E2AKA_CAEEL
ID E2AKA_CAEEL Reviewed; 1077 AA.
AC Q19192; Q20458;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase pek-1 {ECO:0000305|PubMed:10677345};
DE EC=2.7.11.1 {ECO:0000269|PubMed:10677345};
DE AltName: Full=CePEK;
DE Short=PEK;
DE AltName: Full=PRKR-like endoplasmic reticulum kinase;
DE Short=PERK;
DE Flags: Precursor;
GN Name=pek-1; ORFNames=F46C3.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
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 [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=11779465; DOI=10.1016/s0092-8674(01)00612-2;
RA Shen X., Ellis R.E., Lee K., Liu C.-Y., Yang K., Solomon A., Yoshida H.,
RA Morimoto R., Kurnit D.M., Mori K., Kaufman R.J.;
RT "Complementary signaling pathways regulate the unfolded protein response
RT and are required for C. elegans development.";
RL Cell 107:893-903(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 [4]
RP FUNCTION.
RX PubMed=16184190; DOI=10.1371/journal.pgen.0010037;
RA Shen X., Ellis R.E., Sakaki K., Kaufman R.J.;
RT "Genetic interactions due to constitutive and inducible gene regulation
RT mediated by the unfolded protein response in C. elegans.";
RL PLoS Genet. 1:e37-e37(2005).
RN [5]
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).
CC -!- FUNCTION: Phosphorylates the alpha subunit of eukaryotic translation-
CC initiation factor 2 (eIF2alpha), leading to its inactivation and thus
CC to a rapid reduction of translational initiation and repression of
CC global protein synthesis (PubMed:10677345). May phosphorylate eIF2alpha
CC during hypoxia (PubMed:20733002). Proposed to have a role in
CC alleviating endoplasmic reticulum stress (PubMed:10677345,
CC PubMed:11779465, PubMed:16184190). {ECO:0000269|PubMed:10677345,
CC ECO:0000269|PubMed:11779465, ECO:0000303|PubMed:20733002}.
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:0000269|PubMed:10677345};
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:0000269|PubMed:10677345};
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 (By similarity). {ECO:0000250|UniProtKB:Q9Z2B5}.
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 -!- TISSUE SPECIFICITY: Expressed in intestinal cells.
CC {ECO:0000269|PubMed:11779465}.
CC -!- INDUCTION: By ER stress. {ECO:0000269|PubMed:10677345}.
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 -!- DISRUPTION PHENOTYPE: After L2 growth stage movement is subdued and
CC development is stunted. Increased sensitivity to tunicamycin which
CC induces an unfolded protein response symptomatic of endoplasmic
CC reticulum stress. {ECO:0000269|PubMed:11779465}.
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; AF193341; AAF61201.1; -; mRNA.
DR EMBL; AF435953; AAL30829.1; -; mRNA.
DR EMBL; Z66563; CAA91470.1; -; Genomic_DNA.
DR EMBL; Z68104; CAA91470.1; JOINED; Genomic_DNA.
DR PIR; T20579; T20579.
DR RefSeq; NP_509912.1; NM_077511.6.
DR AlphaFoldDB; Q19192; -.
DR SMR; Q19192; -.
DR STRING; 6239.F46C3.1; -.
DR EPD; Q19192; -.
DR PaxDb; Q19192; -.
DR PeptideAtlas; Q19192; -.
DR EnsemblMetazoa; F46C3.1.1; F46C3.1.1; WBGene00003970.
DR GeneID; 181334; -.
DR KEGG; cel:CELE_F46C3.1; -.
DR UCSC; F46C3.1; c. elegans.
DR CTD; 181334; -.
DR WormBase; F46C3.1; CE18695; WBGene00003970; pek-1.
DR eggNOG; KOG1033; Eukaryota.
DR GeneTree; ENSGT00940000163863; -.
DR HOGENOM; CLU_009091_0_0_1; -.
DR InParanoid; Q19192; -.
