InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PSEN1

Summary

InnateDB Protein

IDBP-11241.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PSEN1

Protein Name

presenilin 1

Synonyms

AD3; FAD; PS-1; PS1; S182;

Species

Homo sapiens

Ensembl Protein

ENSP00000326366

InnateDB Gene

IDBG-11235 (PSEN1)

Protein Structure

UniProt Annotation

Function

Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis. {ECO:0000269PubMed:10206644, ECO:0000269PubMed:10545183, ECO:0000269PubMed:10593990, ECO:0000269PubMed:10811883, ECO:0000269PubMed:10899933, ECO:0000269PubMed:11226248, ECO:0000269PubMed:15341515, ECO:0000269PubMed:16305624}.

Subcellular Localization

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell surface. Note=Bound to NOTCH1 also at the cell surface. Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane. Also present in azurophil granules of neutrophils.

Disease Associations

Alzheimer disease 3 (AD3) [MIM:607822]: A familial early- onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. {ECO:0000269PubMed:10025789, ECO:0000269PubMed:10090481, ECO:0000269PubMed:10200054, ECO:0000269PubMed:10208579, ECO:0000269PubMed:10439444, ECO:0000269PubMed:10441572, ECO:0000269PubMed:10447269, ECO:0000269PubMed:10533070, ECO:0000269PubMed:10631141, ECO:0000269PubMed:10644793, ECO:0000269PubMed:11027672, ECO:0000269PubMed:11710891, ECO:0000269PubMed:11920851, ECO:0000269PubMed:12048239, ECO:0000269PubMed:12484344, ECO:0000269PubMed:12493737, ECO:0000269PubMed:22503161, ECO:0000269PubMed:7550356, ECO:0000269PubMed:7596406, ECO:0000269PubMed:7651536, ECO:0000269PubMed:8634711, ECO:0000269PubMed:8634712, ECO:0000269PubMed:8733303, ECO:0000269PubMed:9172170, ECO:0000269PubMed:9225696, ECO:0000269PubMed:9298817, ECO:0000269PubMed:9384602, ECO:0000269PubMed:9507958, ECO:0000269PubMed:9521423, ECO:0000269PubMed:9719376, ECO:0000269PubMed:9831473, ECO:0000269PubMed:9833068, ECO:0000269Ref.77}. Note=The disease is caused by mutations affecting the gene represented in this entry.Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269PubMed:11094121}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiomyopathy, dilated 1U (CMD1U) [MIM:613694]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269PubMed:17186461}. Note=The disease is caused by mutations affecting the gene represented in this entry.Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269PubMed:20929727}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes. {ECO:0000269PubMed:11987239, ECO:0000269PubMed:8574969}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 157 experimentally validated interaction(s) in this database.
They are also associated with 25 interaction(s) predicted by orthology.

Experimentally validated
Total	157 [view]
Protein-Protein	153 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	25 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004175	endopeptidase activity
GO:0004190	aspartic-type endopeptidase activity
GO:0005262	calcium channel activity
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008233	peptidase activity
GO:0030165	PDZ domain binding
GO:0045296	cadherin binding

Biological Process

GO:0000045	autophagic vacuole assembly
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000186	activation of MAPKK activity
GO:0001568	blood vessel development
GO:0001708	cell fate specification
GO:0001756	somitogenesis
GO:0001764	neuron migration
GO:0001921	positive regulation of receptor recycling
GO:0001933	negative regulation of protein phosphorylation
GO:0001934	positive regulation of protein phosphorylation
GO:0001947	heart looping
GO:0002244	hematopoietic progenitor cell differentiation
GO:0002286	T cell activation involved in immune response
GO:0002573	myeloid leukocyte differentiation
GO:0006469	negative regulation of protein kinase activity
GO:0006486	protein glycosylation
GO:0006508	proteolysis
GO:0006509	membrane protein ectodomain proteolysis
GO:0006839	mitochondrial transport
GO:0006874	cellular calcium ion homeostasis
GO:0006914	autophagy
GO:0006974	cellular response to DNA damage stimulus
GO:0006979	response to oxidative stress
GO:0007175	negative regulation of epidermal growth factor-activated receptor activity
GO:0007176	regulation of epidermal growth factor-activated receptor activity
GO:0007219	Notch signaling pathway
GO:0007220	Notch receptor processing
GO:0007420	brain development
GO:0007507	heart development
GO:0007611	learning or memory
GO:0007613	memory
GO:0009791	post-embryonic development
GO:0015031	protein transport
GO:0015813	L-glutamate transport
GO:0015871	choline transport
GO:0016080	synaptic vesicle targeting
GO:0016337	single organismal cell-cell adhesion
GO:0016485	protein processing
GO:0021795	cerebral cortex cell migration
GO:0021870	Cajal-Retzius cell differentiation
GO:0021904	dorsal/ventral neural tube patterning
GO:0021987	cerebral cortex development
GO:0022008	neurogenesis
GO:0022617	extracellular matrix disassembly
GO:0030182	neuron differentiation
GO:0030198	extracellular matrix organization
GO:0030326	embryonic limb morphogenesis
GO:0030900	forebrain development
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032469	endoplasmic reticulum calcium ion homeostasis
GO:0034205	beta-amyloid formation
GO:0035282	segmentation
GO:0035556	intracellular signal transduction
GO:0040011	locomotion
GO:0042325	regulation of phosphorylation
GO:0042640	anagen
GO:0042987	amyloid precursor protein catabolic process
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043085	positive regulation of catalytic activity
GO:0043393	regulation of protein binding
GO:0043406	positive regulation of MAP kinase activity
GO:0043524	negative regulation of neuron apoptotic process
GO:0043589	skin morphogenesis
GO:0044267	cellular protein metabolic process
GO:0045860	positive regulation of protein kinase activity
GO:0048167	regulation of synaptic plasticity
GO:0048538	thymus development
GO:0048666	neuron development
GO:0048705	skeletal system morphogenesis
GO:0048854	brain morphogenesis
GO:0050435	beta-amyloid metabolic process
GO:0050673	epithelial cell proliferation
GO:0050771	negative regulation of axonogenesis
GO:0050820	positive regulation of coagulation
GO:0050852	T cell receptor signaling pathway
GO:0051402	neuron apoptotic process
GO:0051444	negative regulation of ubiquitin-protein transferase activity
GO:0051563	smooth endoplasmic reticulum calcium ion homeostasis
GO:0051604	protein maturation
GO:0051966	regulation of synaptic transmission, glutamatergic
GO:0060070	canonical Wnt signaling pathway
GO:0060075	regulation of resting membrane potential
GO:0070588	calcium ion transmembrane transport
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2001234	negative regulation of apoptotic signaling pathway

Cellular Component

GO:0000139	Golgi membrane
GO:0000776	kinetochore
GO:0005622	intracellular
GO:0005634	nucleus
GO:0005640	nuclear outer membrane
GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005765	lysosomal membrane
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005790	smooth endoplasmic reticulum
GO:0005791	rough endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005813	centrosome
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005938	cell cortex
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016324	apical plasma membrane
GO:0030018	Z disc
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0031410	cytoplasmic vesicle
GO:0031594	neuromuscular junction
GO:0031965	nuclear membrane
GO:0035253	ciliary rootlet
GO:0043005	neuron projection
GO:0043025	neuronal cell body
GO:0043198	dendritic shaft
GO:0043227	membrane-bounded organelle
GO:0043234	protein complex
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm
GO:0070765	gamma-secretase complex