Eif2ak3
entrez
29702
canonical
uniprot
Q9Z1Z1
canonical
ensembl
ENSRNOG00000006069
resolver
ensembl
ENSRNOG00055019871
resolver
ensembl
ENSRNOG00060016036
resolver
ensembl
ENSRNOG00065005152
resolver
ensp
ENSRNOP00000008451
resolver
ensp
ENSRNOP00055027608
resolver
ensp
ENSRNOP00060022076
resolver
ensp
ENSRNOP00065005229
resolver
enst
ENSRNOT00000008451
resolver
enst
ENSRNOT00055033992
resolver
enst
ENSRNOT00060027487
resolver
enst
ENSRNOT00065007558
resolver
genesymbol
Eif2ak3
resolver
genesymbol_syn
Pek
resolver
genesymbol_syn
Perk
resolver
uniprot_entry
E2AK3_RAT
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by HSPA5/BIP in absence of stress (By similarity). Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in trans-autophosphorylation and kinase activity induction (By similarity). Inactivated following phosphorylation at Thr-794 by AKT (AKT1, AKT2 and/or AKT3) (By similarity). Inhibited by ATAD3A at mitochondria-endoplasmic reticulum contact sites, providing a safe haven for mitochondrial protein translation during ER stress (By similarity). {ECO:0000250|UniProtKB:Q9NZJ5, ECO:0000250|UniProtKB:Q9Z2B5}.
uniprot
proteins
amino_acid_sequence
MERATQPRPRALLLLFLLLGCAAGISAVARARSLLAPTSDTAFGLGAAAAPTSAARVPAVATAEVTVEDAEALPAASGEQESRATESDDDVELRPRGRSLVIISTLDGRIAALDAENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGDLFQWDRDRESMEAVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKLRYICSALGCRRWDSDEMEEEEDILLLQRTQKTVRAVGPRSGSEKWNFSVGHFELRYIPDMETRAGFIESTFKLGGNKEDSKIISDVEEQDVDTVIKVSVADWKVMAFSKKGGRLEWEYQFCTPIASAWLVRDGKVIPISLFDDTSYTANEEVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRVSEKFPTRPKALESVNGESAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKYSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDSPHYSKNIRKKDPILLLHWWKEIFGTILLCIVATTFIVRRLFHPQPHRQRKESETQCQTESKYDSVSADNSDNSWNDIKHSGYVSRYLTDFEPIQCMGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLETPPEKWQEEMDEIWLKDESTDWPLSSPSPMDAPSVKIRQMDPFSTKEQIEVIAPSPERSRSFSVGISCGRTSSSESQFSPLEFSGTDCGDNSDSEDAAHNLQDSCLTDCDMEDGTVDGDDEGHSFELCPSEASPYTRSREGTSSSIVFEDSGCDNASSKEDPRMNRLHNGHHYVNKLTEFKHSSSRSSSEATLSTSPTRPTTLSLDFTRNTVDRLQPSSPKVYLYIQMQLCRKENLKDWMNRRCSMEDREHRVCLHIFLQIAEAVQFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYATHTGQVGTKLYMSPEQIHGNNYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPQEHMMVQDMLSPSPMERPEATDIIENAVFENLEFPGKTVLRQRSRSLSSSGTKHSRQPSSTFSPLPGN
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR) (PubMed:9819435). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (By similarity). The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes (By similarity). In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites (By similarity). In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity). {ECO:0000250|UniProtKB:Q9NZJ5, ECO:0000250|UniProtKB:Q9Z2B5, ECO:0000269|PubMed:9819435}.
uniprot
proteins
mass_dalton
124770
uniprot
proteins
mutagenesis
MUTAGEN 614; /note="K->A: Loss of activity."; /evidence="ECO:0000269|PubMed:10026192
uniprot
proteins
post_translational_modification
PTM: Oligomerization of the N-terminal ER luminal domain by ER stress promotes EIF2AK3/PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-974 on the kinase activation loop (By similarity). Autophosphorylated at Tyr-611 following endoplasmic reticulum stress, leading to activate its activity (By similarity). Dephosphorylated at Tyr-611 by PTPN1/PTP1B, leading to inactivate its enzyme activity (By similarity). Phosphorylation at Thr-794 by AKT (AKT1, AKT2 and/or AKT3) inactivates EIF2AK3/PERK (By similarity). {ECO:0000250|UniProtKB:Q9NZJ5, ECO:0000250|UniProtKB:Q9Z2B5}.; PTM: ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity. {ECO:0000250|UniProtKB:Q9NZJ5}.
uniprot
proteins
protein_family
GCN2 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10026192
uniprot
proteins
pubmed
10854322
uniprot
proteins
pubmed
9819435
uniprot
proteins
sequence_length
1108
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9Z2B5}; Single-pass type I membrane protein {ECO:0000255}. Note=Localizes to the Localizes to endoplasmic reticulum membrane (By similarity). Also present at mitochondria-endoplasmic reticulum contact sites; where it interacts with ATAD3A (By similarity). {ECO:0000250|UniProtKB:Q9NZJ5, ECO:0000250|UniProtKB:Q9Z2B5}.
uniprot
proteins
transmembrane_region
TRANSMEM 507..527; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins