eIF-2-alpha kinase GCN2

Details

Name
eIF-2-alpha kinase GCN2
Synonyms
  • 2.7.11.1
  • Eukaryotic translation initiation factor 2-alpha kinase 4
  • GCN2
  • GCN2-like protein
  • KIAA1338
Gene Name
EIF2AK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051748|eIF-2-alpha kinase GCN2
MAGGRGAPGRGRDEPPESYPQRQDHELQALEAIYGADFQDLRPDACGPVKEPPEINLVLY
PQGLTGEEVYVKVDLRVKCPPTYPDVVPEIELKNAKGLSNESVNLLKSRLEELAKKHCGE
VMIFELAYHVQSFLSEHNKPPPKSFHEEMLERRAQEEQQRLLEAKRKEEQEQREILHEIQ
RRKEEIKEEKKRKEMAKQERLEIASLSNQDHTSKKDPGGHRTAAILHGGSPDFVGNGKHR
ANSSGRSRRERQYSVCNSEDSPGSCEILYFNMGSPDQLMVHKGKCIGSDEQLGKLVYNAL
ETATGGFVLLYEWVLQWQKKMGPFLTSQEKEKIDKCKKQIQGTETEFNSLVKLSHPNVVR
YLAMNLKEQDDSIVVDILVEHISGVSLAAHLSHSGPIPVHQLRRYTAQLLSGLDYLHSNS
VVHKVLSASNVLVDAEGTVKITDYSISKRLADICKEDVFEQTRVRFSDNALPYKTGKKGD
VWRLGLLLLSLSQGQECGEYPVTIPSDLPADFQDFLKKCVCLDDKERWSPQQLLKHSFIN
PQPKMPLVEQSPEDSEGQDYVETVIPSNRLPSAAFFSETQRQFSRYFIEFEELQLLGKGA
FGAVIKVQNKLDGCCYAVKRIPINPASRQFRRIKGEVTLLSRLHHENIVRYYNAWIERHE
RPAGPGTPPPDSGPLAKDDRAARGQPASDTDGLDSVEAAAPPPILSSSVEWSTSGERSAS
ARFPATGPGSSDDEDDDEDEHGGVFSQSFLPASDSESDIIFDNEDENSKSQNQDEDCNEK
NGCHESEPSVTTEAVHYLYIQMEYCEKSTLRDTIDQGLYRDTVRLWRLFREILDGLAYIH
EKGMIHRDLKPVNIFLDSDDHVKIGDFGLATDHLAFSADSKQDDQTGDLIKSDPSGHLTG
MVGTALYVSPEVQGSTKSAYNQKVDLFSLGIIFFEMSYHPMVTASERIFVLNQLRDPTSP
KFPEDFDDGEHAKQKSVISWLLNHDPAKRPTATELLKSELLPPPQMEESELHEVLHHTLT
NVDGKAYRTMMAQIFSQRISPAIDYTYDSDILKGNFSIRTAKMQQHVCETIIRIFKRHGA
VQLCTPLLLPRNRQIYEHNEAALFMDHSGMLVMLPFDLRIPFARYVARNNILNLKRYCIE
RVFRPRKLDRFHPKELLECAFDIVTSTTNSFLPTAEIIYTIYEIIQEFPALQERNYSIYL
NHTMLLKAILLHCGIPEDKLSQVYIILYDAVTEKLTRREVEAKFCNLSLSSNSLCRLYKF
IEQKGDLQDLMPTINSLIKQKTGIAQLVKYGLKDLEEVVGLLKKLGIKLQVLINLGLVYK
VQQHNGIIFQFVAFIKRRQRAVPEILAAGGRYDLLIPQFRGPQALGPVPTAIGVSIAIDK
ISAAVLNMEESVTISSCDLLVVSVGQMSMSRAINLTQKLWTAGITAEIMYDWSQSQEELQ
EYCRHHEITYVALVSDKEGSHVKVKSFEKERQTEKRVLETELVDHVLQKLRTKVTDERNG
REASDNLAVQNLKGSFSNASGLFEIHGATVVPIVSVLAPEKLSASTRRRYETQVQTRLQT
SLANLHQKSSEIEILAVDLPKETILQFLSLEWDADEQAFNTTVKQLLSRLPKQRYLKLVC
DEIYNIKVEKKVSVLFLYSYRDDYYRILF
Number of residues
1649
Molecular Weight
186908.89
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / eukaryotic translation initiation factor 2alpha kinase activity / protein serine/threonine kinase activity / tRNA binding
Processes