DR OMA; GHIVSVW; -.
DR OrthoDB; 64059at2759; -.
DR PhylomeDB; Q19192; -.
DR Reactome; R-CEL-1169408; ISG15 antiviral mechanism.
DR Reactome; R-CEL-381042; PERK regulates gene expression.
DR PRO; PR:Q19192; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003970; Expressed in embryo and 4 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:WormBase.
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:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IDA:WormBase.
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:0030968; P:endoplasmic reticulum unfolded protein response; IMP:WormBase.
DR GO; GO:0030308; P:negative regulation of cell growth; IGI:WormBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; IC:WormBase.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0010939; P:regulation of necrotic cell death; IGI:WormBase.
DR GO; GO:0035966; P:response to topologically incorrect protein; IMP:WormBase.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR InterPro; IPR002372; PQQ_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 Pfam; PF01011; PQQ; 1.
DR SMART; SM00564; PQQ; 1.
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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1077
FT /note="Eukaryotic translation initiation factor 2-alpha
FT kinase pek-1"
FT /id="PRO_0000024325"
FT TOPO_DOM 24..453
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..1077
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 604..1076
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 727..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 795..815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 933
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 610..618
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 633
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1077 AA; 119639 MW; DA15615994FC36EC CRC64;
MSVYYIVLAG FLLFMALVPF NAGQQYIDDD IEVVSSCQNG YVQNAGCDQN SQVNIIITAT
LDGVVTALDG ETGEMIWRYE DAPLLRGTLS TSDPIDIGGT SLQLMPTLDG RLFSYTHNTN
LIEPLPITTD SLLESTIRLG QDAVAGGKSV TTKGFDLFTG EQKYECSMES CGPGDTETPK
NPIILIRRTT NSIRAMDTLR GIERWNLSTA EIGVTLAGGI TSPTLVSDVK ILLQPPDGVI
VAVDKYNREE WKTNVDGHIV SVWQVYGNQI GEISIFDPSN IFTTQYEVMQ REQHNLQTQS
SLLYMGTSNG FPFIIQSPKA KNNLKQRMNA LPELSTMTEL TNPRFCTANE ETRSLAYNVK
DETLRLVLHN AFRHSQSKAI EDKSLSGSSA RRKLQIIASD TEVSAQRIGT ENLRSTSVSK
SGDYGYLVLE SEPQRVKFKV NSPITLMQTI FSYIFNPTAV VSFLAGLIGV TVAVVYNKIA
KSSPRMIEHL SSTESAETES ASHRTRTTSF APTDDEIERF VEEGSDLSTT PIGAIHRKPL
MPIEKSNIET HTQPQIKPVQ RLVKTDIDTD EDSFSNDEKK RLLRNRTISR SSLEGFTSRF
ANEFEVKKVI GHGGFGVVFR AQSITDMNEY AVKRIAVADN DKARNRVLRE ARALAMFDHP
GIIRYFYAWE ERPPKGFQEK EDENLLGKIK AEKLAKLHEI KKAKKHTSEG KRVRSADTAS
FAESFAMPPV VGNTTDAENS WSTSAKPQEV GAKRTTSESK LGLHGGSDRT TAELKEESVA
FSESDEESDT TEDSSSSDES PSSSSGSSID DEPKKYNSSS GGIEFVDGSD DVDNEAVKET
KKEIAVIEEL SIHNRAMIVE TENQELEVRE RNDTGDCAYL YIVMQLCAEK TLEDWIRRSK
TMESRPLFTM KNWIKQLASG LEYLHNKGFI HRDLKPGNVF FSLDSTHGHQ ILKIGDLGLA
TKTDGAPKIT VRQDSDSSAK HTKNVGTRSY MSPEQLKHQQ YTEKVDIFAL GLVATELIIS
FSTASERIHT FADFQKGDIP AILDNVPESR DFLLQLTSLE PSERPTAHEV ATHKFLQ
