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Protein

eIF-2-alpha kinase GCN2

Gene

GCN2

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) on 'Ser-52' in response to low amino acid availability (PubMed:1739968, PubMed:7623840, PubMed:8798780, PubMed:9528799, PubMed:10983975, PubMed:17202131). Plays a role as an activator of the general amino acid control (GAAC) pathway required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/SUI2 either to a competitive inhibitor of 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 GCN4, and hence allowing GCN4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:2660141, PubMed:2188100, PubMed:1739968, PubMed:7621831, PubMed:7623840, PubMed:8798780, PubMed:10801780, PubMed:11350982, PubMed:24333428). Binds uncharged tRNAs (PubMed:7623840, PubMed:10983975).13 Publications
(orthologuous-specific) Binds to aminoacylated tRNA(Phe) less tightly than to deacylated tRNA(Phe) (PubMed:10983975). Binds to double-stranded RNA (PubMed:9430731).2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.5 Publications

Enzyme regulationi

The kinase activity is stimulated upon binding to uncharged tRNAs (PubMed:7623840).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei628 – 6281ATPPROSITE-ProRule annotation
Active sitei835 – 8351Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi605 – 6139ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • double-stranded RNA binding Source: UniProtKB
  • eukaryotic translation initiation factor 2alpha kinase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein self-association Source: UniProtKB
  • ribosomal large subunit binding Source: UniProtKB
  • ribosome binding Source: UniProtKB
  • translation initiation factor binding Source: UniProtKB
  • tRNA binding Source: UniProtKB

GO - Biological processi

  • cellular response to amino acid starvation Source: UniProtKB
  • cellular response to benomyl Source: UniProtKB
  • cellular response to histidine Source: UniProtKB
  • cellular response to hydrogen peroxide Source: UniProtKB
  • cellular stress response to acidic pH Source: UniProtKB
  • chronological cell aging Source: SGD
  • DNA damage checkpoint Source: SGD
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of cellular response to amino acid starvation Source: UniProtKB
  • positive regulation of translational initiation in response to starvation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of eIF2 alpha phosphorylation by amino acid starvation Source: UniProtKB
  • regulation of translational initiation Source: UniProtKB
  • translation Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Protein biosynthesis, Stress response, Translation regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding, RNA-binding, tRNA-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-29848-MONOMER.
ReactomeiR-SCE-381042. PERK regulates gene expression.

Names & Taxonomyi

Protein namesi
Recommended name:
eIF-2-alpha kinase GCN2By similarity (EC:2.7.11.15 Publications)
Alternative name(s):
General control non-derepressible protein 2Imported
Serine/threonine-protein kinase GCN2Curated
Gene namesi
Name:GCN2Imported
Synonyms:AAS1
Ordered Locus Names:YDR283C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome IV

Organism-specific databases

EuPathDBiFungiDB:YDR283C.
SGDiS000002691. GCN2.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

