Seroatlas · Human Serome Atlas

PCSK2

Neuroendocrine convertase 2

Also known as: NEC2, NEC2_HUMAN, PC2, SPC2

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

Protein identityUniProt · HPA

UniProt accession
P16519
Gene
PCSK2
Ensembl
ENSG00000125851
Chromosome
20
Canonical length
638 aa
Protein class
Enzymes, Predicted intracellular proteins, Predicted secreted proteins
Subcellular location
Vesicles
Secretome location
Secreted in other tissues

OverviewNCBI Gene

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

638 residues, UniProt reviewed canonical sequence.

>P16519|PCSK2
     1  MKGGCVSQWK AAAGFLFCVM VFASAERPVF TNHFLVELHK GGEDKARQVA AEHGFGVRKL
    61  PFAEGLYHFY HNGLAKAKRR RSLHHKQQLE RDPRVKMALQ QEGFDRKKRG YRDINEIDIN
   121  MNDPLFTKQW YLINTGQADG TPGLDLNVAE AWELGYTGKG VTIGIMDDGI DYLHPDLASN
   181  YNAEASYDFS SNDPYPYPRY TDDWFNSHGT RCAGEVSAAA NNNICGVGVA YNSKVAGIRM
   241  LDQPFMTDII EASSISHMPQ LIDIYSASWG PTDNGKTVDG PRELTLQAMA DGVNKGRGGK
   301  GSIYVWASGD GGSYDDCNCD GYASSMWTIS INSAINDGRT ALYDESCSST LASTFSNGRK
   361  RNPEAGVATT DLYGNCTLRH SGTSAAAPEA AGVFALALEA NLGLTWRDMQ HLTVLTSKRN
   421  QLHDEVHQWR RNGVGLEFNH LFGYGVLDAG AMVKMAKDWK TVPERFHCVG GSVQDPEKIP
   481  STGKLVLTLT TDACEGKENF VRYLEHVQAV ITVNATRRGD LNINMTSPMG TKSILLSRRP
   541  RDDDSKVGFD KWPFMTTHTW GEDARGTWTL ELGFVGSAPQ KGVLKEWTLM LHGTQSAPYI
   601  DQVVRDYQSK LAMSKKEELE EELDEAVERS LKSILNKN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCSK2 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
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.24
Highest tissue expression
54 nTPM

Expression across tissuesHPA

Tissue

  • thyroid gland: 54 nTPM
  • retina: 33 nTPM
  • adrenal gland: 27 nTPM
  • cerebral cortex: 21 nTPM
  • pancreas: 19 nTPM
  • skin: 13 nTPM

Single-cell type

  • müller glia: 903 nCPM
  • pancreatic islet cells: 903 nCPM
  • adrenal medulla cells: 883 nCPM
  • melanocytes: 451 nCPM
  • retinal horizontal cells: 321 nCPM
  • brain excitatory neurons: 315 nCPM

Immune cell

  • basophil: 0.5 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • cerebral cortex: 109 nTPM
  • white matter: 68 nTPM
  • hypothalamus: 64 nTPM
  • thalamus: 62 nTPM
  • hippocampal formation: 57 nTPM
  • amygdala: 55 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PCSK2.

Disease | ImmuneIEDB

Conditions an epitope on PCSK2 was assayed in.

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)
0.24
gnomAD pLI
1
gnomAD missense Z
3.55
DepMap mean gene effect
0.1
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PCSK2 as an antibody target. Whether an autoantibody or antibody against PCSK2 could matter depends on whether native PCSK2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PCSK2 is annotated as secreted, so native PCSK2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label PCSK2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/PCSK2. 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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