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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
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