  • cytosolic ribosome Source: SGD
  • large ribosomal subunit Source: UniProtKB
  • polysomal ribosome Source: UniProtKB
  • small ribosomal subunit Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 741Y → A: Inhibits interaction with GCN1, eIF-2-alpha phosphorylation and fails to derepress GCN4 translation in amino acid-starved cells. 2 Publications
Mutagenesisi582 – 5821S → F: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi594 – 5941R → D: Inhibits autophosphorylation, eIF-2-alpha kinase activity and derepression of GCN4 translation. Restores eIF-2-alpha kinase activity and derepression of GCN4, but not autophosphorylation; when associated with R-598. 1 Publication
Mutagenesisi598 – 5981D → R: Inhibits autophosphorylation, eIF-2-alpha kinase activity and derepression of GCN4 translation. Restores eIF-2-alpha kinase activity and derepression of GCN4, but not autophosphorylation; when associated with D-594. 1 Publication
Mutagenesisi601 – 6011E → K: Increases the constitutive kinase activity in absence of amino acid starvation. 1 Publication
Mutagenesisi628 – 6281K → V or R: Inhibits autophosphorylation, eIF-2-alpha kinase activity and derepression of GCN4 translation in amino acid-starved cells. 6 Publications
Mutagenesisi629 – 6291K → A: Does not abolish derepression of GCN4 translation and amino acid bosynthetic genes in amino acid-starved cells. 1 Publication
Mutagenesisi716 – 7161F → S: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi788 – 7881M → V: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi794 – 7941R → G: Constitutively active allele, bypass the tRNA binding-requirement for kinase activity. 1 Publication
Mutagenesisi803 – 8031E → V: Increases tRNA binding and the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 2 Publications
Mutagenesisi821 – 8211E → K: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 2 Publications
Mutagenesisi835 – 8351D → N: Loss of function. 1 Publication
Mutagenesisi861 – 8611H → Y: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi882 – 8821T → A, E or D: Partially impairs kinase activity. 1 Publication
Mutagenesisi882 – 8821T → S: No effect. 1 Publication
Mutagenesisi887 – 8871T → A, E or D: Completely abolishes kinase activity. 1 Publication
Mutagenesisi887 – 8871T → S: Partially impairs kinase activity. 1 Publication
Mutagenesisi1080 – 10801V → A: Inhibits dimerization; when associated with A-1088 and A-1090. 1 Publication
Mutagenesisi1088 – 10881L → A: Inhibits dimerization; when associated with A-1080 and A-1090. 1 Publication
Mutagenesisi1090 – 10901L → A: Inhibits dimerization; when associated with A-1080 and A-1088. 1 Publication
Mutagenesisi1119 – 11191Y → L: Inhibits binding to uncharged tRNAs, decreases eIF-2-alpha kinase activity and derepression of GCN4 translation and amino acid bosynthetic genes in amino acid-starved cells; when associated with L-1120. 3 Publications
Mutagenesisi1120 – 11201R → L: Inhibits binding to uncharged tRNAs, decreases eIF-2-alpha kinase activity and derepression of GCN4 translation and amino acid bosynthetic genes in amino acid-starved cells; when associated with L-1119. 3 Publications
Mutagenesisi1134 – 11341F → L: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1138 – 11381D → N: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1197 – 11971A → G: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1308 – 13081H → Y: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1338 – 13381G → D: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1552 – 15565KKANK → LLANI: Fails to derepress of GCN4 translation and amino acid bosynthetic genes in amino acid-starved cells and does not inhibit autophosphorylation. 1 Publication
Mutagenesisi1552 – 15521K → L: Reduces interaction with TIF11, Inhibits binding to uncharged tRNAs, reduces autophosphorylation, eIF-2-alpha kinase activity and ribosome association, but not dimerization; when associated with I-1553 and I-1556. 2 Publications
Mutagenesisi1553 – 15531K → I: Reduces interaction with TIF11, Inhibits binding to uncharged tRNAs, reduces autophosphorylation, eIF-2-alpha kinase activity and ribosome association, but not dimerization; when associated with L-1552 and I-1556. 2 Publications
Mutagenesisi1556 – 15561K → I: Reduces interaction with TIF11, Inhibits binding to uncharged tRNAs, reduces autophosphorylation, eIF-2-alpha kinase activity and ribosome association, but not dimerization; when associated with L-1552 and I-1553. 2 Publications
Mutagenesisi1557 – 15571R → K: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1591 – 15911E → K: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 1 Publication
Mutagenesisi1606 – 16061E → K: Increases the constitutive kinase activity and induces derepression of GCN4 translation and amino acid bosynthetic genes in absence of amino acid starvation. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 16591659eIF-2-alpha kinase GCN2PRO_0000085963Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei761 – 7611PhosphoserineCombined sources
Modified residuei882 – 8821Phosphothreonine; by autocatalysis1 Publication
Modified residuei887 – 8871Phosphothreonine; by autocatalysis1 Publication

Post-translational modificationi

Autophosphorylated, autophosphorylation on Thr-882 and Thr-887 increases kinase activity.6 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP15442.
PeptideAtlasiP15442.

PTM databases

iPTMnetiP15442.

Interactioni

Subunit structurei

Homodimer; homodimerization is important for kinase activation by uncharged tRNAs (PubMed:9566889, PubMed:10983975, PubMed:11250908, PubMed:17202131, PubMed:15964839). Interacts (via N-terminal RWD domain) with GCN1 (via N- and C-terminus); this interaction stimulates GCN2 kinase activity in a GCN20-dependent manner in response to amino acid starvation (PubMed:10775272, PubMed:11101534, PubMed:10801780, PubMed:11350982, PubMed:21849502). Interacts (via N-terminus) with the GCN1-GCN20 complex on translating ribosomes in amino acid-starved cells; GCN1 may bind near the ribosomal A-site and promotes the transfer of uncharged tRNAs from the A-site to the tRNA-binding domain in GCN2 for its subsequent kinase activation, and hence allowing GCN4 translational activation and derepression of amino acid biosynthetic genes (PubMed:10775272, PubMed:11101534). Interacts (via C-terminus) with TIF11; this interaction is direct, occurs in amino acid-repleted cells, may be stabilzed in a ribosome-dependent manner, reduces GCN2-mediated eIF-2-alpha phosphorylation but not GCN2 autophosphorylation and is lost in amino acid-starved cells and by uncharged tRNAs (PubMed:21849502). Associates (via C-terminus) with ribosomes (PubMed:2038314, PubMed:9430731, PubMed:10983975, PubMed:22888004).13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HRR25P292955EBI-330,EBI-8536
NPR1P222112EBI-330,EBI-12207

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein self-association Source: UniProtKB
  • translation initiation factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi32336. 189 interactions.
DIPiDIP-2346N.
IntActiP15442. 24 interactions.
MINTiMINT-625588.

Structurei

Secondary structure

1
1659
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 63Combined sources
Helixi8 – 2316Combined sources
Beta strandi26 – 316Combined sources
Beta strandi37 – 404Combined sources
Beta strandi48 – 536Combined sources
Beta strandi63 – 697Combined sources
Beta strandi80 – 845Combined sources
Helixi92 – 10716Combined sources
Helixi114 – 13017Combined sources
Helixi594 – 5985Combined sources
Beta strandi599 – 6079Combined sources
Beta strandi609 – 61810Combined sources
Turni619 – 6213Combined sources
Beta strandi624 – 63310Combined sources
Helixi634 – 64714Combined sources
Beta strandi653 – 6553Combined sources
Beta strandi658 – 6647Combined sources
Beta strandi781 – 7899Combined sources
Helixi796 – 8027Combined sources
Helixi805 – 8073Combined sources
Helixi809 – 82820Combined sources
Helixi838 – 8403Combined sources
Beta strandi841 – 8433Combined sources
Beta strandi849 – 8513Combined sources
Helixi888 – 8903Combined sources
Helixi893 – 8964Combined sources
Helixi905 – 91915Combined sources
Helixi925 – 93612Combined sources
Turni948 – 9503Combined sources
Helixi952 – 96110Combined sources
Helixi966 – 9683Combined sources
Helixi972 – 9776Combined sources
Helixi986 – 99510Combined sources
Beta strandi1541 – 15433Combined sources
Beta strandi1551 – 15533Combined sources
Helixi1560 – 157718Combined sources
Beta strandi1582 – 15865Combined sources
Helixi1590 – 15989Combined sources
Beta strandi1601 – 16033Combined sources
Helixi1604 – 16129Combined sources
Helixi1615 – 16173Combined sources
Helixi1621 – 163616Combined sources
Beta strandi1641 – 16466Combined sources
Turni1647 – 16493Combined sources
Beta strandi1652 – 16565Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZXEX-ray2.60A/B/C/D/E/F594-997[»]
1ZY4X-ray1.95A/B594-997[»]
1ZY5X-ray2.00A/B594-997[»]
1ZYCX-ray3.00A/B/C/D594-997[»]
1ZYDX-ray2.75A/B594-997[»]
2YZ0NMR-A1-138[»]
4OTMX-ray1.95A/B1519-1659[»]
ProteinModelPortaliP15442.
SMRiP15442. Positions 1-138, 283-558, 594-700, 722-1024, 1033-1493, 1538-1659.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15442.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 128112RWDPROSITE-ProRule annotationAdd
BLAST
Domaini256 – 527272Protein kinase 1PROSITE-ProRule annotationAdd
BLAST
Domaini599 – 981383Protein kinase 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni999 – 1519521Histidyl-tRNA synthetase-likeAdd
BLAST

Domaini

The C-terminal domain negatively regulates kinase activity via an autoinhibitory association with the protein kinase and histidyl-tRNA synthetase-like domains in amino acid-repleted cells, that is counteracted by uncharged tRNAs in amino acid-starved cells (PubMed:7623840, PubMed:8798780, PubMed:10983975, PubMed:11250908). The C-terminal, histidyl-tRNA synthetase-like region and protein kinase domains are necessary for homodimer formation (PubMed:9566889, PubMed:10983975, PubMed:11250908). The C-terminal and protein kinase domains are necessary for ribosome association (PubMed:9566889, PubMed:10983975). The C-terminal and histidyl-tRNA synthetase-like regions are required for uncharged tRNAs binding in amino acid-starved cells (PubMed:7623840, PubMed:8798780, PubMed:9430731, PubMed:10983975).6 Publications

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.PROSITE-ProRule annotation
Contains 2 protein kinase domains.PROSITE-ProRule annotation
Contains 1 RWD domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00530000062984.
HOGENOMiHOG000172724.
InParanoidiP15442.
KOiK16196.
OMAiSIFRRHG.
OrthoDBiEOG7F2527.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR016255. Gcn2.
IPR024435. HisRS-related_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR006575. RWD-domain.
IPR008271. Ser/Thr_kinase_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF12745. HGTP_anticodon2. 1 hit.
PF00069. Pkinase. 3 hits.
PF05773. RWD. 1 hit.
[Graphical view]
PIRSFiPIRSF000660. Ser/Thr_PK_GCN2. 1 hit.
SMARTiSM00591. RWD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
SSF56112. SSF56112. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50908. RWD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P15442-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLSHLTLDQ YYEIQCNELE AIRSIYMDDF TDLTKRKSSW DKQPQIIFEI
60 70 80 90 100
TLRSVDKEPV ESSITLHFAM TPMYPYTAPE IEFKNVQNVM DSQLQMLKSE
110 120 130 140 150
FKKIHNTSRG QEIIFEITSF TQEKLDEFQN VVNTQSLEDD RLQRIKETKE
160 170 180 190 200
QLEKEEREKQ QETIKKRSDE QRRIDEIVQR ELEKRQDDDD DLLFNRTTQL
210 220 230 240 250
DLQPPSEWVA SGEAIVFSKT IKAKLPNNSM FKFKAVVNPK PIKLTSDIFS
260 270 280 290 300
FSKQFLVKPY IPPESPLADF LMSSEMMENF YYLLSEIELD NSYFNTSNGK
310 320 330 340 350
KEIANLEKEL ETVLKAKHDN VNRLFGYTVE RMGRNNATFV WKIRLLTEYC
360 370 380 390 400
NYYPLGDLIQ SVGFVNLATA RIWMIRLLEG LEAIHKLGIV HKCINLETVI
410 420 430 440 450
LVKDADFGST IPKLVHSTYG YTVLNMLSRY PNKNGSSVEL SPSTWIAPEL
460 470 480 490 500
LKFNNAKPQR LTDIWQLGVL FIQIISGSDI VMNFETPQEF LDSTSMDETL
510 520 530 540 550
YDLLSKMLNN DPKKRLGTLE LLPMKFLRTN IDSTINRFNL VSESVNSNSL
560 570 580 590 600
ELTPGDTITV RGNGGRTLSQ SSIRRRSFNV GSRFSSINPA TRSRYASDFE
610 620 630 640 650
EIAVLGQGAF GQVVKARNAL DSRYYAIKKI RHTEEKLSTI LSEVMLLASL
660 670 680 690 700
NHQYVVRYYA AWLEEDSMDE NVFESTDEES DLSESSSDFE ENDLLDQSSI
710 720 730 740 750
FKNRTNHDLD NSNWDFISGS GYPDIVFENS SRDDENEDLD HDTSSTSSSE
760 770 780 790 800
SQDDTDKESK SIQNVPRRRN FVKPMTAVKK KSTLFIQMEY CENRTLYDLI
810 820 830 840 850
HSENLNQQRD EYWRLFRQIL EALSYIHSQG IIHRDLKPMN IFIDESRNVK
860 870 880 890 900
IGDFGLAKNV HRSLDILKLD SQNLPGSSDN LTSAIGTAMY VATEVLDGTG
910 920 930 940 950
HYNEKIDMYS LGIIFFEMIY PFSTGMERVN ILKKLRSVSI EFPPDFDDNK
960 970 980 990 1000
MKVEKKIIRL LIDHDPNKRP GARTLLNSGW LPVKHQDEVI KEALKSLSNP
1010 1020 1030 1040 1050
SSPWQQQVRE SLFNQSYSLT NDILFDNSVP TSTPFANILR SQMTEEVVKI
1060 1070 1080 1090 1100
FRKHGGIENN APPRIFPKAP IYGTQNVYEV LDKGGTVLQL QYDLTYPMAR
1110 1120 1130 1140 1150
YLSKNPSLIS KQYRMQHVYR PPDHSRSSLE PRKFGEIDFD IISKSSSESG
1160 1170 1180 1190 1200
FYDAESLKII DEILTVFPVF EKTNTFFILN HADILESVFN FTNIDKAQRP
1210 1220 1230 1240 1250
LVSRMLSQVG FARSFKEVKN ELKAQLNISS TALNDLELFD FRLDFEAAKK
1260 1270 1280 1290 1300
RLYKLMIDSP HLKKIEDSLS HISKVLSYLK PLEVARNVVI SPLSNYNSAF
1310 1320 1330 1340 1350
YKGGIMFHAV YDDGSSRNMI AAGGRYDTLI SFFARPSGKK SSNTRKAVGF
1360 1370 1380 1390 1400
NLAWETIFGI AQNYFKLASG NRIKKRNRFL KDTAVDWKPS RCDVLISSFS
1410 1420 1430 1440 1450
NSLLDTIGVT ILNTLWKQNI KADMLRDCSS VDDVVTGAQQ DGIDWILLIK
1460 1470 1480 1490 1500
QQAYPLTNHK RKYKPLKIKK LSTNVDIDLD LDEFLTLYQQ ETGNKSLIND
1510 1520 1530 1540 1550
SLTLGDKADE FKRWDENSSA GSSQEGDIDD VVAGSTNNQK VIYVPNMATR
1560 1570 1580 1590 1600
SKKANKREKW VYEDAARNSS NMILHNLSNA PIITVDALRD ETLEIISITS
1610 1620 1630 1640 1650
LAQKEEWLRK VFGSGNNSTP RSFATSIYNN LSKEAHKGNR WAILYCHKTG

KSSVIDLQR
Length:1,659
Mass (Da):190,193
Last modified:September 5, 2006 - v3
Checksum:i1F56E4B046D52325
GO

Sequence cautioni

The sequence AAA34636.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAA34881.1 differs from that shown. Reason: Frameshift at positions 71, 218, 226, 271, 279, 370, 389, 432, 592, 605, 1052, 1125, 1197, 1255, 1331 and 1428. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti70 – 701M → I in AAA34881 (PubMed:3290651).Curated
Sequence conflicti220 – 2267TIKAKLP → NYKGKIA in AAA34881 (PubMed:3290651).Curated
Sequence conflicti271 – 2799LMSSEMMEN → YVFSNHGKS in AAA34881 (PubMed:3290651).Curated
Sequence conflicti374 – 3741M → I in AAA34881 (PubMed:3290651).Curated
Sequence conflicti392 – 3921K → Q in AAA34881 (PubMed:3290651).Curated
Sequence conflicti395 – 3951N → S in AAA34881 (PubMed:3290651).Curated
Sequence conflicti407 – 4071F → C in AAA34881 (PubMed:3290651).Curated
Sequence conflicti411 – 4133IPK → MPE in AAA34881 (PubMed:3290651).Curated
Sequence conflicti475 – 4751I → M in AAA34881 (PubMed:3290651).Curated
Sequence conflicti589 – 5891P → A in AAA34881 (PubMed:3290651).Curated
Sequence conflicti604 – 6052VL → FS in AAA34881 (PubMed:3290651).Curated
Sequence conflicti622 – 6221S → T in AAA34881 (PubMed:3290651).Curated
Sequence conflicti640 – 6412IL → MI in AAA34881 (PubMed:3290651).Curated
Sequence conflicti727 – 7271F → C in AAA34881 (PubMed:3290651).Curated
Sequence conflicti839 – 8391M → K in AAA34881 (PubMed:3290651).Curated
Sequence conflicti954 – 9541E → Q in AAA34881 (PubMed:3290651).Curated
Sequence conflicti1144 – 11441K → E in AAA34881 (PubMed:3290651).Curated
Sequence conflicti1328 – 13314TLIS → RFHT in AAA34881 (PubMed:3290651).Curated
Sequence conflicti1348 – 13481V → A in AAA34881 (PubMed:3290651).Curated
Sequence conflicti1356 – 13561T → I in AAA34881 (PubMed:3290651).Curated
Sequence conflicti1434 – 14341V → I in AAA34881 (PubMed:3290651).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27082 Genomic DNA. Translation: AAA34636.1. Different initiation.
U51030 Genomic DNA. Translation: AAB64461.1.
M20487 Genomic DNA. Translation: AAA34881.1. Sequence problems.
BK006938 Genomic DNA. Translation: DAA12123.1.
PIRiS70139. OKBYN2.
RefSeqiNP_010569.3. NM_001180591.3.

Genome annotation databases

EnsemblFungiiYDR283C; YDR283C; YDR283C.
GeneIDi851877.
KEGGisce:YDR283C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27082 Genomic DNA. Translation: AAA34636.1. Different initiation.
U51030 Genomic DNA. Translation: AAB64461.1.
M20487 Genomic DNA. Translation: AAA34881.1. Sequence problems.
BK006938 Genomic DNA. Translation: DAA12123.1.
PIRiS70139. OKBYN2.
RefSeqiNP_010569.3. NM_001180591.3.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZXEX-ray2.60A/B/C/D/E/F594-997[»]
1ZY4X-ray1.95A/B594-997[»]
1ZY5X-ray2.00A/B594-997[»]
1ZYCX-ray3.00A/B/C/D594-997[»]
1ZYDX-ray2.75A/B594-997[»]
2YZ0NMR-A1-138[»]
4OTMX-ray1.95A/B1519-1659[»]
ProteinModelPortaliP15442.
SMRiP15442. Positions 1-138, 283-558, 594-700, 722-1024, 1033-1493, 1538-1659.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32336. 189 interactions.
DIPiDIP-2346N.
IntActiP15442. 24 interactions.
MINTiMINT-625588.

PTM databases

iPTMnetiP15442.

Proteomic databases

MaxQBiP15442.
PeptideAtlasiP15442.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYDR283C; YDR283C; YDR283C.
GeneIDi851877.
KEGGisce:YDR283C.

Organism-specific databases

EuPathDBiFungiDB:YDR283C.
SGDiS000002691. GCN2.

Phylogenomic databases

GeneTreeiENSGT00530000062984.
HOGENOMiHOG000172724.
InParanoidiP15442.
KOiK16196.
OMAiSIFRRHG.
OrthoDBiEOG7F2527.

Enzyme and pathway databases

BioCyciYEAST:G3O-29848-MONOMER.
ReactomeiR-SCE-381042. PERK regulates gene expression.

Miscellaneous databases

EvolutionaryTraceiP15442.
PROiP15442.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR016255. Gcn2.
IPR024435. HisRS-related_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR006575. RWD-domain.
IPR008271. Ser/Thr_kinase_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF12745. HGTP_anticodon2. 1 hit.
PF00069. Pkinase. 3 hits.
PF05773. RWD. 1 hit.
[Graphical view]
PIRSFiPIRSF000660. Ser/Thr_PK_GCN2. 1 hit.
SMARTiSM00591. RWD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
SSF56112. SSF56112. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50908. RWD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability."
    Wek R.C., Jackson B.M., Hinnebusch A.G.
    Proc. Natl. Acad. Sci. U.S.A. 86:4579-4583(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, MUTAGENESIS OF LYS-628 AND LYS-629.
  2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."
    Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T.
    , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P.
    Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  4. "Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase."
    Roussou I., Thireos G., Hauge B.M.
    Mol. Cell. Biol. 8:2132-2139(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1481.
    Strain: ATCC 204508 / S288c.
  5. "Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression."
    Wek R.C., Ramirez M., Jackson B.M., Hinnebusch A.G.
    Mol. Cell. Biol. 10:2820-2831(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF GLU-601; LYS-628; GLU-821 AND GLU-1606.
  6. "Ribosome association of GCN2 protein kinase, a translational activator of the GCN4 gene of Saccharomyces cerevisiae."
    Ramirez M., Wek R.C., Hinnebusch A.G.
    Mol. Cell. Biol. 11:3027-3036(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH RIBOSOMES, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
  7. "Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast."
    Dever T.E., Feng L., Wek R.C., Cigan A.M., Donahue T.F., Hinnebusch A.G.
    Cell 68:585-596(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF LYS-628.
  8. "Mutations activating the yeast eIF-2 alpha kinase GCN2: isolation of alleles altering the domain related to histidyl-tRNA synthetases."
    Ramirez M., Wek R.C., Vazquez de Aldana C.R., Jackson B.M., Freeman B., Hinnebusch A.G.
    Mol. Cell. Biol. 12:5801-5815(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-582; PHE-716; MET-788; GLU-803; GLU-821; HIS-861; PHE-1134; ASP-1138; ALA-1197; HIS-1308; GLY-1338; ARG-1557; GLU-1591 AND GLU-1606.
  9. "GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex that mediates activation of the eIF-2 alpha kinase GCN2 in amino acid-starved cells."
    Vazquez de Aldana C.R., Marton M.J., Hinnebusch A.G.
    EMBO J. 14:3184-3199(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids."
    Wek S.A., Zhu S., Wek R.C.
    Mol. Cell. Biol. 15:4497-4506(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, TRNA-BINDING, DOMAIN, MUTAGENESIS OF TYR-1119 AND ARG-1120.
  11. "Histidyl-tRNA synthetase-related sequences in GCN2 protein kinase regulate in vitro phosphorylation of eIF-2."
    Zhu S., Sobolev A.Y., Wek R.C.
    J. Biol. Chem. 271:24989-24994(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, DOMAIN, MUTAGENESIS OF LYS-628; TYR-1119 AND ARG-1120.
  12. "Ribosome-binding domain of eukaryotic initiation factor-2 kinase GCN2 facilitates translation control."
    Zhu S., Wek R.C.
    J. Biol. Chem. 273:1808-1814(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ASSOCIATION WITH RIBOSOMES, DOMAIN, MUTAGENESIS OF TYR-1119; ARG-1120 AND 1552-LYS--LYS-1556.
  13. "Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2."
    Romano P.R., Garcia-Barrio M.T., Zhang X., Wang Q., Taylor D.R., Zhang F., Herring C., Mathews M.B., Qin J., Hinnebusch A.G.
    Mol. Cell. Biol. 18:2282-2297(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, AUTOPHOSPHORYLATION AT THR-882 AND THR-887, MUTAGENESIS OF THR-882 AND THR-887.
  14. "Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosome-binding region and the protein kinase domain."
    Qiu H., Garcia-Barrio M.T., Hinnebusch A.G.
    Mol. Cell. Biol. 18:2697-2711(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, DOMAIN.
  15. "Association of GCN1-GCN20 regulatory complex with the N-terminus of eIF2alpha kinase GCN2 is required for GCN2 activation."
    Garcia-Barrio M., Dong J., Ufano S., Hinnebusch A.G.
    EMBO J. 19:1887-1899(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GCN1, IDENTIFICATION IN A COMPLEX WITH GCN1 AND GCN20.
  16. "Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells."
    Sattlegger E., Hinnebusch A.G.
    EMBO J. 19:6622-6633(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GCN1, IDENTIFICATION IN A COMPLEX WITH GCN1 AND GCN20.
  17. "GI domain-mediated association of the eukaryotic initiation factor 2alpha kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast."
    Kubota H., Sakaki Y., Ito T.
    J. Biol. Chem. 275:20243-20246(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GCN1, MUTAGENESIS OF TYR-74.
  18. "Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain."
    Dong J., Qiu H., Garcia-Barrio M., Anderson J., Hinnebusch A.G.
    Mol. Cell 6:269-279(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TRNA-BINDING, ASSOCIATION WITH RIBOSOMES, AUTOPHOSPHORYLATION, DOMAIN, MUTAGENESIS OF LYS-628; GLU-803; TYR-1119; ARG-1120; LYS-1552; LYS-1553 AND LYS-1556.
  19. "The tRNA-binding moiety in GCN2 contains a dimerization domain that interacts with the kinase domain and is required for tRNA binding and kinase activation."
    Qiu H., Dong J., Hu C., Francklyn C.S., Hinnebusch A.G.
    EMBO J. 20:1425-1438(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, DOMAIN, MUTAGENESIS OF VAL-1080; LEU-1088 AND LEU-1090.
  20. "Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase GCN2."
    Kubota H., Ota K., Sakaki Y., Ito T.
    J. Biol. Chem. 276:17591-17596(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GCN1, MUTAGENESIS OF TYR-74.
  21. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  22. "Conserved intermolecular salt bridge required for activation of protein kinases PKR, GCN2, and PERK."
    Dey M., Cao C., Sicheri F., Dever T.E.
    J. Biol. Chem. 282:6653-6660(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AUTOPHOSPHORYLATION, MUTAGENESIS OF ARG-594; ASP-598 AND LYS-628.
  23. "Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry."
    Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.
    Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-761, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  24. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
    Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
    Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  25. "Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity."
    Visweswaraiah J., Lageix S., Castilho B.A., Izotova L., Kinzy T.G., Hinnebusch A.G., Sattlegger E.
    J. Biol. Chem. 286:36568-36579(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GCN1 AND TIF11, MUTAGENESIS OF LYS-1552; LYS-1553 AND LYS-1556.
  26. "Overexpression of eukaryotic translation elongation factor 3 impairs Gcn2 protein activation."
    Visweswaraiah J., Lee S.J., Hinnebusch A.G., Sattlegger E.
    J. Biol. Chem. 287:37757-37768(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH RIBOSOMES.
  27. "Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2."
    Cambiaghi T.D., Pereira C.M., Shanmugam R., Bolech M., Wek R.C., Sattlegger E., Castilho B.A.
    Biochem. Biophys. Res. Commun. 443:592-597(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  28. "Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2alpha protein kinase GCN2."
    Padyana A.K., Qiu H., Roll-Mecak A., Hinnebusch A.G., Burley S.K.
    J. Biol. Chem. 280:29289-29299(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 594-664 AND 768-997 OF WILD-TYPE AND MUTANTS GLY-794 AND ASN-835 IN COMPLEX WITH ATP, SUBUNIT.

Entry informationi

Entry nameiGCN2_YEAST
AccessioniPrimary (citable) accession number: P15442
Secondary accession number(s): D6VSR3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: September 5, 2006
Last modified: June 8, 2016
This is version 186 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 279 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome IV
    Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.