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FLASH GENE
Symbol SERPINB2 contributors: mct - updated : 13-11-2024
HGNC name serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2
HGNC id 8584
Location 18q21.33      Physical location : 61.554.938 - 61.571.120
Synonym name
  • DNA segment, single copy, probe A24L
  • plasminogen activator inhibitor, type II (arginine-serpin)
  • placental plasminogen activator inhibitor
  • urokinase inhibitor
    • Synonym symbol(s) PLANH2, PAI, PAI2, PAI-2, HsT1201
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 16.19 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer
    text structure
  • a silencer PAUSE-1 in the promoter region, directing an active mechanism of transcriptional repression
  • promoter is controlled by three major transcription regulatory domains: an inducible proximal promoter, an upstream silencer (PAUSE-1), and a distal transactivator region between -5100 and -3300, which appears to overcome inhibition mediated by the silencer
  • promoter contains several AP-1 or AP-1-like consensus sequences, however, their presence does not automatically imply functionality in a given gene promoter
    • MAPPING cloned Y linked N status confirmed
    Map cen - D18S18 - SERPINB4 - [D18S38 - D18S60 - D18S51 /SERPINB2 - D18S68 - SERPINB5 - D18S42 - D18S14 - D18S55 ] - SERPINB3 - TGFBRE - D18S485 - D18S61 - qter
    Authors Schneider (95), LDB, Katz (99)
    Text [deletion in 18QDCR ]
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 2180 - 415 - 2013 2347408
    8 - 1922 43 415 - 2013 2347408
  • secreted SERPINB2 was predominantly in its nonglycosylated 43kDa form
    		•
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemplacenta   
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines tumor cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta, trophoblasts
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY clade B family of serine protease inhibitors
    CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • delivered to the plasma membrane, apparently together with TGOLN2 in the same vesicles, which after fusion with the membranes released cargo
  • predominant cytoplasmic localisation
    • basic FUNCTION
  • serine proteinase inhibitor
  • plasminogen activator inhibitor type 2
  • inhibit extracellular matrix degradation by PLAU (urokinase inhibitor)
  • regulation of Th1 responses appears to be a physiological function of inflammation-associated SERPINB2
  • enzyme inhibitor which is involved in various biological processes including cell differentiation, tissue regrowth and regeneration
  • has a role for promoting the differentiation of epidermal keratinocytes
  • in endothelial cells SERPINB2 induced with inflammatory stimuli, can inhibit proteasome and thus tilt the balance favoring proapoptotic signaling
  • its extracellular concentration significantly increases during inflammation
  • SERPINB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa
  • display cytoprotective properties in neurons and interact with intracellular proteins including components of the ubiquitin-proteasome system (UPS)
  • plays an important role in proteostasis as its loss leads to a proteotoxic phenotype associated with an inability to compartmentalize aggregating proteins and a reduced capacity of the UPS
  • novel role for SERPINB2 in the stromal compartment in pancreatic ductal adenocarcinoma (PDAC) invasion through regulation of stromal remodelling
  • is an inhibitor of fibrinolysis, and is likely associated with platelet aggregates
  • role of SERPINB2 in macrophages is inhibition of PLAU-mediated plasmin generation during cell migration
  • influences tubule-macrophage crosstalk by supporting tubular CCL2 expression and regulating macrophage phagocytosis and migration
  • possible involvement of SERPINB2 in physiological mineralization
  • potentially contributes to controlling aberrant fibrinolysis and the accumulation of misfolded proteins in states characterised by oxidative and proteostasis stress, such as in Alzheimer's disease and preeclampsia
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text protecting hematopoietic cells and keratinocytes from inappropriatly timed apoptosis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • potent inhibitor of urokinase-type plasminogen activator (PLAU) and also acts as a multifunctional protein
  • physiological interaction between RB1, RBL2 and SERPINB2
  • is a cell survival factor that modulates RB1 repression of proapoptotic signal transduction
  • while SERPINE1 and SERPINB2 function similarly in the control of cellular plasmin generation by PLAT, they may have disparate effects on the alternative functions of PLAT via modulation of its engagement with endocytosis receptors
  • interacts with proteasome and affects its activity in endothelial cells
  • SERPINB2 and TGM2 are downstream mediators in the antiapoptotic response triggered upon TBK1 activation
  • FOSB is the mediator of SERPINB2 transactivator function explaining the orientation dependence observed for SERPINB2 transactivator activity
  • FOSB and JUN can derepress transcription from the SERPINB2 promoter which may have general significance for SERPINB2-expressing cells
  • PSMB1 is part of the transcriptional machinery required for gastrin stimulated expression of SERPINB2 and REG1A, and its change in subcellular distribution in response to gastrin is consistent with this role
  • extracellular matrix-associated proteins vitronectin and plasminogen activator inhibitor-2 (SERPINB2) were identified as novel CHL1 interaction partners, promoting CHL1-induced neurite outgrowth and neuronal migration
  • SERPINB2 is a direct downstream target of TP53 that is activated by the DNA damage response pathway
  • SERPINB2 silencing promoted osteogenic differentiation of bone marrow mesenchymal stem cells via the WNT/CTNNB signaling pathway
    • cell & other
    REGULATION
    induced by high levels of expression after stimulation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in oral squamous cell carcinomas
    tumoral   deletion    
    frequently deleted in pancreatic ductal adenocarcinoma (PDAC)
    constitutional     --over  
    significantly increased in response to various toxic agents in human stem cells
    constitutional     --over  
    during pregnancy and in response to inflammation
    Susceptibility to myocardial infarction
    Variant & Polymorphism SNP
    Candidate gene
    Marker
  • SERPINB2 is considered as a senescence biomarker
    • Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    SERPINB2 may be a novel target for bone fracture healing
    ANIMAL & CELL MODELS
  • in mice, SerpinB2 expression seems to be needed for coordination and timely resolution of inflammation, successful repair, and kidney homeostasis during aging