E9PVA8 · GCN1_MOUSE
- ProteinStalled ribosome sensor GCN1
- GeneGcn1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids2671 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (By similarity).
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 (By similarity).
In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (By similarity).
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 (PubMed:15937339, PubMed:24333428, PubMed:32324833).
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) (PubMed:24333428, PubMed:32324833).
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 (PubMed:24333428, PubMed:32324833).
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 (By similarity).
In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (By similarity).
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 (PubMed:15937339, PubMed:24333428, PubMed:32324833).
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) (PubMed:24333428, PubMed:32324833).
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 (PubMed:24333428, PubMed:32324833).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | cytosolic ribosome | |
Molecular Function | molecular adaptor activity | |
Molecular Function | protein serine/threonine kinase activator activity | |
Molecular Function | stalled ribosome sensor activity | |
Biological Process | cellular response to amino acid starvation | |
Biological Process | GCN2-mediated signaling | |
Biological Process | protein-RNA covalent cross-linking repair | |
Biological Process | regulation of translation | |
Biological Process | rescue of stalled ribosome |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameStalled ribosome sensor GCN1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionE9PVA8
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Perinatal lethality; mice die at the intermediate stage of embryonic development because of severe growth retardation (PubMed:32324833).
Tamoxifen-inducible deletion in adult mice leads to transient body weight loss associated with decrease of fat and liver glycogen storage (PubMed:35328622).
Tamoxifen-inducible deletion in adult mice leads to transient body weight loss associated with decrease of fat and liver glycogen storage (PubMed:35328622).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 2053-2471 | In Gcn1(DeltaRWDBD) mice; mild growth retardation, leading to death soon after birth, most likely due to respiratory failure. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 151 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000435424 | 2-2671 | Stalled ribosome sensor GCN1 | |||
Sequence: AADTQVSETLKRFAVKVTTASVKERREILSELGRCIAGKDLPEGAVKGLCKLFCLTLHRYRDAASRRALQAAIQQLAEAQPEATAKNLLHSLQSSGVGSKACVPSKSSGSAALLALTWTCLLVRIVFPLKAKRQGDIWNKLVEVQCLLLLEVLGGSHKHAVDGAVKKLTKLWKENPGLVEQYFSAILSLEPSQNYAAMLGLLVQFCTNHKEMDAVSQHKSTLLEFYVKNILMSKAKPPKYLLDNCAPLLRFMSHSEFKDLILPTIQKSLLRSPENVIETISSLLASVTLDLSQYALDIVKGLANQLKSNSPRLMDEAVLALRNLARQCSDSSATEALTKHLFAILGGSEGKLTIIAQKMSVLSGIGSLSHHVVSGPSGQVLNGCVAELFIPFLQQEVHEGTLVHAVSILALWCNRFTTEVPKKLTDWFKKVFSLKTSTSAVRHAYLQCMLASFRGDTLLQALDFLPLLMQTVEKAASQGTQVPTVTEGVAAALLLSKLSVADAQAEAKLSGFWQLVVDEKRQTFTSEKFLLLASEDALCTVLRLTERLFLDHPHRLTNSKVQQYYRVLVAVLLSRTWHVRRQAQQTVRKLLSSLGGVKLANGLLDELKTVLNSHKVLPLEALVTDAGEVTEMGKTYVPPRVLQEALCVISGVPGLKGDIPSTEQLAQEMLIISHHPSLVAVQSGLWPALLTRMKIDPDAFITRHLDQIIPRITTQSPLNQSSMNAMGSLSVLSPDRVLPQLISTITASVQNPALCLVTREEFSIMQTPAGELFDKSIIQSAQQDSIKKANMKRENKAYSFKEQIIEMELKEEIKKKKGIKEEVQLTSKQKEMLQAQMDKEAQIRRRLQELDGELEAALGLLDAIMARNPCGLIQYIPVLVDAFLPLLKSPLAAPRVKGPFLSLAACVMPPRLKTLGTLVSHVTLRLLKPECALDKSWCQEELPVAVRRAVSLLHTHTIPSRVGKGEPDAAPLSAPAFSLVFPMLKMVLTEMPYHSEEEEEQMAQILQILTVHAQLRASPDTPPERVDENGPELLPRVAMLRLLTWVIGTGSPRLQVLASDTLTALCASSSGEDGCAFAEQEEVDVLLAALQSPCASVRETALRGLMELRLVLPSPDTDEKSGLSLLRRLWVIKFDKEDEIRKLAERLWSTMGLDLQSDLCSLLIDDVIYHEAAVRQAGAEALSQAVARYQRQAAEVMGRLMEIYQEKLYRPPPVLDALGRVISESPPDQWEARCGLALALNKLSQYLDSSQVKPLFQFFVPDALNDRNPDVRKCMLDAALATLNAHGKENVNSLLPVFEEFLKDAPNDASYDAVRQSVVVLMGSLAKHLDKSDPKVKPIVAKLIAALSTPSQQVQESVASCLPPLVPAVKEDAGGMIQRLMQQLLESDKYAERKGAAYGLAGLVKGLGILSLKQQEMMAALTDAIQDKKNFRRREGALFAFEMLCTMLGKLFEPYVVHVLPHLLLCFGDGNQYVREAADDCAKAVMSNLSAHGVKLVLPSLLAALEEESWRTKAGSVELLGAMAYCAPKQLSSCLPNIVPKLTEVLTDSHVKVQKAGQQALRQIGSVIRNPEILAIAPVLLDALTDPSRKTQKCLQTLLDTKFVHFIDAPSLALIMPIVQRAFQDRSTDTRKMAAQIIGNMYSLTDQKDLAPYLPSVTPGLKASLLDPVPEVRTVSAKALGAMVKGMGESCFEDLLPWLMETLTYEQSSVDRSGAAQGLAEVMAGLGVEKLEKLMPEIVATASKVDIAPHVRDGYIMMFNYLPITFGDKFTPYVGPIIPCILKALADENEFVRDTALRAGQRVISMYAETAIALLLPQLEQGLFDDLWRIRFSSVQLLGDLLFHISGVTGKMTTETASEDDNFGTAQSNKAIITALGVDRRNRVLAGLYMGRSDTQLVVRQASLHVWKIVVSNTPRTLREILPTLFGLLLGFLASTCADKRTIAARTLGDLVRKLGEKILPEIIPILEEGLRSQKSDERQGVCIGLSEIMKSTSRDAVLFFSESLVPTARKALCDPLEEVREAAAKTFEQLHSTIGHQALEDILPFLLKQLDDEEVSEFALDGLKQVMAVKSRVVLPYLVPKLTTPPVNTRVLAFLSSVAGDALTRHLGVILPAVMLALKEKLGTPDEQLEMANCQAVILSVEDDTGHRIIIEDLLEATRSPEVGMRQAAAIILNMYCSRSKADYSSHLRSLVSGLIRLFNDSSPVVLEESWDALNAITKKLDAGNQLALIEELHKEIRFIGNECKGEHVPGFCLPKRGVTSILPVLREGVLTGSPEQKEEAAKGLGLVIRLTSADALRPSVVSITGPLIRILGDRFNWTVKAALLETLSLLLGKVGIALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHVKVDPLFTELLNGIRAVEDPGIRDTMLQALRFVIQGAGSKVDAAIRKNLVSLLLSMLGHDEDNTRISTAGCLGELCAFLTDEELNTVLQQCLLADVSGIDWMVRHGRSLALSVAVNVAPSRLCAGRYSNEVQDMILSNAVADRIPIAMSGIRGMGFLMKYHIETGSGQLPPRLSSLLIKCLQNPCSDIRLVAEKMIWWANKEPRPPLEPQTIKPILKALLDNTKDKNTVVRAYSDQAIVNLLKMRRGEELLQSLSKILDVASLEALNECSRRSLRKLACQADSVEQVDDTILT | ||||||
Modified residue | 729 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 786 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 2276 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with EIF2AK4/GCN2; this interaction stimulates the EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation (PubMed:24333428).
Interacts with IMPACT; this prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity (PubMed:15937339, PubMed:22404850).
Interacts with RNF14; interaction takes place following ribosome stalling and promotes recruitment of RNF14 (By similarity).
Interacts with IMPACT; this prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity (PubMed:15937339, PubMed:22404850).
Interacts with RNF14; interaction takes place following ribosome stalling and promotes recruitment of RNF14 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, coiled coil, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 140-178 | HEAT 1 | ||||
Sequence: NKLVEVQCLLLLEVLGGSHKHAVDGAVKKLTKLWKENPG | ||||||
Repeat | 257-293 | HEAT 2 | ||||
Sequence: EFKDLILPTIQKSLLRSPENVIETISSLLASVTLDLS | ||||||
Repeat | 294-331 | HEAT 3 | ||||
Sequence: QYALDIVKGLANQLKSNSPRLMDEAVLALRNLARQCSD | ||||||
Repeat | 385-423 | HEAT 4 | ||||
Sequence: CVAELFIPFLQQEVHEGTLVHAVSILALWCNRFTTEVPK | ||||||
Repeat | 425-459 | HEAT 5 | ||||
Sequence: LTDWFKKVFSLKTSTSAVRHAYLQCMLASFRGDTL | ||||||
Repeat | 460-500 | HEAT 6 | ||||
Sequence: LQALDFLPLLMQTVEKAASQGTQVPTVTEGVAAALLLSKLS | ||||||
Repeat | 560-597 | HEAT 7 | ||||
Sequence: SKVQQYYRVLVAVLLSRTWHVRRQAQQTVRKLLSSLGG | ||||||
Repeat | 599-636 | HEAT 8 | ||||
Sequence: KLANGLLDELKTVLNSHKVLPLEALVTDAGEVTEMGKT | ||||||
Repeat | 700-732 | HEAT 9 | ||||
Sequence: AFITRHLDQIIPRITTQSPLNQSSMNAMGSLSV | ||||||
Repeat | 733-772 | HEAT 10 | ||||
Sequence: LSPDRVLPQLISTITASVQNPALCLVTREEFSIMQTPAGE | ||||||
Coiled coil | 804-865 | |||||
Sequence: QIIEMELKEEIKKKKGIKEEVQLTSKQKEMLQAQMDKEAQIRRRLQELDGELEAALGLLDAI | ||||||
Repeat | 879-918 | HEAT 11 | ||||
Sequence: VLVDAFLPLLKSPLAAPRVKGPFLSLAACVMPPRLKTLGT | ||||||
Repeat | 979-1016 | HEAT 12 | ||||
Sequence: SLVFPMLKMVLTEMPYHSEEEEEQMAQILQILTVHAQL | ||||||
Repeat | 1035-1072 | HEAT 13 | ||||
Sequence: LPRVAMLRLLTWVIGTGSPRLQVLASDTLTALCASSSG | ||||||
Repeat | 1078-1115 | HEAT 14 | ||||
Sequence: FAEQEEVDVLLAALQSPCASVRETALRGLMELRLVLPS | ||||||
Repeat | 1155-1192 | HEAT 15 | ||||
Sequence: DLQSDLCSLLIDDVIYHEAAVRQAGAEALSQAVARYQR | ||||||
Repeat | 1210-1250 | HEAT 16 | ||||
Sequence: YRPPPVLDALGRVISESPPDQWEARCGLALALNKLSQYLDS | ||||||
Repeat | 1251-1289 | HEAT 17 | ||||
Sequence: SQVKPLFQFFVPDALNDRNPDVRKCMLDAALATLNAHGK | ||||||
Repeat | 1290-1332 | HEAT 18 | ||||
Sequence: ENVNSLLPVFEEFLKDAPNDASYDAVRQSVVVLMGSLAKHLDK | ||||||
Repeat | 1335-1372 | HEAT 19 | ||||
Sequence: PKVKPIVAKLIAALSTPSQQVQESVASCLPPLVPAVKE | ||||||
Repeat | 1374-1410 | HEAT 20 | ||||
Sequence: AGGMIQRLMQQLLESDKYAERKGAAYGLAGLVKGLGI | ||||||
Repeat | 1413-1451 | HEAT 21 | ||||
Sequence: LKQQEMMAALTDAIQDKKNFRRREGALFAFEMLCTMLGK | ||||||
Repeat | 1455-1492 | HEAT 22 | ||||
Sequence: PYVVHVLPHLLLCFGDGNQYVREAADDCAKAVMSNLSA | ||||||
Repeat | 1493-1530 | HEAT 23 | ||||
Sequence: HGVKLVLPSLLAALEEESWRTKAGSVELLGAMAYCAPK | ||||||
Repeat | 1534-1571 | HEAT 24 | ||||
Sequence: SCLPNIVPKLTEVLTDSHVKVQKAGQQALRQIGSVIRN | ||||||
Repeat | 1573-1609 | HEAT 25 | ||||
Sequence: EILAIAPVLLDALTDPSRKTQKCLQTLLDTKFVHFID | ||||||
Repeat | 1611-1648 | HEAT 26 | ||||
Sequence: PSLALIMPIVQRAFQDRSTDTRKMAAQIIGNMYSLTDQ | ||||||
Repeat | 1653-1690 | HEAT 27 | ||||
Sequence: PYLPSVTPGLKASLLDPVPEVRTVSAKALGAMVKGMGE | ||||||
Repeat | 1692-1729 | HEAT 28 | ||||
Sequence: CFEDLLPWLMETLTYEQSSVDRSGAAQGLAEVMAGLGV | ||||||
Repeat | 1731-1769 | HEAT 29 | ||||
Sequence: KLEKLMPEIVATASKVDIAPHVRDGYIMMFNYLPITFGD | ||||||
Repeat | 1773-1810 | HEAT 30 | ||||
Sequence: PYVGPIIPCILKALADENEFVRDTALRAGQRVISMYAE | ||||||
Repeat | 1812-1848 | HEAT 31 | ||||
Sequence: AIALLLPQLEQGLFDDLWRIRFSSVQLLGDLLFHISG | ||||||
Repeat | 1921-1958 | HEAT 32 | ||||
Sequence: EILPTLFGLLLGFLASTCADKRTIAARTLGDLVRKLGE | ||||||
Repeat | 1959-1996 | HEAT 33 | ||||
Sequence: KILPEIIPILEEGLRSQKSDERQGVCIGLSEIMKSTSR | ||||||
Repeat | 2001-2038 | HEAT 34 | ||||
Sequence: FFSESLVPTARKALCDPLEEVREAAAKTFEQLHSTIGH | ||||||
Repeat | 2039-2074 | HEAT 35 | ||||
Sequence: QALEDILPFLLKQLDDEEVSEFALDGLKQVMAVKSR | ||||||
Repeat | 2076-2108 | HEAT 36 | ||||
Sequence: VLPYLVPKLTTPPVNTRVLAFLSSVAGDALTRH | ||||||
Repeat | 2111-2146 | HEAT 37 | ||||
Sequence: VILPAVMLALKEKLGTPDEQLEMANCQAVILSVEDD | ||||||
Repeat | 2147-2184 | HEAT 38 | ||||
Sequence: TGHRIIIEDLLEATRSPEVGMRQAAAIILNMYCSRSKA | ||||||
Repeat | 2188-2225 | HEAT 39 | ||||
Sequence: SHLRSLVSGLIRLFNDSSPVVLEESWDALNAITKKLDA | ||||||
Repeat | 2259-2296 | HEAT 40 | ||||
Sequence: RGVTSILPVLREGVLTGSPEQKEEAAKGLGLVIRLTSA | ||||||
Region | 2260-2408 | RWDBD region | ||||
Sequence: GVTSILPVLREGVLTGSPEQKEEAAKGLGLVIRLTSADALRPSVVSITGPLIRILGDRFNWTVKAALLETLSLLLGKVGIALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHVKVDPLFTELLNGIRAVEDPGIRDTMLQAL | ||||||
Repeat | 2301-2338 | HEAT 41 | ||||
Sequence: PSVVSITGPLIRILGDRFNWTVKAALLETLSLLLGKVG | ||||||
Repeat | 2339-2380 | HEAT 42 | ||||
Sequence: IALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHVK | ||||||
Repeat | 2382-2417 | HEAT 43 | ||||
Sequence: DPLFTELLNGIRAVEDPGIRDTMLQALRFVIQGAGS | ||||||
Repeat | 2422-2459 | HEAT 44 | ||||
Sequence: AIRKNLVSLLLSMLGHDEDNTRISTAGCLGELCAFLTD | ||||||
Repeat | 2546-2583 | HEAT 45 | ||||
Sequence: QLPPRLSSLLIKCLQNPCSDIRLVAEKMIWWANKEPRP | ||||||
Repeat | 2588-2625 | HEAT 46 | ||||
Sequence: QTIKPILKALLDNTKDKNTVVRAYSDQAIVNLLKMRRG | ||||||
Repeat | 2627-2661 | HEAT 47 | ||||
Sequence: ELLQSLSKILDVASLEALNECSRRSLRKLACQADS |
Domain
The RWDBD (RWD-binding domain) region mediates binding to RWD domain-containing proteins, such as EIF2AK4/GCN2, IMPACT and RNF14.
Sequence similarities
Belongs to the GCN1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,671
- Mass (Da)293,021
- Last updated2011-04-05 v1
- Checksum77B317C0797DC5A7
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 466 | in Ref. 2; AAI50736 | ||||
Sequence: L → V | ||||||
Sequence conflict | 537 | in Ref. 2; AAI50736 | ||||
Sequence: D → E | ||||||
Sequence conflict | 1477 | in Ref. 2; AAI50736 | ||||
Sequence: E → K | ||||||
Sequence conflict | 2544 | in Ref. 2; AAI50736 | ||||
Sequence: S → G | ||||||
Sequence conflict | 2583 | in Ref. 2; AAI50736 | ||||
Sequence: P → H |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC159539 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC150735 EMBL· GenBank· DDBJ | AAI50736.1 EMBL· GenBank· DDBJ | mRNA |