Protein: Eukaryotic translation initiation factor 2-alpha kinase 3 (EC 2.7.11.1) (PRKR-like endoplasmic reticulum kinase) (Pancreatic eIF2-alpha kinase) (Protein tyrosine kinase EIF2AK3) (EC 2.7.10.2) (Q9Z1Z1)
Organism: Rattus norvegicus (Rat)
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 conditions. Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as unfolded protein response (UPR) and low amino acid availability (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). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function (By similarity).
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}.
Interaction partners:
- Endoplasmic reticulum chaperone BiP
- Eukaryotic translation initiation factor 2 subunit 1
- Cyclic AMP-dependent transcription factor ATF-4
- Nuclear factor erythroid 2-related factor 2
- Cyclic AMP-dependent transcription factor ATF-6 alpha
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Presenilin-1
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
- Presenilin-2
- Interferon-induced protein with tetratricopeptide repeats 1
Sequence:
MERATQPRPRALLLLFLLLGCAAGISAVARARSLLAPTSDTAFGLGAAAAPTSAARVPAVATAEVTVEDAEALPAASGEQESRATESDDDVELRPRGRSLVIISTLDGRIAALDAENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGDLFQWDRDRESMEAVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKLRYICSALGCRRWDSDEMEEEEDILLLQRTQKTVRAVGPRSGSEKWNFSVGHFELRYIPDMETRAGFIESTFKLGGNKEDSKIISDVEEQDVDTVIKVSVADWKVMAFSKKGGRLEWEYQFCTPIASAWLVRDGKVIPISLFDDTSYTANEEVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRVSEKFPTRPKALESVNGESAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKYSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDSPHYSKNIRKKDPILLLHWWKEIFGTILLCIVATTFIVRRLFHPQPHRQRKESETQCQTESKYDSVSADNSDNSWNDIKHSGYVSRYLTDFEPIQCMGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLETPPEKWQEEMDEIWLKDESTDWPLSSPSPMDAPSVKIRQMDPFSTKEQIEVIAPSPERSRSFSVGISCGRTSSSESQFSPLEFSGTDCGDNSDSEDAAHNLQDSCLTDCDMEDGTVDGDDEGHSFELCPSEASPYTRSREGTSSSIVFEDSGCDNASSKEDPRMNRLHNGHHYVNKLTEFKHSSSRSSSEATLSTSPTRPTTLSLDFTRNTVDRLQPSSPKVYLYIQMQLCRKENLKDWMNRRCSMEDREHRVCLHIFLQIAEAVQFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYATHTGQVGTKLYMSPEQIHGNNYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPQEHMMVQDMLSPSPMERPEATDIIENAVFENLEFPGKTVLRQRSRSLSSSGTKHSRQPSSTFSPLPGN