adaptive immune response / cell cycle arrest / cellular response to amino acid starvation / cellular response to cold / cellular response to leucine starvation / cellular response to UV / defense response to virus / DNA damage checkpoint / eiF2alpha phosphorylation in response to endoplasmic reticulum stress / induction by virus of host autophagy / learning / long-term memory / negative regulation by host of viral genome replication / negative regulation of CREB transcription factor activity / negative regulation of neuron differentiation / negative regulation of translational initiation / negative regulation of translational initiation in response to stress / neuron projection extension / positive regulation of adaptive immune response / positive regulation of defense response to virus by host / positive regulation of long-term synaptic potentiation / positive regulation of translational initiation in response to starvation / protein autophosphorylation / protein phosphorylation / regulation of eIF2 alpha phosphorylation by amino acid starvation / regulation of feeding behavior / regulation of translational initiation / regulation of translational initiation by eIF2 alpha phosphorylation / T cell activation involved in immune response / viral translation
Components
cytosolic ribosome / polysome
General Function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. 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 (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory. Plays a role in neurite outgrowth inhibition. Plays a proapoptotic role in response to glucose deprivation. 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).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051749|eIF-2-alpha kinase GCN2 (EIF2AK4)
ATGGCTGGGGGCCGTGGGGCCCCCGGGCGCGGCCGGGACGAGCCTCCGGAGAGCTACCCG
CAACGACAGGACCACGAGCTACAGGCCCTGGAGGCCATTTACGGCGCGGACTTCCAAGAC
CTGCGGCCGGACGCTTGCGGACCGGTCAAAGAGCCCCCTGAAATCAATTTAGTTTTGTAC
CCTCAAGGCCTAACTGGTGAAGAAGTATATGTAAAAGTGGATTTGAGGGTTAAATGCCCA
CCTACCTATCCAGATGTAGTTCCTGAAATAGAGTTAAAAAATGCCAAAGGTCTATCAAAT
GAAAGTGTCAATTTGTTAAAATCTCGCCTAGAAGAACTGGCCAAGAAACACTGTGGGGAG
GTGATGATCTTTGAACTGGCTTACCACGTGCAGTCATTTCTCAGCGAGCATAACAAGCCC
CCTCCCAAGTCTTTTCATGAAGAAATGCTGGAAAGGCGGGCTCAGGAGGAGCAGCAGAGG
CTGTTGGAGGCCAAGCGGAAAGAAGAGCAGGAGCAACGTGAAATCCTGCATGAGATTCAG
AGAAGGAAAGAAGAGATAAAAGAAGAGAAAAAAAGGAAAGAAATGGCTAAGCAGGAACGT
TTGGAAATTGCTAGTTTGTCAAACCAAGATCATACCTCTAAGAAGGACCCAGGAGGACAC
AGAACGGCTGCCATTCTACATGGAGGCTCTCCTGACTTTGTAGGAAATGGTAAACATCGG
GCAAACTCCTCAGGAAGGTCTAGGCGAGAACGTCAGTATTCTGTATGTAATAGTGAAGAT
TCTCCTGGCTCTTGTGAAATTCTGTATTTCAATATGGGGAGTCCTGATCAGCTCATGGTG
CACAAAGGGAAATGTATTGGCAGTGATGAACAACTTGGAAAATTAGTCTACAATGCTTTG
GAAACAGCCACTGGTGGCTTTGTCTTGTTGTATGAGTGGGTCCTTCAGTGGCAGAAAAAA
ATGGGTCCATTCCTTACCAGTCAAGAAAAAGAGAAGATTGATAAGTGCAAAAAGCAGATT
CAAGGAACAGAAACAGAATTCAACTCACTGGTAAAATTGAGCCATCCAAATGTAGTACGC
TACCTTGCAATGAATCTCAAAGAGCAAGACGACTCCATCGTGGTGGACATTTTAGTGGAG
CACATTAGTGGGGTCTCTCTTGCTGCACACCTGAGCCACTCAGGCCCCATCCCTGTGCAT
CAGCTTCGCAGGTACACAGCTCAGCTCCTGTCAGGCCTTGATTATCTGCACAGCAATTCT
GTGGTGCATAAGGTCCTGAGTGCATCTAATGTCTTGGTGGATGCAGAAGGCACCGTCAAG
ATTACGGACTATAGCATTTCTAAGCGCCTCGCAGACATTTGCAAGGAGGATGTGTTTGAG
CAAACCCGAGTTCGTTTTAGTGACAATGCTCTGCCTTATAAAACGGGGAAGAAAGGAGAT
GTTTGGCGTCTTGGCCTTCTGCTGCTGTCCCTCAGCCAAGGACAGGAATGTGGAGAGTAC
CCTGTGACCATCCCTAGTGACTTACCAGCTGACTTTCAAGATTTTCTAAAGAAATGTGTG
TGCTTGGATGACAAGGAAAGATGGAGTCCCCAGCAGTTGTTGAAACACAGCTTTATAAAT
CCCCAGCCAAAAATGCCTCTAGTGGAACAAAGTCCTGAAGATTCTGAAGGACAAGATTAT
GTTGAGACTGTTATTCCTAGCAACCGGCTACCCAGTGCTGCCTTCTTTAGTGAGACACAG
AGACAGTTTTCCCGATACTTCATTGAGTTTGAAGAATTACAACTTCTTGGTAAAGGAGCT
TTTGGAGCTGTCATCAAGGTGCAGAACAAGTTGGACGGCTGCTGCTACGCAGTGAAGCGC
ATCCCCATCAACCCGGCCAGCCGGCAGTTCCGCAGGATCAAGGGCGAAGTGACACTGCTG
TCACGGCTGCACCATGAGAACATTGTGCGCTACTACAACGCCTGGATCGAGCGGCACGAG
CGGCCGGCGGGACCGGGGACGCCGCCCCCGGACTCCGGGCCCCTGGCCAAGGATGACCGA
GCTGCACGCGGGCAGCCGGCGAGCGACACAGACGGCCTGGACAGCGTAGAGGCCGCCGCG
CCGCCACCCATCCTCAGCAGCTCGGTGGAGTGGAGCACTTCGGGCGAGCGCTCGGCCAGT
GCCCGTTTCCCCGCCACCGGCCCGGGCTCCAGCGATGACGAGGACGACGACGAGGACGAG
CACGGTGGCGTCTTCTCCCAGTCCTTCCTGCCTGCTTCAGATTCTGAAAGTGATATTATC
TTTGACAATGAAGATGAGAACAGTAAAAGTCAGAATCAGGATGAAGATTGCAATGAAAAG
AATGGCTGCCATGAAAGTGAGCCATCAGTGACGACTGAGGCTGTGCACTACCTATACATC
CAGATGGAGTACTGTGAGAAGAGCACTTTACGAGACACCATTGACCAGGGACTGTATCGA
GACACCGTCAGACTCTGGAGGCTTTTTCGAGAGATTCTGGATGGATTAGCTTATATCCAT
GAGAAAGGAATGATTCACCGGGATTTGAAGCCTGTCAACATTTTTTTGGATTCTGATGAC
CATGTGAAAATAGGTGATTTTGGTTTGGCGACAGACCATCTAGCCTTTTCTGCTGACAGC
AAACAAGACGATCAGACAGGAGACTTGATTAAGTCAGACCCTTCAGGTCACTTAACTGGG
ATGGTTGGCACTGCTCTCTATGTAAGCCCAGAGGTCCAAGGAAGCACCAAATCTGCATAC
AACCAGAAAGTGGATCTCTTCAGCCTGGGAATTATCTTCTTTGAGATGTCCTATCACCCC
ATGGTCACGGCTTCAGAAAGGATCTTTGTTCTCAACCAACTCAGAGATCCCACTTCGCCT
