Seroatlas · Human Serome Atlas

APP

Amyloid-beta precursor protein

Also known as: A4_HUMAN, AD1, alpha-sAPP

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

Protein identityUniProt · HPA

UniProt accession
P05067
Gene
APP
Ensembl
ENSG00000142192
Chromosome
21
Canonical length
770 aa
Protein class
Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters
Subcellular location
Golgi apparatus,Vesicles
Secretome location
Secreted to blood
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]

Canonical amino-acid sequenceUniProt

770 residues, UniProt reviewed canonical sequence.

>P05067|APP
     1  MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
    61  TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
   121  EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
   181  GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
   241  EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
   301  RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
   361  PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
   421  KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
   481  QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
   541  MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
   601  KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
   661  IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL
   721  VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against APP 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
1
Mean surface accessibility (rSASA)
0.47
Highest tissue expression
669 nTPM

Expression across tissuesHPA

Tissue

  • cerebral cortex: 669 nTPM
  • spinal cord: 536 nTPM
  • hippocampal formation: 467 nTPM
  • kidney: 465 nTPM
  • basal ganglia: 458 nTPM
  • midbrain: 449 nTPM

Single-cell type

  • lymphatic endothelial cells: 1,231 nCPM
  • oligodendrocytes: 1,026 nCPM
  • syncytiotrophoblasts: 977 nCPM
  • pdcs: 960 nCPM
  • retinal pigment epithelial cells: 874 nCPM
  • vascular endothelial cells: 850 nCPM

Immune cell

  • plasmacytoid DC: 36 nTPM
  • classical monocyte: 7.5 nTPM
  • myeloid DC: 5.6 nTPM
  • total PBMC: 3.2 nTPM
  • naive CD4 T-cell: 2.3 nTPM
  • memory CD4 T-cell: 2.2 nTPM

Brain region

  • white matter: 921 nTPM
  • midbrain: 879 nTPM
  • cerebral cortex: 851 nTPM
  • pons: 789 nTPM
  • thalamus: 748 nTPM
  • basal ganglia: 742 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about APP.

Disease | AllUniProt

Conditions APP is implicated in, by any mechanism.

Disease | GeneticClinVar

28 pathogenic / likely-pathogenic of 629 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on APP was assayed in.

ReferencesPubMed · IEDB

Publications for APP 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

2 publications

Reference: B cellIEDB

29 publications

Show 20 more of 29 total

Reference: T cellIEDB

11 publications

Show 6 more

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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)
0.42
gnomAD pLI
0.05
gnomAD missense Z
1.39
DepMap mean gene effect
0.06
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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 APP 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 APP as an antibody target. Whether an autoantibody or antibody against APP could matter depends on whether native APP is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

APP is annotated at the cell surface, where native APP 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 APP as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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