E2AKB_CAEEL
ID E2AKB_CAEEL Reviewed; 1699 AA.
AC D0Z5N4; Q9XVY4;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase gcn-2 {ECO:0000305|PubMed:22719267};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q19192};
DE AltName: Full=General control nonderepressible kinase 2 {ECO:0000312|WormBase:Y81G3A.3b};
GN Name=gcn-2 {ECO:0000312|WormBase:Y81G3A.3b};
GN ORFNames=Y81G3A.3 {ECO:0000312|WormBase:Y81G3A.3b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION.
RX PubMed=20733002; DOI=10.1128/mcb.00922-10;
RA Mao X.R., Crowder C.M.;
RT "Protein misfolding induces hypoxic preconditioning via a subset of the
RT unfolded protein response machinery.";
RL Mol. Cell. Biol. 30:5033-5042(2010).
RN [3] {ECO:0000305}
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23076791; DOI=10.1152/ajpcell.00294.2012;
RA Lee E.C., Strange K.;
RT "GCN-2 dependent inhibition of protein synthesis activates osmosensitive
RT gene transcription via WNK and Ste20 kinase signaling.";
RL Am. J. Physiol. 303:C1269-1277(2012).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22719267; DOI=10.1371/journal.pgen.1002760;
RA Baker B.M., Nargund A.M., Sun T., Haynes C.M.;
RT "Protective coupling of mitochondrial function and protein synthesis via
RT the eIF2alpha kinase GCN-2.";
RL PLoS Genet. 8:E1002760-E1002760(2012).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=23692540; DOI=10.1111/acel.12101;
RA Rousakis A., Vlassis A., Vlanti A., Patera S., Thireos G., Syntichaki P.;
RT "The general control nonderepressible-2 kinase mediates stress response and
RT longevity induced by target of rapamycin inactivation in Caenorhabditis
RT elegans.";
RL Aging Cell 12:742-751(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which phosphorylates the
CC alpha subunit of eukaryotic translation-initiation factor 2
CC (eIF2alpha), leading to its inactivation and thus to a rapid reduction
CC of translational initiation and repression of global protein synthesis
CC (By similarity). Involved in the unfolded protein response (UPR)
CC triggered by several stresses including mitochondrial, osmotic and
CC oxidative stresses, amino acid deprivation and UV irradiation, probably
CC by phosphorylating and inhibiting eIF2alpha (PubMed:20733002,
CC PubMed:23076791, PubMed:22719267, PubMed:23692540). In addition, leads
CC to the selective translation/transcription of some mRNA including atf-
CC 5, pha-4 and gpdh-1 which are part of the UPR (PubMed:23076791,
CC PubMed:23692540). Required for maintaining lifespan during amino acid
CC starvation (PubMed:23692540). Involved in hypoxia-mediated adaptive
CC protective response (PubMed:20733002). {ECO:0000250|UniProtKB:Q19192,
CC ECO:0000269|PubMed:20733002, ECO:0000269|PubMed:22719267,
CC ECO:0000269|PubMed:23076791, ECO:0000269|PubMed:23692540}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q19192};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q19192};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:Y81G3A.3b};
CC IsoId=D0Z5N4-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y81G3A.3a};
CC IsoId=D0Z5N4-2; Sequence=VSP_057682;
CC -!- DOMAIN: The protein kinase domain 1 is predicted to be catalytically
CC inactive. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in slower
CC development and shortened lifespan when exposed to mitochondrial
CC stress. {ECO:0000269|PubMed:22719267}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. GCN2 subfamily. {ECO:0000305}.
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DR EMBL; BX284602; CBI63247.2; -; Genomic_DNA.
DR EMBL; BX284602; CAA22515.2; -; Genomic_DNA.
DR PIR; T27447; T27447.
DR RefSeq; NP_001254370.2; NM_001267441.2.
DR RefSeq; NP_001254371.2; NM_001267442.2.
DR AlphaFoldDB; D0Z5N4; -.
DR SMR; D0Z5N4; -.
DR DIP; DIP-27197N; -.
DR IntAct; D0Z5N4; 1.
DR STRING; 6239.Y81G3A.3b; -.
DR EPD; D0Z5N4; -.
DR PaxDb; D0Z5N4; -.
DR PeptideAtlas; D0Z5N4; -.
DR PRIDE; D0Z5N4; -.
DR EnsemblMetazoa; Y81G3A.3a.1; Y81G3A.3a.1; WBGene00013591. [D0Z5N4-2]
DR EnsemblMetazoa; Y81G3A.3b.1; Y81G3A.3b.1; WBGene00013591. [D0Z5N4-1]
DR UCSC; Y81G3A.3; c. elegans.
DR WormBase; Y81G3A.3a; CE47938; WBGene00013591; gcn-2. [D0Z5N4-2]
DR WormBase; Y81G3A.3b; CE47891; WBGene00013591; gcn-2. [D0Z5N4-1]
DR eggNOG; KOG1035; Eukaryota.
DR InParanoid; D0Z5N4; -.
DR OMA; ISEWTFR; -.
DR OrthoDB; 64059at2759; -.
DR PhylomeDB; D0Z5N4; -.
DR PRO; PR:D0Z5N4; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00013591; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0019725; P:cellular homeostasis; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:UniProtKB.
DR GO; GO:0034514; P:mitochondrial unfolded protein response; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0061063; P:positive regulation of nematode larval development; IMP:UniProtKB.
