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FLASH GENE
Symbol FURIN contributors: mct - updated : 29-11-2014
HGNC name furin (paired basic amino acid cleaving enzyme)
HGNC id 8568
Location 15q26.1      Physical location : 91.411.884 - 91.426.687
Synonym name
  • proprotein convertase subtilisin/kexin type 3
  • FES upstream region
  • proprotein convertase subtilisin/kexin type 3
  • paired basic amino acid cleaving enzyme (furin, membrane associated receptor
    • protein)
  • dibasic-processing enzyme
  • furin, membrane associated receptor protein
    • Synonym symbol(s) FUR, PCSK3, SPC1, PACE
    EC.number 3.4.21.75
    DNA
    TYPE functioning gene
    STRUCTURE 15.17 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 4180 - 794 - 2006 16942750
  • preproprotein
    • - - 4198 - 794 - 2006 16942750
    - - 4352 - 794 - 2006 16942750
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     liver   highly
    Endocrinepancreas   highly
    Reproductivefemale systemplacenta  highly Homo sapiens
     male systemtestis  lowly
    Respiratorylung   lowly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac lowly
    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 an (hemo B) domain
  • a cysteine-rich region
  • a transmembrane anchor and a cytoplasmic domain
    • conjugated GlycoP , PhosphoP
    isoforms Precursor autocatalytically activated
    HOMOLOGY
    interspecies homolog to murine Furin (93.9pc)
    homolog to rattus Furin (93.8pc)
    intraspecies homolog to PCSK5,PCSK4
    Homologene
    FAMILY
  • subtilisin-like proprotein convertase family
  • peptidase S8 family
  • furin subfamily
    • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    text
  • membrane associated protein circulating between the trans-Golgi network and cell surface
  • highly expressed in syncytial trophoblast in the first trimester human placenta
    • basic FUNCTION
  • paired basic amino-acid residue cleaving enzyme
  • involved in processing of pro-parathyroid hormone, von Willebrand factor, insulin receptor, TGF1B, hepatocyte growth factor, C propeptide of collagen type V, alpha 1, NOTCH signaling proteins, certain viral enveloppe glycoproteins, ED1
  • protease
  • cleaving CD109 and thus involved in the regulation of TGF-beta signaling
  • may be responsible for the activation of HIV envelope glycoproteins gp160 and gp140
  • may play a role in tumor progression
  • cleaving hemojuvelin
  • mediating the posttranslational processing of hepcidin
  • proprotein convertase that cycles between the plasma membrane, endosomes and the trans-Golgi network (TGN), maintaining a predominant distribution in the latter
  • involved in the signaling and trafficking of membrane proteins
  • may control hepcidin expression
  • SRC and FURIN play crucial roles in tumorigenesis
  • FURIN function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development
  • is the primary convertase of ANGPTL3 and endothelial lipase in hepatocytes
  • FURIN, PCSK5, and PCSK6 process two triglyceride lipase family members, endothelial lipase and lipoprotein lipase, which are important for HDL remodeling
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS development
    text required for ventral closure and axial rotation
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • binding to PACS1 which mediates its TGN localization and connection to clathrin adapters
  • interacting with FLNA
  • interacting with TFR2 and HFE (TFR2 and HFE are involved in holotransferrin-dependent signaling for the regulation of FURIN which involved Erk phosphorylation)
  • interaction between the PTB domain of APBA3 and the acidic peptide signal of FURIN regulates the specific localization of FURIN in the TGN
  • important role for FURIN in regulated secretion, particularly in intragranular acidification most likely due to impaired processing of ATP6AP1
  • MMP14 and FURIN were found to co-localize with Golgi reassembly stacking protein 55 (GORASP2)
  • SERPINE1 is an intracellular inhibitor of furin, having an active role in the development of metabolic disorders
  • association between FURIN and MMP14 is regulated by the tyrosine kinase SRC
  • NOTCH1-FURIN interaction is regulated by the non-receptor tyrosine kinase, SRC
  • PCSK3/FURIN was identified as the major proprotein convertase expressed by adipocytes that mediates the endogenous cleavage of C1QTNF12
  • SERPINE2 inhibits FURIN, a serine protease that activates MMP17 involved in the shedding of endothelial PROCR, suggesting a direct interaction between SERPINE2 and FURIN in endothelial cells
  • PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
  • FURIN appears to be the essential enzyme for the generation of kisspeptin (KISS1)
    • cell & other
    REGULATION
    induced by leukotriene D4
    inhibited by the not secondly cleaved propeptide
    Other up-regulated by TGFB1
    oxidation by H2O2 disrupts its Ca2+-binding capacity in vitiligo
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    no expression in small cell lung cancers
    tumoral     --over  
    overexpressed in non small cell lung cancers
    constitutional     --low  
    decreased hypothalamic PCSK1, PCSK2, FURIN in huntington disease patients
    constitutional     --low  
    in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas
    Susceptibility to (PACE) insulin-resistent diabetes (INSR), hemophilia B (F9) and Marfan syndrome (FBN1)
    Variant & Polymorphism SNP
  • SNP in the P1 promoter of FURIN affects furin transcription activity and hepatitis B virus infection outcome
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    mutant-/- embryomic lethal,failing to undergo looping and embryonic turning