNRVLAGLYMGRSDTQLVVRQASLHVWKIVVSNTPRTLREILPTLFGLLLGFLASTCADKRTIAARTLGDLVRKLGEKILPEIIPILEEGLRSQKSDERQGVCIGLSEIMKSTSRDAVLFFSESLVPTARKALCDPLEEVREAAAKTFEQLHSTIGHQALEDILPFLLKQLDDEEVSEFALDGLKQVMAVKSRVVLPYLVPKLTTPPVNTRVLAFLSSVAGDALTRHLGVILPAVMLALKEKLGTPDEQLEMANCQAVILSVEDDTGHRIIIEDLLEATRSPEVGMRQAAAIILNMYCSRSKADYSSHLRSLVSGLIRLFNDSSPVVLEESWDALNAITKKLDAGNQLALIEELHKEIRFIGNECKGEHVPGFCLPKRGVTSILPVLREGVLTGSPEQKEEAAKGLGLVIRLTSADALRPSVVSITGPLIRILGDRFNWTVKAALLETLSLLLGKVGIALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHVKVDPLFTELLNGIRAVEDPGIRDTMLQALRFVIQGAGSKVDAAIRKNLVSLLLSMLGHDEDNTRISTAGCLGELCAFLTDEELNTVLQQCLLADVSGIDWMVRHGRSLALSVAVNVAPSRLCAGRYSNEVQDMILSNAVADRIPIAMSGIRGMGFLMKYHIETGSGQLPPRLSSLLIKCLQNPCSDIRLVAEKMIWWANKEPRPPLEPQTIKPILKALLDNTKDKNTVVRAYSDQAIVNLLKMRRGEELLQSLSKILDVASLEALNECSRRSLRKLACQADSVEQVDDTILT