Seroatlas · Human Serome Atlas

PCSK4

Proprotein convertase subtilisin/kexin type 4

Also known as: DKFZp434B217, MGC34749, PC4, PCSK4_HUMAN, SPC5

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

Protein identityUniProt · HPA

UniProt accession
Q6UW60
Gene
PCSK4
Ensembl
ENSG00000115257
Chromosome
19
Canonical length
755 aa
Protein class
Enzymes, Predicted intracellular proteins, Predicted membrane proteins

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 encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

755 residues, UniProt reviewed canonical sequence.

>Q6UW60|PCSK4
     1  MRPAPIALWL RLVLALALVR PRAVGWAPVR APIYVSSWAV QVSQGNREVE RLARKFGFVN
    61  LGPIFPDGQY FHLRHRGVVQ QSLTPHWGHR LHLKKNPKVQ WFQQQTLQRR VKRSVVVPTD
   121  PWFSKQWYMN SEAQPDLSIL QAWSQGLSGQ GIVVSVLDDG IEKDHPDLWA NYDPLASYDF
   181  NDYDPDPQPR YTPSKENRHG TRCAGEVAAM ANNGFCGVGV AFNARIGGVR MLDGTITDVI
   241  EAQSLSLQPQ HIHIYSASWG PEDDGRTVDG PGILTREAFR RGVTKGRGGL GTLFIWASGN
   301  GGLHYDNCNC DGYTNSIHTL SVGSTTQQGR VPWYSEACAS TLTTTYSSGV ATDPQIVTTD
   361  LHHGCTDQHT GTSASAPLAA GMIALALEAN PFLTWRDMQH LVVRASKPAH LQAEDWRTNG
   421  VGRQVSHHYG YGLLDAGLLV DTARTWLPTQ PQRKCAVRVQ SRPTPILPLI YIRENVSACA
   481  GLHNSIRSLE HVQAQLTLSY SRRGDLEISL TSPMGTRSTL VAIRPLDVST EGYNNWVFMS
   541  THFWDENPQG VWTLGLENKG YYFNTGTLYR YTLLLYGTAE DMTARPTGPQ VTSSACVQRD
   601  TEGLCQACDG PAYILGQLCL AYCPPRFFNH TRLVTAGPGH TAAPALRVCS SCHASCYTCR
   661  GGSPRDCTSC PPSSTLDQQQ GSCMGPTTPD SRPRLRAAAC PHHRCPASAM VLSLLAVTLG
   721  GPVLCGMSMD LPLYAWLSRA RATPTKPQVW LPAGT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCSK4 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
Intracellular
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.3
Highest tissue expression
63 nTPM

Expression across tissuesHPA

Tissue

  • testis: 63 nTPM
  • pituitary gland: 6.6 nTPM
  • liver: 3.8 nTPM
  • kidney: 3.6 nTPM
  • hypothalamus: 3.3 nTPM
  • thyroid gland: 3.2 nTPM

Single-cell type

  • late spermatids: 1,192 nCPM
  • late primary spermatocytes: 289 nCPM
  • early spermatids: 289 nCPM
  • ependymal cells: 39 nCPM
  • early primary spermatocytes: 34 nCPM
  • oocytes: 23 nCPM

Immune cell

  • plasmacytoid DC: 0.3 nTPM
  • naive CD4 T-cell: 0.1 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM

Brain region

  • midbrain: 6.7 nTPM
  • medulla oblongata: 4.7 nTPM
  • spinal cord: 4.4 nTPM
  • hypothalamus: 4.1 nTPM
  • thalamus: 3.8 nTPM
  • pons: 3.7 nTPM

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)
0.96
gnomAD pLI
0
gnomAD missense Z
-0.04
DepMap mean gene effect
0.09
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% 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 PCSK4 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 PCSK4 as an antibody target. Whether an autoantibody or antibody against PCSK4 could matter depends on whether native PCSK4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PCSK4 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 PCSK4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/PCSK4. 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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