Annotations: 2KR6

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF01080	e2kr6A1	A: alpha arrays	X: Presenilin family intramembrane aspartate proteases (From Topology)	H: Presenilin family intramembrane aspartate proteases (From Topology)	T: Presenilin family intramembrane aspartate proteases	F: PF01080	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.472.100	Mainly Alpha	Orthogonal Bundle	Cyclin A	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01080	Presenilin (Presenilin)	Presenilin	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Presenilin-1	aspartic-type peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity aspartic endopeptidase activity, intramembrane cleaving aspartic-type endopeptidase activity catalytic activity endopeptidase activity cell adhesion molecule binding cadherin binding protein binding binding PDZ domain binding protein domain specific binding aspartic-type peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity aspartic endopeptidase activity, intramembrane cleaving aspartic-type endopeptidase activity catalytic activity endopeptidase activity cell adhesion molecule binding cadherin binding protein binding binding PDZ domain binding protein domain specific binding signaling receptor binding growth factor receptor binding beta-catenin binding calcium channel activity monoatomic cation transmembrane transporter activity monoatomic ion channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity ATPase binding enzyme binding	cellular response to stimulus regulation of biological process regulation of signaling regulation of cellular process cell surface receptor signaling pathway response to stimulus regulation of Wnt signaling pathway signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway biological regulation regulation of signal transduction cell communication regulation of response to stimulus cellular response to stimulus regulation of biological process regulation of signaling regulation of cellular process cell surface receptor signaling pathway response to stimulus regulation of Wnt signaling pathway signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway biological regulation regulation of signal transduction cell communication regulation of response to stimulus regulation of cell communication cellular process signal transduction Wnt signaling pathway inorganic ion homeostasis intracellular calcium ion homeostasis homeostatic process calcium ion homeostasis endoplasmic reticulum calcium ion homeostasis cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis cellular localization sequestering of calcium ion maintenance of location in cell maintenance of location localization regulation of protein modification process regulation of protein phosphorylation negative regulation of biological process negative regulation of phosphate metabolic process negative regulation of cellular metabolic process regulation of primary metabolic process organic substance metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process negative regulation of cellular process protein metabolic process protein modification process phosphorus metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process organonitrogen compound metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process metabolic process regulation of phosphorylation regulation of phosphorus metabolic process macromolecule metabolic process negative regulation of phosphorylation regulation of metabolic process cerebral cortex cell migration developmental process multicellular organismal process head development forebrain development animal organ development brain development nervous system development pallium development cerebral cortex development multicellular organism development telencephalon cell migration central nervous system development forebrain cell migration anatomical structure development cell migration telencephalon development cell motility system development behavior system process learning or memory nervous system process cognition memory positive regulation of proteasomal protein catabolic process catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process organonitrogen compound catabolic process proteasomal protein catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process organic substance catabolic process regulation of protein catabolic process cerebellum development metencephalon development hindbrain development import into cell nitrogen compound transport carboxylic acid transmembrane transport transport amino acid transmembrane transport L-amino acid transport L-glutamate import L-glutamate import across plasma membrane organic acid transmembrane transport organic anion transport carboxylic acid transport organic substance transport import across plasma membrane establishment of localization organic acid transport transmembrane transport amino acid transport acidic amino acid transport dicarboxylic acid transport L-alpha-amino acid transmembrane transport amino acid import across plasma membrane L-glutamate transmembrane transport cellular developmental process astrocyte differentiation cell development astrocyte activation glial cell development neurogenesis astrocyte development gliogenesis cell differentiation response to stress defense response cell activation glial cell differentiation glial cell activation inflammatory response neuroinflammatory response amyloid precursor protein catabolic process amyloid precursor protein metabolic process anatomical structure morphogenesis skeletal system development skeletal system morphogenesis animal organ morphogenesis axonogenesis cell projection organization regulation of cell differentiation regulation of neurogenesis neuron projection development regulation of cell development cell projection morphogenesis neuron differentiation neuron projection morphogenesis negative regulation of cellular component organization regulation of cell projection organization generation of neurons negative regulation of axonogenesis negative regulation of multicellular organismal process regulation of neuron projection development regulation of cellular component organization regulation of developmental process plasma membrane bounded cell projection morphogenesis cell morphogenesis cellular component organization regulation of nervous system development negative regulation of neurogenesis regulation of axonogenesis negative regulation of nervous system development regulation of multicellular organismal process negative regulation of cell differentiation cellular component organization or biogenesis negative regulation of cell projection organization regulation of anatomical structure morphogenesis regulation of multicellular organismal development plasma membrane bounded cell projection organization negative regulation of developmental process axon development negative regulation of neuron projection development cell morphogenesis involved in neuron differentiation negative regulation of cell development neuron development regulation of plasma membrane bounded cell projection organization vasculature development blood vessel development circulatory system development negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process Notch signaling pathway postsynapse organization regulation of postsynapse organization regulation of synapse organization cell junction organization regulation of synapse structure or activity synapse organization regulation of biological quality regulation of protein binding positive regulation of molecular function regulation of molecular function positive regulation of protein binding regulation of binding positive regulation of binding neuron cellular homeostasis amyloid-beta metabolic process amide metabolic process pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process carbohydrate derivative metabolic process organophosphate catabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process regulation of ATP metabolic process cellular catabolic process regulation of purine nucleotide catabolic process regulation of small molecule metabolic process regulation of nucleotide metabolic process small molecule metabolic process purine ribonucleotide catabolic process nucleoside phosphate metabolic process pyruvate metabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process positive regulation of ATP metabolic process nucleoside diphosphate metabolic process positive regulation of carbohydrate metabolic process monocarboxylic acid metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process positive regulation of purine nucleotide catabolic process positive regulation of cellular metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process positive regulation of cellular process purine nucleotide catabolic process carbohydrate derivative catabolic process positive regulation of glycolytic process organic cyclic compound catabolic process purine-containing compound metabolic process ADP metabolic process purine ribonucleoside diphosphate metabolic process purine ribonucleoside diphosphate catabolic process ribonucleotide catabolic process positive regulation of phosphate metabolic process positive regulation of nucleotide catabolic process glycolytic process pyridine-containing compound metabolic process pyridine nucleotide metabolic process nicotinamide nucleotide metabolic process regulation of carbohydrate catabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of phosphorus metabolic process nucleotide metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process positive regulation of nucleotide metabolic process purine nucleotide metabolic process ribonucleotide metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process regulation of carbohydrate metabolic process ribonucleoside triphosphate metabolic process nucleotide catabolic process purine nucleoside triphosphate metabolic process carbohydrate metabolic process ADP catabolic process carboxylic acid metabolic process generation of precursor metabolites and energy regulation of glycolytic process positive regulation of purine nucleotide metabolic process organophosphate metabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process positive regulation of small molecule metabolic process positive regulation of cellular component organization positive regulation of amyloid fibril formation regulation of amyloid fibril formation amyloid fibril formation positive regulation of supramolecular fiber organization regulation of supramolecular fiber organization supramolecular fiber organization somitogenesis epithelium development chordate embryonic development segmentation anterior/posterior pattern specification pattern specification process embryo development tissue development regionalization embryo development ending in birth or egg hatching somite development anatomical structure formation involved in morphogenesis autophagosome assembly organelle assembly vacuole organization macroautophagy autophagy autophagosome organization cellular component biogenesis organelle organization cellular component assembly process utilizing autophagic mechanism negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death brain morphogenesis negative regulation of signaling negative regulation of cell communication negative regulation of apoptotic signaling pathway negative regulation of response to stimulus negative regulation of signal transduction apoptotic signaling pathway regulation of apoptotic signaling pathway cell population proliferation epithelial cell proliferation neuron apoptotic process regulation of core promoter binding regulation of DNA binding negative regulation of binding regulation of transcription regulatory region DNA binding negative regulation of molecular function negative regulation of core promoter binding negative regulation of DNA binding negative regulation of transcription regulatory region DNA binding cell activation involved in immune response astrocyte activation involved in immune response immune response immune effector process immune system process monoatomic ion transport monoatomic cation transport calcium ion transport metal ion transport intracellular signal transduction mitochondrial transport negative regulation of gene expression regulation of tumor necrosis factor production positive regulation of macromolecule biosynthetic process positive regulation of tumor necrosis factor superfamily cytokine production positive regulation of biosynthetic process cytokine production regulation of cytokine production tumor necrosis factor superfamily cytokine production positive regulation of tumor necrosis factor production tumor necrosis factor production regulation of tumor necrosis factor superfamily cytokine production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of cytokine production positive regulation of cellular biosynthetic process response to oxidative stress neuron projection maintenance neuron projection organization cellular response to nitrogen compound response to organic substance response to organonitrogen compound response to endogenous stimulus response to oxygen-containing compound response to nitrogen compound cellular response to amyloid-beta cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to chemical stimulus cellular response to organonitrogen compound response to chemical cellular response to organic substance response to amyloid-beta membrane protein proteolysis membrane protein ectodomain proteolysis cellular response to stress DNA damage response cell fate specification cell fate commitment positive regulation of coagulation coagulation regulation of coagulation regulation of localization positive regulation of L-glutamate import across plasma membrane positive regulation of amine transport regulation of L-glutamate import across plasma membrane positive regulation of transmembrane transport regulation of amino acid transport regulation of amino acid transmembrane transport regulation of transport positive regulation of organic acid transport amine transport regulation of amino acid import across plasma membrane regulation of transmembrane transport positive regulation of transport positive regulation of amino acid transport regulation of organic acid transport regulation of amine transport regulation of resting membrane potential regulation of membrane potential choline transport organic cation transport negative regulation of proteolysis negative regulation of proteolysis involved in protein catabolic process negative regulation of ubiquitin-dependent protein catabolic process negative regulation of catabolic process positive regulation of programmed cell death positive regulation of apoptotic process positive regulation of dendritic spine development regulation of dendritic spine development positive regulation of developmental process dendrite development dendritic spine development protein localization establishment of protein localization nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization import into nucleus cellular macromolecule localization establishment of localization in cell regulation of intracellular transport positive regulation of protein localization to nucleus positive regulation of protein import into nucleus intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus establishment of protein localization to organelle positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport regulation of protein localization positive regulation of nucleocytoplasmic transport regulation of protein localization to nucleus positive regulation of protein transport regulation of protein import into nucleus protein import into nucleus positive regulation of intracellular transport regulation of establishment of protein localization regulation of protein transport regulation of cellular localization protein transport macromolecule localization protein localization to organelle Cajal-Retzius cell differentiation central nervous system neuron differentiation cerebral cortex neuron differentiation neural tube development tube development dorsal/ventral pattern formation dorsal/ventral neural tube patterning neural tube patterning skin development skin morphogenesis lymphocyte activation leukocyte activation T cell activation involved in immune response T cell activation leukocyte activation involved in immune response lymphocyte activation involved in immune response protein catabolic process at postsynapse protein catabolic process at synapse sensory organ development eye development retina development in camera-type eye visual system development neural retina development camera-type eye development sensory system development regulation of synaptic vesicle cycle synaptic vesicle cycle regulation of vesicle-mediated transport vesicle-mediated transport vesicle-mediated transport in synapse heart morphogenesis embryonic heart tube development tube morphogenesis embryonic heart tube morphogenesis heart looping determination of bilateral symmetry epithelial tube morphogenesis embryonic organ development determination of left/right symmetry specification of symmetry embryonic organ morphogenesis heart development embryonic morphogenesis morphogenesis of an epithelium determination of heart left/right asymmetry tissue morphogenesis left/right pattern formation immune response-regulating cell surface receptor signaling pathway positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process immune response-activating cell surface receptor signaling pathway T cell receptor signaling pathway regulation of immune response antigen receptor-mediated signaling pathway activation of immune response immune system development gland development hematopoietic or lymphoid organ development thymus development myeloid leukocyte differentiation myeloid dendritic cell activation hemopoiesis mononuclear cell differentiation myeloid leukocyte activation myeloid cell differentiation myeloid dendritic cell differentiation dendritic cell differentiation leukocyte differentiation protein maturation protein processing negative regulation of neuron apoptotic process regulation of neuron apoptotic process limb development appendage development embryonic limb morphogenesis embryonic appendage morphogenesis appendage morphogenesis limb morphogenesis amyloid-beta formation regulation of receptor recycling receptor recycling receptor metabolic process positive regulation of receptor recycling positive regulation of signaling carbohydrate derivative biosynthetic process organonitrogen compound biosynthetic process glycoprotein biosynthetic process glycoprotein metabolic process protein glycosylation glycosylation macromolecule glycosylation locomotion Notch receptor processing smooth endoplasmic reticulum calcium ion homeostasis regulation of synaptic plasticity trans-synaptic signaling modulation of chemical synaptic transmission cell-cell signaling chemical synaptic transmission synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of RNA biosynthetic process positive regulation of phosphorylation positive regulation of protein modification process positive regulation of protein phosphorylation neuron migration cell adhesion cell-cell adhesion synaptic transmission, glutamatergic regulation of synaptic transmission, glutamatergic regulation of catalytic activity positive regulation of catalytic activity hematopoietic progenitor cell differentiation establishment of organelle localization regulated exocytosis synaptic vesicle targeting synaptic vesicle exocytosis vesicle targeting secretion by cell organelle localization signal release vesicle localization neurotransmitter secretion secretion establishment of vesicle localization export from cell neurotransmitter transport signal release from synapse exocytosis exocytic process post-embryonic development	membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope organelle nuclear envelope organelle membrane endoplasmic reticulum membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope organelle nuclear envelope organelle membrane endoplasmic reticulum smooth endoplasmic reticulum cytoplasm neuromuscular junction synapse cell junction Golgi membrane Golgi apparatus bounding membrane of organelle ciliary rootlet cilium plasma membrane bounded cell projection cell projection cytoskeleton intracellular non-membrane-bounded organelle non-membrane-bounded organelle transport vesicle intracellular vesicle presynapse cytoplasmic vesicle synaptic vesicle secretory vesicle vesicle exocytic vesicle mitochondrial membrane organelle inner membrane mitochondrion mitochondrial inner membrane mitochondrial envelope cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane cell surface membrane microdomain membrane raft protein-containing complex catalytic complex plasma membrane protein complex membrane protein complex gamma-secretase complex organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum membrane chromosome chromosomal region kinetochore chromosome, centromeric region condensed chromosome, centromeric region supramolecular complex condensed chromosome Z disc sarcomere I band contractile muscle fiber supramolecular fiber myofibril supramolecular polymer sarcolemma presynaptic membrane synaptic membrane glutamatergic synapse rough endoplasmic reticulum neuron projection vacuolar membrane lytic vacuole vacuole lytic vacuole membrane lysosomal membrane lysosome somatodendritic compartment dendrite dendritic tree dendritic shaft perinuclear region of cytoplasm cell body neuronal cell body postsynapse cell cortex centrosome microtubule organizing center microtubule cytoskeleton vesicle membrane azurophil granule cytoplasmic vesicle membrane secretory granule primary lysosome azurophil granule membrane secretory granule membrane growth cone axon distal axon site of polarized growth inclusion body aggresome membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen nuclear outer membrane organelle outer membrane outer membrane endosome membrane early endosome endosome early endosome membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR006639	Presenilin/signal peptide peptidase	Family
A	IPR002031	Peptidase A22A, presenilin 1	Family
A	IPR042524	Presenilin, C-terminal	Homologous Superfamily
A	IPR001108	Peptidase A22A, presenilin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P49768	Alzheimer disease amyloidosis Pick disease frontotemporal dementia dilated cardiomyopathy neurodegenerative disease dilated cardiomyopathy 1U perinatal asphyxia cardiomyopathy semantic dementia acne inversa, familial, 3 Hidradenitis suppurativa, familial Alzheimer disease 3 behavioral variant of frontotemporal dementia ovarian cancer Alzheimer disease amyloidosis Pick disease frontotemporal dementia dilated cardiomyopathy neurodegenerative disease dilated cardiomyopathy 1U perinatal asphyxia cardiomyopathy semantic dementia acne inversa, familial, 3 Hidradenitis suppurativa, familial Alzheimer disease 3 behavioral variant of frontotemporal dementia ovarian cancer depressive disorder dilated cardiomyopathy 1A Down syndrome familial isolated dilated cardiomyopathy subependymal giant cell astrocytoma adenoma juvenile dermatomyositis ulcerative colitis Parkinson disease progressive non-fluent aphasia acquired metabolic disease IgA glomerulonephritis toxic encephalopathy osteosarcoma dementia familial dilated cardiomyopathy progressive supranuclear palsy hidradenitis suppurativa intellectual disability tuberculosis learning disability Alzheimer disease 4 malignant mesothelioma

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.