Seroatlas · Human Serome Atlas

PSEN1

Presenilin-1

Also known as: AD3, FAD, PS1, PSN1_HUMAN, S182

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P49768
Gene
PSEN1
Ensembl
ENSG00000080815
Chromosome
14
Canonical length
467 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Nucleoplasm,Golgi apparatus,Cell Junctions
Quaternary structure
Homodimer

OverviewNCBI Gene

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]

Canonical amino-acid sequenceUniProt

467 residues, UniProt reviewed canonical sequence.

>P49768|PSEN1
     1  MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR
    61  QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE
   121  DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI
   181  YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY
   241  LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE
   301  GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA
   361  VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL
   421  TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PSEN1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
9
Mean surface accessibility (rSASA)
0.4
Highest tissue expression
79 nTPM

Expression across tissuesHPA

Tissue

  • spinal cord: 79 nTPM
  • small intestine: 39 nTPM
  • midbrain: 38 nTPM
  • duodenum: 38 nTPM
  • colon: 35 nTPM
  • hippocampal formation: 34 nTPM

Single-cell type

  • neutrophils: 2,031 nCPM
  • neutrophil progenitors: 647 nCPM
  • oligodendrocytes: 545 nCPM
  • monocytes: 480 nCPM
  • enterocytes: 259 nCPM
  • colonocytes: 233 nCPM

Immune cell

  • non-classical monocyte: 110 nTPM
  • neutrophil: 103 nTPM
  • basophil: 98 nTPM
  • intermediate monocyte: 94 nTPM
  • classical monocyte: 83 nTPM
  • eosinophil: 83 nTPM

Brain region

  • white matter: 60 nTPM
  • basal ganglia: 49 nTPM
  • medulla oblongata: 46 nTPM
  • cerebellum: 43 nTPM
  • midbrain: 38 nTPM
  • spinal cord: 37 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PSEN1.

Disease | AllUniProt

Conditions PSEN1 is implicated in, by any mechanism.

Disease | GeneticClinVar

149 pathogenic / likely-pathogenic of 624 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

ReferencesPubMed · IEDB

Publications for PSEN1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

1 publication

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.32
gnomAD pLI
0.97
gnomAD missense Z
2.16
DepMap mean gene effect
-0.04
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PSEN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PSEN1 as an antibody target. Whether an autoantibody or antibody against PSEN1 could matter depends on whether native PSEN1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PSEN1 is annotated at the cell surface, where native PSEN1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label PSEN1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/PSEN1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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