DR GO; GO:1904808; P:positive regulation of protein oxidation; IGI:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0060378; P:regulation of brood size; IGI:UniProtKB.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR GO; GO:0009408; P:response to heat; IMP:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IMP:UniProtKB.
DR GO; GO:1903935; P:response to sodium arsenite; IGI:UniProtKB.
DR GO; GO:0042594; P:response to starvation; IMP:UniProtKB.
DR GO; GO:0009411; P:response to UV; IMP:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IMP:WormBase.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR041715; HisRS-like_core.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00069; Pkinase; 2.
DR Pfam; PF05773; RWD; 1.
DR Pfam; PF13393; tRNA-synt_His; 1.
DR SMART; SM00591; RWD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50908; RWD; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Stress response; Transferase; Translation regulation;
KW Unfolded protein response.
FT CHAIN 1..1699
FT /note="Eukaryotic translation initiation factor 2-alpha
FT kinase gcn-2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433217"
FT DOMAIN 22..138
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT DOMAIN 108..507
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 508..999
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 572..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..708
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 829
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 114..122
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 497..505
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 520
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1552..1554
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_057682"
SQ SEQUENCE 1699 AA; 191260 MW; 6C68AC5637EE4639 CRC64;
MTKENQIVLD ERVKENQHLQ EEEKLALDAV YLNQITYIKA HWHVWVPTNC HILLKALDSC
FLNGDPLGKS KLSVILHVKC SEDYPQRKPA VDLLDPQGLS KEDVQNLLTI LRQMADTWEG
CVVIAELAHR VREFLTDHTP RPAGSFHDDM LANKVRTEAE KQRKRLDTEQ KELELLEEEM
RQRNAIEMEK TLNGTRQENE TRIIGGRRIV VLSNMPNTQL LISEWTFRFS SNRNPAEGKR
KDFAPFLQKL DAVYNEIQKL CEIKGLDQNL VEYAFVHLQK ISVSPDQILI QLNVAQKIFS
SEENMQDTYE LIVQKSNLLR LLAAQAICGL RYLHEASMTH KHLTLGSVWT RNSTGDCVFR
FSDFGSMGPL LDLVKMFGDI CSGKYVARDE DKEKEYDRRR KDLFQLGTLL DGLILATRGS
TYSRVPTPVE GNQNTGTNLL GNFIAKCQEA KNIDQLVEDP FLKEECQSES ENIFTPFGGA
MSPDGRMLAD NVIIRVLGRG GFGDVVLVRN KMDSTDYAIK RIPLNAKSDK LNRKIAKEAK
FFAKLNHPNM VRYYYAWAED LIPIVEETSD DDSSLGAVPI PGKEKIGKKG KLKTGKSLED
KENKANLGGG DSLMPMNLRG LVKDHSIGVD AKEWSTPFGK PEGPKCASRM RQSKRSTPSG
GLKHLSECSS DDEDDDDSSE IDWDAESEEV EDEESDDSDE EDEDDGERLV QLNTETSTGA
DSVFERSTAD EDVVFTAESE DLNAKRRESI ELMEINTTTT SKSKLAIDVV PVRKPRILCI
QMEYCDRATL RQYIDENHCF NAPTEVWRIF SEVLCGLKYM HDMAMIHRDI KPLNIFLTSQ
NGVKIGDFGL ATLEAMSSKG KIVGGAAEKS TSIEAMLSPN GVKSKGSDVH QTRDIGTQLY
MAPELFVDEL VHKAPYTSKI DIYSAGVVLF EMFYRPLPPS MDRVSTLNNL RDDIKIPSDF
GAGLAAPMAG LARRTVEKML QRNPDERPTA DDLLNDEDLP MHTKEDATFR NLCEKVIKKR
DGRMNAWLLD KQFKEEVPTS LNYCYDVDIC LERAKYNNRE VLVETLRAEF CKILKIHSFE
KLHTHTLMPV STALAAASVR TKPVEVLDRS GVPVALPMDL RQNFVRFCVR NSVQRMKRFN
FGRVYSQTSA NGHPHERWEC CVDCIGPQCS SPSLEAELLL VACEMMIGSL PGMKFTLKIG
HAQLIEAQIR HLKLSDDVRA ELLDALHLIS VSDRPHSHKE KMDMLTPKIG AKAANIITKL
LIPVEDNFGA FKEKVACFRK KLKVDAARVL VDKAIRDLEE IVGTFKFCRT EAIEQISIVY
DSQTCYRPRT FGDGLLFQIQ VEKPSTIANN KRGRRQNVLA GGRYDSALLR ERHPRDFVYE
IPLCISGFGV AMDVVSQIRD SINKSANIPK TPQNHCKVLI CSMVQPDGSN LITQKFELAK
KLWSMGIEAD VFHIPVDDLE SLTEHRNRAS ITHILAVYNT LNEVICKTET SSETMDVDSA
ISSVWRGVQA LDGQSIHMTP CGGGPISSIS TPGEAHHHDD HHPGTPVIAS KCFRSSVSTT
VATTSIRPIS ATVANLNVIL VTSADRFHKV MKEKKRVESQ VRNHLTEFVA HFTSKTRIEV
LVCDIPADVI KKIVSELTKT SSEAEIDKLF DQLIQKHGKV DLSPLRRQFH ITLNGISTGS
AQVAILFYRQ SDNFYRYLV
