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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
Corresponding disease
BDIAS Blue diaper syndrome
OBS10 extreme obesity with a defective prohormone processing
Location 5q15      Physical location : 95.726.039 - 95.768.985
Synonym name
  • neuroendocrine convertase 1,protein convertase 1/3
  • Synonym symbol(s) NEC1, PC1, PC3, SKI1, PCSK, BMIQ12, SPC3
    EC.number 3.4.21.93
    DNA
    TYPE functioning gene
    STRUCTURE 42.92 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    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
  • 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
    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