Phospho-PERK (Ser715) Antibody - #AF3523

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. 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.

Oligomerization of the N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-982 on the kinase activation loop (By similarity). Autophosphorylated. Phosphorylated at Tyr-619 following endoplasmic reticulum stress, leading to activate its tyrosine-protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity.

N-glycosylated.

ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity.

Endoplasmic reticulum membrane>Single-pass type I membrane protein.

Ubiquitous. A high level expression is seen in secretory tissues.

Forms dimers with HSPA5/BIP in resting cells (By similarity). Oligomerizes in ER-stressed cells (By similarity). Interacts with DNAJC3 and MFN2 (By similarity). Interacts with TMEM33. Interacts with PDIA6.

The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.