Protein: Stalled ribosome sensor GCN1 (Q92616)
Organism: Homo sapiens (Human)
Function: Ribosome collision sensor that plays a key role in the RNF14- RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes. Directly binds to the ribosome and acts as a sentinel for colliding ribosomes: activated following ribosome stalling and promotes recruitment of RNF14, which directly ubiquitinates EEF1A1/eEF1A, leading to its degradation. In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein. GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (By similarity). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) (By similarity). EIF2S1/eIF-2-alpha phosphorylation 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)
Subcellular location: Cytoplasm. Note=Associates with ribosomes in undifferentiated neuroblastoma cells and increases after neuronal differentiation
Sequence: MAADTQVSETLKRFAGKVTTASVKERREILSELGKCVAGKDLPEGAVKGLCKLFCLTLHRYRDAASRRALQAAIQQLAEAQPEATAKNLLHSLQSSGIGSKAGVPSKSSGSAALLALTWTCLLVRIVFPSRAKRQGDIWNKLVEVQCLLLLEVLGGSHKHAVDGAVKKLTKLWKENPGLVEQYLSAILSLEPNQNYAGMLGLLVQFCTSHKEMDVVSQHKSALLDFYMKNILMSKVKPPKYLLDSCAPLLRYLSHSEFKDLILPTIQKSLLRSPENVIETISSLLASVTLDLSQYAMDIVKGLAGHLKSNSPRLMDEAVLALRNLARQCSDSSAMESLTKHLFAILGGSEGKLTVVAQKMSVLSGIGSVSHHVVSGPSSQVLNGIVAELFIPFLQQEVHEGTLVHAVSVLALWCNRFTMEVPKKLTEWFKKAFSLKTSTSAVRHAYLQCMLASYRGDTLLQALDLLPLLIQTVEKAASQSTQVPTITEGVAAALLLLKLSVADSQAEAKLSSFWQLIVDEKKQVFTSEKFLVMASEDALCTVLHLTERLFLDHPHRLTGNKVQQYHRALVAVLLSRTWHVRRQAQQTVRKLLSSLGGFKLAHGLLEELKTVLSSHKVLPLEALVTDAGEVTEAGKAYVPPRVLQEALCVISGVPGLKGDVTDTEQLAQEMLIISHHPSLVAVQSGLWPALLARMKIDPEAFITRHLDQIIPRMTTQSPLNQSSMNAMGSLSVLSPDRVLPQLISTITASVQNPALRLVTREEFAIMQTPAGELYDKSIIQSAQQDSIKKANMKRENKAYSFKEQIIELELKEEIKKKKGIKEEVQLTSKQKEMLQAQLDREAQVRRRLQELDGELEAALGLLDIILAKNPSGLTQYIPVLVDSFLPLLKSPLAAPRIKNPFLSLAACVMPSRLKALGTLVSHVTLRLLKPECVLDKSWCQEELSVAVKRAVMLLHTHTITSRVGKGEPGAAPLSAPAFSLVFPFLKMVLTEMPHHSEEEEEWMAQILQILTVQAQLRASPNTPPGRVDENGPELLPRVAMLRLLTWVIGTGSPRLQVLASDTLTTLCASSSGDDGCAFAEQEEVDVLLCALQSPCASVRETVLRGLMELHMVLPAPDTDEKNGLNLLRRLWVVKFDKEEEIRKLAERLWSMMGLDLQPDLCSLLIDDVIYHEAAVRQAGAEALSQAVARYQRQAAEVMGRLMEIYQEKLYRPPPVLDALGRVISESPPDQWEARCGLALALNKLSQYLDSSQVKPLFQFFVPDALNDRHPDVRKCMLDAALATLNTHGKENVNSLLPVFEEFLKNAPNDASYDAVRQSVVVLMGSLAKHLDKSDPKVKPIVAKLIAALSTPSQQVQESVASCLPPLVPAIKEDAGGMIQRLMQQLLESDKYAERKGAAYGLAGLVKGLGILSLKQQEMMAALTDAIQDKKNFRRREGALFAFEMLCTMLGKLFEPYVVHVLPHLLLCFGDGNQYVREAADDCAKAVMSNLSAHGVKLVLPSLLAALEEESWRTKAGSVELLGAMAYCAPKQLSSCLPNIVPKLTEVLTDSHVKVQKAGQQALRQIGSVIRNPEILAIAPVLLDALTDPSRKTQKCLQTLLDTKFVHFIDAPSLALIMPIVQRAFQDRSTDTRKMAAQIIGNMYSLTDQKDLAPYLPSVTPGLKASLLDPVPEVRTVSAKALGAMVKGMGESCFEDLLPWLMETLTYEQSSVDRSGAAQGLAEVMAGLGVEKLEKLMPEIVATASKVDIAPHVRDGYIMMFNYLPITFGDKFTPYVGPIIPCILKALADENEFVRDTALRAGQRVISMYAETAIALLLPQLEQGLFDDLWRIRFSSVQLLGDLLFHISGVTGKMTTETASEDDNFGTAQSNKAIITALGVERRNRVLAGLYMGRSDTQLVVRQASLHVWKIVVSNTPRTLREILPTLFGLLLGFLASTCADKRTIAARTLGDLVRKLGEKILPEIIPILEEGLRSQKSDERQGVCIGLSEIMKSTSRDAVLYFSESLVPTARKALCDPLEEVREAAAKTFEQLHSTIGHQALEDILPFLLKQLDDEEVSEFALDGLKQVMAIKSRVVLPYLVPKLTTPPVNTRVLAFLSSVAGDALTRHLGVILPAVMLALKEKLGTPDEQLEMANCQAVILSVEDDTGHRIIIEDLLEATRSPEVGMRQAAAIILNIYCSRSKADYTSHLRSLVSGLIRLFNDSSPVVLEESWDALNAITKKLDAGNQLALIEELHKEIRLIGNESKGEHVPGFCLPKKGVTSILPVLREGVLTGSPEQKEEAAKALGLVIRLTSADALRPSVVSITGPLIRILGDRFSWNVKAALLETLSLLLAKVGIALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHIKVDPLFTELLNGIRAMEDPGVRDTMLQALRFVIQGAGAKVDAVIRKNIVSLLLSMLGHDEDNTRISSAGCLGELCAFLTEEELSAVLQQCLLADVSGIDWMVRHGRSLALSVAVNVAPGRLCAGRYSSDVQEMILSSATADRIPIAVSGVRGMGFLMRHHIETGGGQLPAKLSSLFVKCLQNPSSDIRLVAEKMIWWANKDPLPPLDPQAIKPILKALLDNTKDKNTVVRAYSDQAIVNLLKMRQGEEVFQSLSKILDVASLEVLNEVNRRSLKKLASQADSTEQVDDTILT
InterPro domains: - IPR057546: Stalled ribosome sensor GCN1-like, HEAT repeats region (domain) [2076-2258]
- IPR016024: Armadillo-type fold (homologous_superfamily) [148-2637]
- IPR011989: Armadillo-like helical (homologous_superfamily) [133-2664]
- IPR034085: TOG domain (domain) [1365-1598]
- IPR021133: HEAT, type 2 (repeat) [1616-2043]
- IPR056810: Stalled ribosome sensor GCN1-like, N-terminal (domain) [220-353]
Interaction partners: - eIF-2-alpha kinase GCN2
- ATP-binding cassette sub-family F member 3
- Developmentally-regulated GTP-binding protein 2
- Small ribosomal subunit protein uS3
- Small ribosomal subunit protein uS15
- Small ribosomal subunit protein uS19
- Small ribosomal subunit protein uS5
- Small ribosomal subunit protein uS10
- Large ribosomal subunit protein eL19
- Small ribosomal subunit protein eS12
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0045182 (translation regulator activity), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0090079 (translation regulator activity, nucleic acid binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0050896 (response to stimulus), GO:0009605 (response to external stimulus), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0007154 (cell communication), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0009991 (response to extracellular stimulus), GO:0031668 (cellular response to extracellular stimulus), GO:0042127 (regulation of cell population proliferation), GO:0042594 (response to starvation), GO:0071496 (cellular response to external stimulus), GO:0033554 (cellular response to stress), GO:0008284 (positive regulation of cell population proliferation), GO:1990928 (response to amino acid starvation), GO:0031669 (cellular response to nutrient levels), GO:0009267 (cellular response to starvation), GO:0031667 (response to nutrient levels), GO:0034198 (cellular response to amino acid starvation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:1990904 (ribonucleoprotein complex), GO:0005737 (cytoplasm), GO:0005844 (polysome)