P15442

EV
Gene name
GCN2
Protein name
eIF-2-alpha kinase GCN2
Names
General control non-derepressible protein 2, Serine/threonine-protein kinase GCN2
Species
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
KEGG Pathway
sce:YDR283C
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class
EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED (PTHR11042)

Descriptions

GCN2 is an activator of the general amino acid control (GAAC) pathway initiated for adaptation to nutrient starvation via phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF-2). The binding region of substrate eIF2 is prevented by binding of the C-terminus to the PK domain, and possibly also by HisRS-N-PK (protein kinase) interaction. Under starvation conditions, uncharged tRNA binds to GCN2 producing conformational changes in both domains that are transmitted to the PK domain, consequently releasing the substrate-binding cleft in the PK domain and allows eIF2 binding and phosphorylation.

Autoinhibitory domains (AIDs)

1498-1659 (C-terminal domain) EV

Target domain

750-999 (PK domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment, Structural analysis

Accessory elements

852-889 (Activation loop from InterPro)

Target domain

599-981 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

8 structures for P15442

Entry ID Method Resolution Chain Position Source
1ZXE X-ray 260 A A/B/C/D/E/F 594-997 PDB
1ZY4 X-ray 195 A A/B 594-997 PDB
1ZY5 X-ray 200 A A/B 594-997 PDB
1ZYC X-ray 300 A A/B/C/D 594-997 PDB
1ZYD X-ray 275 A A/B 594-997 PDB
2YZ0 NMR - A 1-138 PDB
4OTM X-ray 195 A A/B 1519-1659 PDB
AF-P15442-F1 Predicted AlphaFoldDB

13 variants for P15442

Variant ID(s) Position Change Description Diseaes Association Provenance
s04-1029985 21 A>T No SGRP
s04-1029697 117 I>V No SGRP
s04-1029304 248 I>V No SGRP
s04-1029099 316 A>V No SGRP
s04-1029094 318 H>Y No SGRP
s04-1028505 514 K>R No SGRP
s04-1028046 667 S>N No SGRP
s04-1027792 752 Q>E No SGRP
s04-1027227 940 I>T No SGRP
s04-1026532 1172 K>E No SGRP
s04-1025934 1371 N>S No SGRP
s04-1025319 1576 N>S No SGRP
s04-1025191 1619 T>A No SGRP

No associated diseases with P15442

2 regional properties for P15442

Type Name Position InterPro Accession
domain Nuclear hormone receptor, ligand-binding domain 679 - 913 IPR000536
domain Zinc finger, nuclear hormone receptor-type 564 - 639 IPR001628

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
PANTHER Family PTHR11042 EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED
PANTHER Subfamily PTHR11042:SF136 EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE 1
PANTHER Protein Class non-receptor serine/threonine protein kinase
protein modifying enzyme
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
cytosolic ribosome A ribosome located in the cytosol.
large ribosomal subunit The larger of the two subunits of a ribosome. Two sites on the ribosomal large subunit are involved in translation, namely the aminoacyl site (A site) and peptidyl site (P site).
polysomal ribosome A ribosome bound to mRNA that forms part of a polysome.
small ribosomal subunit The smaller of the two subunits of a ribosome.

13 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
double-stranded RNA binding Binding to double-stranded RNA.
eukaryotic translation initiation factor 2alpha kinase activity Catalysis of the reaction: ATP
protein homodimerization activity +Binding to an identical protein to form a homodimer.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein kinase inhibitor activity Binds to and stops, prevents or reduces the activity of a protein kinase, an enzyme which phosphorylates a protein.
protein self-association Binding to a domain within the same polypeptide.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
ribosomal large subunit binding Binding to a large ribosomal subunit.
ribosome binding Binding to a ribosome.
translation initiation factor binding Binding to a translation initiation factor, any polypeptide factor involved in the initiation of ribosome-mediated translation.
tRNA binding Binding to a transfer RNA.

17 GO annotations of biological process

Name Definition
cellular response to amino acid starvation Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of amino acids.
cellular response to benomyl Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a benomyl stimulus.
cellular response to histidine Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a histidine stimulus.
cellular response to hydrogen peroxide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
cellular stress response to acidic pH Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a disturbance in the homeostasis of organismal or cellular pH (with pH < 7). pH is a measure of the acidity or basicity of an aqueous solution.
DNA damage checkpoint signaling A signal transduction process that contributes to a DNA damage checkpoint.
GCN2-mediated signaling A series of reactions in which a signal is passed on to downstream proteins within the cell via GCN2 (also known as EIF2AK4), an intracellular protein kinase that is activated by stress signals, such as amino acid starvation.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of protein kinase activity by protein phosphorylation Any protein phosphorylation process that negatively regulates protein kinase activity.
negative regulation of TORC1 signaling Any process that stops, prevents or reduces the frequency, rate or extent of TORC1 signaling.
positive regulation of cellular response to amino acid starvation Any process that activates or increases the frequency, rate or extent of cellular response to amino acid starvation.
positive regulation of macroautophagy Any process, such as recognition of nutrient depletion, that activates or increases the rate of macroautophagy to bring cytosolic macromolecules to the vacuole/lysosome for degradation.
positive regulation of translational initiation in response to starvation Any process that activates or increases the frequency, rate or extent of translation initiation, as a result of deprivation of nourishment.
protein autophosphorylation The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of translational initiation Any process that modulates the frequency, rate or extent of translational initiation.
translation The cellular metabolic process in which a protein is formed, using the sequence of a mature mRNA or circRNA molecule to specify the sequence of amino acids in a polypeptide chain. Translation is mediated by the ribosome, and begins with the formation of a ternary complex between aminoacylated initiator methionine tRNA, GTP, and initiation factor 2, which subsequently associates with the small subunit of the ribosome and an mRNA or circRNA. Translation ends with the release of a polypeptide chain from the ribosome.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P32944 SWE1 Mitosis inhibitor protein kinase SWE1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q9P2K8 EIF2AK4 eIF-2-alpha kinase GCN2 Homo sapiens (Human) EV
Q9QZ05 Eif2ak4 eIF-2-alpha kinase GCN2 Mus musculus (Mouse) EV SS
D4A7V9 Eif2ak4 eIF-2-alpha kinase GCN2 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MSLSHLTLDQ YYEIQCNELE AIRSIYMDDF TDLTKRKSSW DKQPQIIFEI TLRSVDKEPV
70 80 90 100 110 120
ESSITLHFAM TPMYPYTAPE IEFKNVQNVM DSQLQMLKSE FKKIHNTSRG QEIIFEITSF
130 140 150 160 170 180
TQEKLDEFQN VVNTQSLEDD RLQRIKETKE QLEKEEREKQ QETIKKRSDE QRRIDEIVQR
190 200 210 220 230 240
ELEKRQDDDD DLLFNRTTQL DLQPPSEWVA SGEAIVFSKT IKAKLPNNSM FKFKAVVNPK
250 260 270 280 290 300
PIKLTSDIFS FSKQFLVKPY IPPESPLADF LMSSEMMENF YYLLSEIELD NSYFNTSNGK
310 320 330 340 350 360
KEIANLEKEL ETVLKAKHDN VNRLFGYTVE RMGRNNATFV WKIRLLTEYC NYYPLGDLIQ
370 380 390 400 410 420
SVGFVNLATA RIWMIRLLEG LEAIHKLGIV HKCINLETVI LVKDADFGST IPKLVHSTYG
430 440 450 460 470 480
YTVLNMLSRY PNKNGSSVEL SPSTWIAPEL LKFNNAKPQR LTDIWQLGVL FIQIISGSDI
490 500 510 520 530 540
VMNFETPQEF LDSTSMDETL YDLLSKMLNN DPKKRLGTLE LLPMKFLRTN IDSTINRFNL
550 560 570 580 590 600
VSESVNSNSL ELTPGDTITV RGNGGRTLSQ SSIRRRSFNV GSRFSSINPA TRSRYASDFE
610 620 630 640 650 660
EIAVLGQGAF GQVVKARNAL DSRYYAIKKI RHTEEKLSTI LSEVMLLASL NHQYVVRYYA
670 680 690 700 710 720
AWLEEDSMDE NVFESTDEES DLSESSSDFE ENDLLDQSSI FKNRTNHDLD NSNWDFISGS
730 740 750 760 770 780
GYPDIVFENS SRDDENEDLD HDTSSTSSSE SQDDTDKESK SIQNVPRRRN FVKPMTAVKK
790 800 810 820 830 840
KSTLFIQMEY CENRTLYDLI HSENLNQQRD EYWRLFRQIL EALSYIHSQG IIHRDLKPMN
850 860 870 880 890 900
IFIDESRNVK IGDFGLAKNV HRSLDILKLD SQNLPGSSDN LTSAIGTAMY VATEVLDGTG
910 920 930 940 950 960
HYNEKIDMYS LGIIFFEMIY PFSTGMERVN ILKKLRSVSI EFPPDFDDNK MKVEKKIIRL
970 980 990 1000 1010 1020
LIDHDPNKRP GARTLLNSGW LPVKHQDEVI KEALKSLSNP SSPWQQQVRE SLFNQSYSLT
1030 1040 1050 1060 1070 1080
NDILFDNSVP TSTPFANILR SQMTEEVVKI FRKHGGIENN APPRIFPKAP IYGTQNVYEV
1090 1100 1110 1120 1130 1140
LDKGGTVLQL QYDLTYPMAR YLSKNPSLIS KQYRMQHVYR PPDHSRSSLE PRKFGEIDFD
1150 1160 1170 1180 1190 1200
IISKSSSESG FYDAESLKII DEILTVFPVF EKTNTFFILN HADILESVFN FTNIDKAQRP
1210 1220 1230 1240 1250 1260
LVSRMLSQVG FARSFKEVKN ELKAQLNISS TALNDLELFD FRLDFEAAKK RLYKLMIDSP
1270 1280 1290 1300 1310 1320
HLKKIEDSLS HISKVLSYLK PLEVARNVVI SPLSNYNSAF YKGGIMFHAV YDDGSSRNMI
1330 1340 1350 1360 1370 1380
AAGGRYDTLI SFFARPSGKK SSNTRKAVGF NLAWETIFGI AQNYFKLASG NRIKKRNRFL
1390 1400 1410 1420 1430 1440
KDTAVDWKPS RCDVLISSFS NSLLDTIGVT ILNTLWKQNI KADMLRDCSS VDDVVTGAQQ
1450 1460 1470 1480 1490 1500
DGIDWILLIK QQAYPLTNHK RKYKPLKIKK LSTNVDIDLD LDEFLTLYQQ ETGNKSLIND
1510 1520 1530 1540 1550 1560
SLTLGDKADE FKRWDENSSA GSSQEGDIDD VVAGSTNNQK VIYVPNMATR SKKANKREKW
1570 1580 1590 1600 1610 1620
VYEDAARNSS NMILHNLSNA PIITVDALRD ETLEIISITS LAQKEEWLRK VFGSGNNSTP
1630 1640 1650
RSFATSIYNN LSKEAHKGNR WAILYCHKTG KSSVIDLQR