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FLASH GENE
Symbol PCSK1 contributors: mct - updated : 12-06-2020
HGNC name proprotein convertase subtilisin/kexin type 1
HGNC id 8743
RNA
TRANSCRIPTS type messenger
text multiple alternatively spliced transcript variants
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 5136 - 753 - 2016 28271036
14 - 4824 - 706 - 2016 28271036
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
 pancreas   highly
nervousbraindiencephalon   
Nervousnervespinal nervesciatic  
Visualeyeretina   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Epithelialsecretoryglandularendocrine 
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a preprodomain, a subtilisin-like catalytic, serine protease domain Ca2+ dependent,
  • conserved P(hemo B) domain,
  • a furin cysteine-rich region,
  • a transmembrane anchor and a cytoplasmic domain
  • C-terminus translocated across the endoplasmic reticulum membrane
  • isoforms Precursor autocatalytically activated
    HOMOLOGY
    Homologene
    FAMILY
  • proprotein convertase subtilisin kexin-like (SPC) subtilase family
  • mammalian subtilisin-like proprotein convertase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    text
  • secretory granules
  • its propeptide is rapidly and autocatalytically cleaved in the endoplasmic reticulum; the mature protein is sorted and stored in dense-core secretory vesicles, together with its substrates
  • basic FUNCTION
  • endopeptidase involved in proteolytic processing of peptide hormone precursors in granules of the regulated secretory pathway of endocrine cells
  • specifically cleaving BDNF, processing of hormones and other proteins
  • type I proinsulin-processing enzyme that plays a key role in regulating insulin biosynthesis
  • involved in the endoproteolytic cleavage of a large number of precursor proteins including prohormones, proneuropeptides, zymogens, and proreceptors
  • is a serine endoprotease that is involved in the processing of a variety of proneuropeptides and prohormones
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
  • NHLH2 has been shown to promote PCSK1 expression
  • ANGPTL4 promotes PCSK1-mediated intracellular cleavage of LPL in adipocytes, likely contributing to regulation of LPL in adipose tissue
  • cell & other
    REGULATION
    activated by upregulated during early phase of liver regeneration
    ASSOCIATED DISORDERS
    corresponding disease(s) OBS10 , BDIAS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    decreased hypothalamic PCSK1, PCSK2, FURIN in huntington disease patients
    constitutional       loss of function
    impairs prohormone processing in Prader-Willi syndrome
    Susceptibility
  • to non insulin dependent diabetes (type II) and coronary artery disease
  • to obesity
  • to hypertension
  • Variant & Polymorphism other
  • N221D, and Q665E-S690T pair, associated with obesity in adults and children
  • more common variants in the PCSK1 gene have been found to be associated with alterations in body mass index, increased circulating proinsulin levels, and defects in glucose homeostasis
  • association of genetic variation in the PCSK1 gene with blood pressure and hypertension
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS