4X7O

Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4x7oa_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ], Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Pkinase_Tyr	e4x7oA1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (utative)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (utative)

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Eukaryotic translation initiation factor 2-alpha kinase 3,Eukaryotic translation initiation factor 2-alpha kinase 3	protein serine/threonine kinase activity eukaryotic translation initiation factor 2alpha kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein phosphatase binding phosphatase binding protein binding binding enzyme binding protein serine/threonine kinase activity eukaryotic translation initiation factor 2alpha kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein phosphatase binding phosphatase binding protein binding binding enzyme binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding identical protein binding Hsp90 protein binding heat shock protein binding protein serine kinase activity	cellular response to stimulus cellular response to inorganic substance cellular response to metal ion response to manganese-induced endoplasmic reticulum stress response to stimulus cellular response to manganese ion cellular response to chemical stress response to inorganic substance cellular response to chemical stimulus cellular response to stress response to metal ion response to stress response to chemical cellular process cellular response to stimulus cellular response to inorganic substance cellular response to metal ion response to manganese-induced endoplasmic reticulum stress response to stimulus cellular response to manganese ion cellular response to chemical stress response to inorganic substance cellular response to chemical stimulus cellular response to stress response to metal ion response to stress response to chemical cellular process response to manganese ion response to endoplasmic reticulum stress developmental process multicellular organismal process ossification bone mineralization animal organ development anatomical structure development biomineral tissue development tissue development cellular developmental process connective tissue development cell development multicellular organism development skeletal system development cell differentiation chondrocyte differentiation chondrocyte development cartilage development system development regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process organic substance metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process cellular response to nutrient levels response to nutrient levels response to starvation cellular response to glucose starvation cellular response to starvation organonitrogen compound biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation negative regulation of cellular process translational initiation protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of translational initiation in response to stress organonitrogen compound metabolic process regulation of translational initiation regulation of protein metabolic process negative regulation of metabolic process negative regulation of translational initiation primary metabolic process translation negative regulation of cellular biosynthetic process negative regulation of gene expression negative regulation of biosynthetic process regulation of translation negative regulation of macromolecule biosynthetic process negative regulation of nervous system process system process regulation of developmental process regulation of myelination regulation of system process regulation of nervous system development axon ensheathment ensheathment of neurons regulation of multicellular organismal process regulation of multicellular organismal development nervous system process nervous system development regulation of nervous system process myelination negative regulation of myelination negative regulation of multicellular organismal process cell surface receptor signaling pathway signaling insulin-like growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication signal transduction enzyme-linked receptor protein signaling pathway protein phosphorylation protein autophosphorylation phosphorylation macromolecule modification phosphate-containing compound metabolic process protein modification process phosphorus metabolic process regulation of translational initiation by eIF2 alpha phosphorylation regulation of translation in response to stress regulation of translational initiation in response to stress peptidyl-serine modification peptidyl-serine phosphorylation peptidyl-amino acid modification response to biotic stimulus cellular response to biotic stimulus ER overload response ER-nucleus signaling pathway cellular response to amino acid starvation response to amino acid starvation response to organic substance cellular response to topologically incorrect protein endoplasmic reticulum unfolded protein response cellular response to unfolded protein response to unfolded protein response to topologically incorrect protein cellular response to organic substance regulation of cellular response to stress regulation of phosphate metabolic process regulation of translation initiation in response to endoplasmic reticulum stress eiF2alpha phosphorylation in response to endoplasmic reticulum stress regulation of response to stimulus regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation regulation of response to endoplasmic reticulum stress regulation of response to stress regulation of translation in response to endoplasmic reticulum stress regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation regulation of phosphorylation protein localization regulation of localization cellular localization regulation of protein localization positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization to organelle positive regulation of protein localization regulation of catalytic activity positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of molecular function regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of proteolysis proteolysis regulation of endopeptidase activity activation of cysteine-type endopeptidase activity involved in apoptotic process regulation of cysteine-type endopeptidase activity regulation of peptidase activity positive regulation of catalytic activity regulation of molecular function positive regulation of hydrolase activity positive regulation of cysteine-type endopeptidase activity regulation of hydrolase activity positive regulation of endopeptidase activity positive regulation of proteolysis regulation of cytokine production cytokine production regulation of vascular endothelial growth factor production vascular endothelial growth factor production positive regulation of multicellular organismal process positive regulation of vascular endothelial growth factor production positive regulation of cytokine production blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development negative regulation of translation in response to stress intracellular signal transduction calcium-mediated signaling intracellular signaling cassette PERK-mediated unfolded protein response integrated stress response signaling pancreas development endocrine system development endocrine pancreas development cellular component organization organelle organization cellular component organization or biogenesis endoplasmic reticulum organization endomembrane system organization regulation of signal transduction regulation of programmed cell death intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress regulation of intrinsic apoptotic signaling pathway regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway regulation of intracellular signal transduction intrinsic apoptotic signaling pathway regulation of signaling regulation of apoptotic process cell death apoptotic signaling pathway regulation of cell communication apoptotic process programmed cell death regulation of apoptotic signaling pathway nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase I regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase I positive regulation of RNA metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of transcription by RNA polymerase I regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process cellular response to cold response to abiotic stimulus response to cold response to temperature stimulus	membrane cellular anatomical entity intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm membrane-bounded organelle organelle subcompartment intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle organelle nuclear outer membrane-endoplasmic reticulum membrane network membrane cellular anatomical entity intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm membrane-bounded organelle organelle subcompartment intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR000719	Protein kinase domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR011047	Quinoprotein alcohol dehydrogenase-like superfamily	Homologous Superfamily
A	IPR015943	WD40/YVTN repeat-like-containing domain superfamily	Homologous Superfamily
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q9NZJ5	Wolcott-Rallison syndrome progressive supranuclear palsy status epilepticus acquired metabolic disease Complex Partial Status Epilepticus myocardial ischemia osteogenesis imperfecta pancreatic intraductal papillary-mucinous neoplasm psoriasis B-cell chronic lymphocytic leukemia coronary artery disease intellectual disability myopathy osteosarcoma cancer Wolcott-Rallison syndrome progressive supranuclear palsy status epilepticus acquired metabolic disease Complex Partial Status Epilepticus myocardial ischemia osteogenesis imperfecta pancreatic intraductal papillary-mucinous neoplasm psoriasis B-cell chronic lymphocytic leukemia coronary artery disease intellectual disability myopathy osteosarcoma cancer diabetes mellitus multiple epiphyseal dysplasia ovarian cancer

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.