Seroatlas · Human Serome Atlas

PSEN2

Presenilin-2

Also known as: AD3L, AD4, PS2, PSN2_HUMAN, STM2

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

Protein identityUniProt · HPA

UniProt accession
P49810
Gene
PSEN2
Ensembl
ENSG00000143801
Chromosome
1
Canonical length
448 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters
Quaternary structure
Homodimer

OverviewNCBI Gene

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or 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 act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

448 residues, UniProt reviewed canonical sequence.

>P49810|PSEN2
     1  MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ ENEEDGEEDP
    61  DRYVCSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI
   121  YTPFTEDTPS VGQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL
   181  FLFTYIYLGE VLKTYNVAMD YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA
   241  LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
   301  TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE ELEEEEERGV
   361  KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI
   421  TFGLIFYFST DNLVRPFMDT LASHQLYI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PSEN2 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
Other membrane
Secreted
No
Transmembrane segments
8
Mean surface accessibility (rSASA)
0.41
Highest tissue expression
34 nTPM

Expression across tissuesHPA

Tissue

  • pancreas: 34 nTPM
  • skeletal muscle: 25 nTPM
  • choroid plexus: 17 nTPM
  • parathyroid gland: 17 nTPM
  • tongue: 16 nTPM
  • adrenal gland: 15 nTPM

Single-cell type

  • renal collecting duct intercalated cells: 21 nCPM
  • other brain neurons: 12 nCPM
  • podocytes: 8.3 nCPM
  • brain inhibitory neurons: 7.8 nCPM
  • brain excitatory neurons: 7.7 nCPM
  • choroid plexus epithelial cells: 7.4 nCPM

Immune cell

  • basophil: 38 nTPM
  • non-classical monocyte: 31 nTPM
  • NK-cell: 20 nTPM
  • eosinophil: 19 nTPM
  • myeloid DC: 11 nTPM
  • intermediate monocyte: 9.8 nTPM

Brain region

  • cerebellum: 24 nTPM
  • midbrain: 22 nTPM
  • choroid plexus: 21 nTPM
  • pons: 21 nTPM
  • hypothalamus: 21 nTPM
  • cerebral cortex: 20 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PSEN2.

Disease | AllUniProt

Conditions PSEN2 is implicated in, by any mechanism.

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 367 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Alzheimer disease 4

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)
0.74
gnomAD pLI
0
gnomAD missense Z
0.4
DepMap mean gene effect
0.03
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% 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 PSEN2 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 PSEN2 as an antibody target. Whether an autoantibody or antibody against PSEN2 could matter depends on whether native PSEN2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PSEN2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label PSEN2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/PSEN2. 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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