AAGTTTCCAGAAGACTTTGACGATGGAGAGCATGCAAAGCAGAAATCAGTCATCTCCTGG
CTGTTGAACCACGATCCAGCAAAACGGCCCACAGCCACAGAACTGCTCAAGAGTGAGCTG
CTGCCCCCACCCCAGATGGAGGAGTCAGAGCTGCATGAAGTGCTGCACCACACGCTGACC
AACGTGGATGGGAAGGCCTACCGCACCATGATGGCCCAGATCTTCTCGCAGCGCATCTCC
CCTGCCATCGATTACACCTATGACAGCGACATACTGAAGGGCAACTTCTCAATCCGTACA
GCCAAGATGCAGCAGCATGTGTGTGAAACCATCATCCGCATCTTTAAAAGACATGGAGCT
GTTCAGTTGTGTACTCCACTACTGCTTCCCCGAAACAGACAAATATATGAGCACAACGAA
GCTGCCCTATTCATGGACCACAGCGGGATGCTGGTGATGCTTCCTTTTGACCTGCGGATC
CCTTTTGCAAGATATGTGGCAAGAAATAATATATTGAATTTAAAACGATACTGCATAGAA
CGTGTGTTCAGGCCGCGCAAGTTAGATCGATTTCATCCCAAAGAACTTCTGGAGTGTGCA
TTTGATATTGTCACTTCTACCACCAACAGCTTTCTGCCCACTGCTGAAATTATCTACACT
ATCTATGAAATCATCCAAGAGTTTCCAGCACTTCAGGAAAGAAATTACAGTATTTATTTG
AACCATACCATGTTATTGAAAGCAATACTCTTACACTGTGGGATCCCAGAAGATAAACTC
AGTCAAGTCTACATTATTCTGTATGATGCTGTGACAGAGAAGCTGACGAGGAGAGAAGTG
GAAGCTAAATTTTGTAATCTGTCTTTGTCTTCTAATAGTCTGTGTCGACTCTACAAGTTT
ATTGAACAGAAGGGAGATTTGCAAGATCTTATGCCAACAATAAATTCATTAATAAAACAG
AAAACAGGTATTGCACAGTTGGTGAAGTATGGCTTAAAAGACCTAGAGGAGGTTGTTGGA
CTGTTGAAGAAACTCGGCATCAAGTTACAGGTCTTGATCAATTTGGGCTTGGTTTACAAG
GTGCAGCAGCACAATGGAATCATCTTCCAGTTTGTGGCTTTCATCAAACGAAGGCAAAGG
GCTGTACCTGAAATCCTCGCAGCTGGAGGCAGATATGACCTGCTGATTCCCCAGTTTAGA
GGGCCACAAGCTCTGGGGCCAGTTCCCACTGCCATTGGGGTCAGCATAGCTATAGACAAG
ATATCTGCTGCTGTCCTCAACATGGAGGAATCTGTTACAATAAGCTCTTGTGACCTCCTG
GTTGTAAGTGTTGGCCAGATGTCTATGTCCAGGGCCATCAACCTAACCCAGAAACTCTGG
ACAGCAGGCATCACAGCAGAAATCATGTACGACTGGTCACAGTCCCAAGAGGAATTACAA
GAGTACTGCAGACATCATGAAATCACCTATGTGGCCCTTGTCTCGGATAAAGAAGGAAGC
CATGTCAAGGTTAAGTCTTTCGAGAAGGAAAGGCAGACAGAGAAGCGTGTGCTGGAGACT
GAACTTGTGGACCATGTACTGCAGAAACTGAGGACTAAAGTCACTGATGAAAGGAATGGC
AGAGAAGCTTCCGATAATCTTGCAGTGCAAAATCTGAAGGGGTCATTTTCTAATGCTTCA
GGTTTGTTTGAAATCCATGGAGCAACAGTGGTTCCCATTGTGAGTGTGCTAGCCCCGGAG
AAGCTGTCAGCCAGCACTAGGAGGCGCTATGAAACTCAGGTACAAACTCGACTTCAGACC
TCCCTTGCCAACTTACATCAGAAAAGCAGTGAAATTGAAATTCTGGCTGTGGATCTACCC
AAAGAAACAATATTACAGTTTTTATCATTAGAGTGGGATGCTGATGAACAGGCATTTAAC
ACAACTGTGAAGCAGCTGCTGTCACGCCTGCCAAAGCAAAGATACCTCAAATTAGTCTGT
GATGAAATTTATAACATCAAAGTAGAAAAAAAGGTGTCTGTGCTATTTCTGTACAGCTAT
AGAGATGACTACTACAGAATCTTATTTTAA
Chromosome Location
15
Locus
15q15.1
External Identifiers
ResourceLink
UniProtKB IDQ9P2K8
UniProtKB Entry NameE2AK4_HUMAN
HGNC IDHGNC:19687
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails