E9PVA8 · GCN1_MOUSE

  • Protein
    Stalled ribosome sensor GCN1
  • Gene
    Gcn1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentcytosolic ribosome
Molecular Functionmolecular adaptor activity
Molecular Functionprotein serine/threonine kinase activator activity
Molecular Functionstalled ribosome sensor activity
Biological Processcellular response to amino acid starvation
Biological ProcessGCN2-mediated signaling
Biological Processprotein-RNA covalent cross-linking repair
Biological Processregulation of translation
Biological Processrescue of stalled ribosome

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Stalled ribosome sensor GCN1
  • Alternative names
    • GCN1 eIF-2-alpha kinase activator homolog
    • GCN1-like protein 1
    • General control of amino-acid synthesis 1-like protein 1
    • Translational activator GCN1

Gene names

    • Name
      Gcn1
    • Synonyms
      Gcn1l1

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    E9PVA8
  • Secondary accessions
    • B2RWW6

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Note: Associates with ribosomes in undifferentiated neuroblastoma cells and increases after neuronal differentiation (PubMed:23447528).

Keywords

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis2053-2471In Gcn1(DeltaRWDBD) mice; mild growth retardation, leading to death soon after birth, most likely due to respiratory failure.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00004354242-2671Stalled ribosome sensor GCN1
Modified residue729Phosphoserine
Modified residue786Phosphoserine
Modified residue2276Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in the hypothalamus, cortex and hippocampus (PubMed:15937339).

Gene expression 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).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for repeat, coiled coil, region.

TypeIDPosition(s)Description
Repeat140-178HEAT 1
Repeat257-293HEAT 2
Repeat294-331HEAT 3
Repeat385-423HEAT 4
Repeat425-459HEAT 5
Repeat460-500HEAT 6
Repeat560-597HEAT 7
Repeat599-636HEAT 8
Repeat700-732HEAT 9
Repeat733-772HEAT 10
Coiled coil804-865
Repeat879-918HEAT 11
Repeat979-1016HEAT 12
Repeat1035-1072HEAT 13
Repeat1078-1115HEAT 14
Repeat1155-1192HEAT 15
Repeat1210-1250HEAT 16
Repeat1251-1289HEAT 17
Repeat1290-1332HEAT 18
Repeat1335-1372HEAT 19
Repeat1374-1410HEAT 20
Repeat1413-1451HEAT 21
Repeat1455-1492HEAT 22
Repeat1493-1530HEAT 23
Repeat1534-1571HEAT 24
Repeat1573-1609HEAT 25
Repeat1611-1648HEAT 26
Repeat1653-1690HEAT 27
Repeat1692-1729HEAT 28
Repeat1731-1769HEAT 29
Repeat1773-1810HEAT 30
Repeat1812-1848HEAT 31
Repeat1921-1958HEAT 32
Repeat1959-1996HEAT 33
Repeat2001-2038HEAT 34
Repeat2039-2074HEAT 35
Repeat2076-2108HEAT 36
Repeat2111-2146HEAT 37
Repeat2147-2184HEAT 38
Repeat2188-2225HEAT 39
Repeat2259-2296HEAT 40
Region2260-2408RWDBD region
Repeat2301-2338HEAT 41
Repeat2339-2380HEAT 42
Repeat2382-2417HEAT 43
Repeat2422-2459HEAT 44
Repeat2546-2583HEAT 45
Repeat2588-2625HEAT 46
Repeat2627-2661HEAT 47

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,671
  • Mass (Da)
    293,021
  • Last updated
    2011-04-05 v1
  • Checksum
    77B317C0797DC5A7
MAADTQVSETLKRFAVKVTTASVKERREILSELGRCIAGKDLPEGAVKGLCKLFCLTLHRYRDAASRRALQAAIQQLAEAQPEATAKNLLHSLQSSGVGSKACVPSKSSGSAALLALTWTCLLVRIVFPLKAKRQGDIWNKLVEVQCLLLLEVLGGSHKHAVDGAVKKLTKLWKENPGLVEQYFSAILSLEPSQNYAAMLGLLVQFCTNHKEMDAVSQHKSTLLEFYVKNILMSKAKPPKYLLDNCAPLLRFMSHSEFKDLILPTIQKSLLRSPENVIETISSLLASVTLDLSQYALDIVKGLANQLKSNSPRLMDEAVLALRNLARQCSDSSATEALTKHLFAILGGSEGKLTIIAQKMSVLSGIGSLSHHVVSGPSGQVLNGCVAELFIPFLQQEVHEGTLVHAVSILALWCNRFTTEVPKKLTDWFKKVFSLKTSTSAVRHAYLQCMLASFRGDTLLQALDFLPLLMQTVEKAASQGTQVPTVTEGVAAALLLSKLSVADAQAEAKLSGFWQLVVDEKRQTFTSEKFLLLASEDALCTVLRLTERLFLDHPHRLTNSKVQQYYRVLVAVLLSRTWHVRRQAQQTVRKLLSSLGGVKLANGLLDELKTVLNSHKVLPLEALVTDAGEVTEMGKTYVPPRVLQEALCVISGVPGLKGDIPSTEQLAQEMLIISHHPSLVAVQSGLWPALLTRMKIDPDAFITRHLDQIIPRITTQSPLNQSSMNAMGSLSVLSPDRVLPQLISTITASVQNPALCLVTREEFSIMQTPAGELFDKSIIQSAQQDSIKKANMKRENKAYSFKEQIIEMELKEEIKKKKGIKEEVQLTSKQKEMLQAQMDKEAQIRRRLQELDGELEAALGLLDAIMARNPCGLIQYIPVLVDAFLPLLKSPLAAPRVKGPFLSLAACVMPPRLKTLGTLVSHVTLRLLKPECALDKSWCQEELPVAVRRAVSLLHTHTIPSRVGKGEPDAAPLSAPAFSLVFPMLKMVLTEMPYHSEEEEEQMAQILQILTVHAQLRASPDTPPERVDENGPELLPRVAMLRLLTWVIGTGSPRLQVLASDTLTALCASSSGEDGCAFAEQEEVDVLLAALQSPCASVRETALRGLMELRLVLPSPDTDEKSGLSLLRRLWVIKFDKEDEIRKLAERLWSTMGLDLQSDLCSLLIDDVIYHEAAVRQAGAEALSQAVARYQRQAAEVMGRLMEIYQEKLYRPPPVLDALGRVISESPPDQWEARCGLALALNKLSQYLDSSQVKPLFQFFVPDALNDRNPDVRKCMLDAALATLNAHGKENVNSLLPVFEEFLKDAPNDASYDAVRQSVVVLMGSLAKHLDKSDPKVKPIVAKLIAALSTPSQQVQESVASCLPPLVPAVKEDAGGMIQRLMQQLLESDKYAERKGAAYGLAGLVKGLGILSLKQQEMMAALTDAIQDKKNFRRREGALFAFEMLCTMLGKLFEPYVVHVLPHLLLCFGDGNQYVREAADDCAKAVMSNLSAHGVKLVLPSLLAALEEESWRTKAGSVELLGAMAYCAPKQLSSCLPNIVPKLTEVLTDSHVKVQKAGQQALRQIGSVIRNPEILAIAPVLLDALTDPSRKTQKCLQTLLDTKFVHFIDAPSLALIMPIVQRAFQDRSTDTRKMAAQIIGNMYSLTDQKDLAPYLPSVTPGLKASLLDPVPEVRTVSAKALGAMVKGMGESCFEDLLPWLMETLTYEQSSVDRSGAAQGLAEVMAGLGVEKLEKLMPEIVATASKVDIAPHVRDGYIMMFNYLPITFGDKFTPYVGPIIPCILKALADENEFVRDTALRAGQRVISMYAETAIALLLPQLEQGLFDDLWRIRFSSVQLLGDLLFHISGVTGKMTTETASEDDNFGTAQSNKAIITALGVDRRNRVLAGLYMGRSDTQLVVRQASLHVWKIVVSNTPRTLREILPTLFGLLLGFLASTCADKRTIAARTLGDLVRKLGEKILPEIIPILEEGLRSQKSDERQGVCIGLSEIMKSTSRDAVLFFSESLVPTARKALCDPLEEVREAAAKTFEQLHSTIGHQALEDILPFLLKQLDDEEVSEFALDGLKQVMAVKSRVVLPYLVPKLTTPPVNTRVLAFLSSVAGDALTRHLGVILPAVMLALKEKLGTPDEQLEMANCQAVILSVEDDTGHRIIIEDLLEATRSPEVGMRQAAAIILNMYCSRSKADYSSHLRSLVSGLIRLFNDSSPVVLEESWDALNAITKKLDAGNQLALIEELHKEIRFIGNECKGEHVPGFCLPKRGVTSILPVLREGVLTGSPEQKEEAAKGLGLVIRLTSADALRPSVVSITGPLIRILGDRFNWTVKAALLETLSLLLGKVGIALKPFLPQLQTTFTKALQDSNRGVRLKAADALGKLISIHVKVDPLFTELLNGIRAVEDPGIRDTMLQALRFVIQGAGSKVDAAIRKNLVSLLLSMLGHDEDNTRISTAGCLGELCAFLTDEELNTVLQQCLLADVSGIDWMVRHGRSLALSVAVNVAPSRLCAGRYSNEVQDMILSNAVADRIPIAMSGIRGMGFLMKYHIETGSGQLPPRLSSLLIKCLQNPCSDIRLVAEKMIWWANKEPRPPLEPQTIKPILKALLDNTKDKNTVVRAYSDQAIVNLLKMRRGEELLQSLSKILDVASLEALNECSRRSLRKLACQADSVEQVDDTILT

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict466in Ref. 2; AAI50736
Sequence conflict537in Ref. 2; AAI50736
Sequence conflict1477in Ref. 2; AAI50736
Sequence conflict2544in Ref. 2; AAI50736
Sequence conflict2583in Ref. 2; AAI50736

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AC159539
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC150735
EMBL· GenBank· DDBJ
AAI50736.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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