E2AK3_DROME
ID E2AK3_DROME Reviewed; 1162 AA.
AC Q9NIV1; Q8SX61; Q9VNB8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase;
DE EC=2.7.11.1;
DE AltName: Full=PRKR-like endoplasmic reticulum kinase;
DE Short=DmPEK;
DE Short=PEK;
DE Short=PERK;
DE Flags: Precursor;
GN Name=PEK; Synonyms=EIF2AK3; ORFNames=CG2087;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=10677345; DOI=10.1042/bj3460281;
RA Sood R., Porter A.C., Ma K., Quilliam L.A., Wek R.C.;
RT "Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in
RT humans, Drosophila melanogaster and Caenorhabditis elegans that mediate
RT translational control in response to endoplasmic reticulum stress.";
RL Biochem. J. 346:281-293(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RA Pomar-Ballestero N.;
RL Thesis (2001), Universidad Autonoma de Madrid, Spain.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-624; SER-797; THR-818 AND
RP THR-1028, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Phosphorylates the alpha subunit of eukaryotic translation-
CC initiation factor 2 (EIF2), leading to its inactivation and thus to a
CC rapid reduction of translational initiation and repression of global
CC protein synthesis. {ECO:0000250}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Perturbation in protein folding in the endoplasmic
CC reticulum (ER) promotes reversible dissociation from HSPA5/BIP and
CC oligomerization, resulting in transautophosphorylation and kinase
CC activity induction. {ECO:0000250}.
CC -!- SUBUNIT: Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in
CC ER-stressed cells (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}.
CC -!- INDUCTION: By ER stress.
CC -!- DOMAIN: The lumenal domain senses perturbations in protein folding in
CC the ER, probably through reversible interaction with HSPA5/BIP.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. GCN2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF193340; AAF61200.1; -; mRNA.
DR EMBL; AJ313085; CAC85207.1; -; mRNA.
DR EMBL; AE014297; AAF52028.2; -; Genomic_DNA.
DR EMBL; AY094831; AAM11184.1; -; mRNA.
DR RefSeq; NP_649538.1; NM_141281.3.
DR AlphaFoldDB; Q9NIV1; -.
DR SMR; Q9NIV1; -.
DR BioGRID; 65862; 16.
DR DIP; DIP-22099N; -.
DR IntAct; Q9NIV1; 1.
DR STRING; 7227.FBpp0078417; -.
DR GlyGen; Q9NIV1; 6 sites.
DR iPTMnet; Q9NIV1; -.
DR PaxDb; Q9NIV1; -.
DR PRIDE; Q9NIV1; -.
DR DNASU; 40653; -.
DR EnsemblMetazoa; FBtr0078770; FBpp0078417; FBgn0037327.
DR GeneID; 40653; -.
DR KEGG; dme:Dmel_CG2087; -.
DR CTD; 40653; -.
DR FlyBase; FBgn0037327; PEK.
DR VEuPathDB; VectorBase:FBgn0037327; -.
DR eggNOG; KOG1033; Eukaryota.
DR GeneTree; ENSGT00940000163863; -.
DR InParanoid; Q9NIV1; -.
DR OrthoDB; 64059at2759; -.
DR PhylomeDB; Q9NIV1; -.
DR Reactome; R-DME-381042; PERK regulates gene expression.
DR SignaLink; Q9NIV1; -.
DR BioGRID-ORCS; 40653; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40653; -.
DR PRO; PR:Q9NIV1; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037327; Expressed in wing disc and 28 other tissues.
DR ExpressionAtlas; Q9NIV1; baseline and differential.
DR Genevisible; Q9NIV1; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004686; F:elongation factor-2 kinase activity; IDA:FlyBase.
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:0036499; P:PERK-mediated unfolded protein response; IGI:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:FlyBase.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:FlyBase.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IMP:FlyBase.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00564; PQQ; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Endoplasmic reticulum; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Stress response; Transferase;
KW Translation regulation; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..1162
FT /note="Eukaryotic translation initiation factor 2-alpha
FT kinase"
FT /id="PRO_0000024326"
FT TOPO_DOM 40..537
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..558
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 559..1162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 642..1130
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 498..517
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1135..1162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 813..827
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 980
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 648..656
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 671
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 797
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 818
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1028
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 629
FT /note="H -> D (in Ref. 1; AAF61200)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1162 AA; 131039 MW; F3D6B4C87159D95B CRC64;
MQDDLDGIVR HRRRSLSFLQ IVTLTMAGLV AFDPAQVLAG HPTTDSELQT AGSPRPPGLE
HCVDQEERRV ARRLLYISTL DGRLSALDIA KSGKLRWSVP TGPGPLISSS IHRLELTNNG
QFVRMIPSLS GGIYKFDGDS IDPIPITAEH LLSSSAKFSD DLVISGGKET RSYGVSVRTG
QLLYECSLNG CVNSTEEGLA IDDTIREPDE EDQLEDGEQL RDEAGYIVRH DPLLDDVIIV
RRQTQTVRAV ESRTGVERWN FSVGQHELDL VRPSECQLQP RDELELAVLD VDIKVVVPEG
IICAFSKSEP QTMLWKYKFD HPIVSAWNTN ADDELQPIDL FSSAQWLWDQ DENDTELPNA
PQSPPSIYLG MYDKQLYIQE SIRLRQEIMD QTKVYQQLTG DTSLMPRIPW KPISASSKSL
VIFRKDQEDP EMIAEGAVAQ GGELVPYDDE NFAVAAQSVL NASEFVNGNG FYFYTTGDLN
GPQECSTQNN PTDLPAITAP TSPTNATSEG TEATGNHSVN DDLGFSLDDI DAPVKVVILS
LWFWWKEIVV IAFTSAVILN IFMGQRNQRV EREYLVIERH VPVQTAIEAT EASTQALLGP
VVPMQRPGNR FSFPPGQANQ RTISESTTHS GEHYTSRFQS DFELMQCLGR GGFGVVFEAK
NKLDENRYAI KRITLPNKES SRQRVLREAR TLASCEHHNI VRYFHSWTET PPTGWQEEED
RKLLAHELST SIQIETPDDS TMPSLTEQLK EKRQQQLLSW VSDAANSTAC SHDFHLPGES
SLKNIREEYD YDEEEDSLIE FRSESQSAAL RAEEEDDTDD DYEEDEEQQG DHEKRHRSSV
SIDIHSASFD LKNINYSQHQ LVSNSFQIES VRPKSSGSDD ANDDNKARRK PLTLALAQNH
NNNQNGSQPT PSSATILNGT VAKPSKVYLY IQMQLCRKES LRDWLRDNRS ETRAAHIGDI
FHQIVDAVDY VHLKGLIHRD LKPSNIFFSQ DGQIKIGDFG LVTDMADIPN LVAKCGDQSG
LPSCARHTQQ VGTHLYMSPE QLLGQHYDYK VDIYSLGLIF FELHVYFSTE MERIKTLRSL
RDGQYPKDFA VNYPQQYDLL QQMLSAQPEQ RPQTKQLKSQ LRNILQLPHL LSEGQSEQAE
LAERARRLSR SRTFSSSSEP HQ
