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FLASH GENE
Symbol GZMB contributors: mct/npt - updated : 21-06-2017
HGNC name granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)
HGNC id 4709
Location 14q12      Physical location : 25.100.160 - 25.103.432
Synonym name
  • fragmentin 2
  • cathepsin G-like 1
  • T-cell serine protease 1-3E
  • cytotoxic T-lymphocyte proteinase 2
  • granzyme-2
    • Synonym symbol(s) CGL-1, CSPB, CTLA1, CTSGL1, CCPI, HLP, C11, GRB, SECT
    EC.number 3.4.21.79
    DNA
    TYPE functioning gene
    STRUCTURE 3.27 kb     5 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
    5 - 941 27.7 247 - 1991 1985927
    - - 997 - 235 - 1991 1985927
    - - - 66 - - 1991 1985927
    incapable of inducing apoptosis, but essentially identical proteolytic and cytotoxic properties to wild type GZMB
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach    
    Endocrinethyroid    
    Lymphoid/Immunespleen    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunenatural killer
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    		trypsin domain
    HOMOLOGY
    interspecies homolog to murine Gzmb
    intraspecies homolog to CTSG
    homolog to CMA1
    Homologene
    FAMILY
  • peptidase family S1
    • CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • serine protease necessary for target cell lysis in cell-mediated immune responses
  • critical role for GZMA and GZMB in dictating immunogenicity by influencing the mode of tumor cell death, indicating that granzymes contribute to the efficient generation of immune effector pathways in addition to their well-known role in apoptosis induction
  • inducing apoptosis of target cells in conjunction with perforin
  • role for granzyme B in the regulatory T cell compartment in immune regulation to viral infections
  • endogenous GZMB can play a promigratory role, at least in part through cleaving FGFR1
  • GZMB-mediated cleavage of fibronectin contributes to attenuated angiogenesis through the disruption of endothelial cell - fibronectin interaction resulting in impaired endothelial cell migration and tubular formation
  • from cytotoxic T lymphocyte (CTLS) acts double roles to keratinocytes: a IL18 converting enzyme and pro-apoptotic factor in the skin inflammatory diseases
  • is an immune-derived serine protease that accumulates in the extracellular matrix (ECM) during chronic inflammation and is capable of cleaving fibronectin (FN)
  • is a modulator of vascular response during chronic inflammation
  • GZMB-induced mitochondrial ROS are required for apoptosis
  • significant role for GZMB in Extracellular matrix (ECM) degradation that may have implications in many age-related chronic inflammatory diseases
  • is a protease with a well-characterized intracellular role in targeted destruction of compromised cells by cytotoxic lymphocytes
  • also cleaves extracellular matrix components, suggesting that it influences the interplay between cytotoxic lymphocytes and their environment
  • important role for GZMB in expediting cytotoxic lymphocyte diapedesis via basement membrane remodeling
  • is a serine protease involved in cell-mediated cytotoxicity in conjunction with the pore-forming protein, perforin
  • also likely contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process
  • perforin-independent, extracellular role for GZMB in the pathogenesis of cardiac fibrosis
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding mannose 6-phosphate IGFII receptor during cytotoxic T cell induced apoptosis
  • disables NOTCH1 function, probably resulting in anti-cellular proliferation and cell death signals
  • FGFR1 is a substrate for the serine protease GZMB
  • CUX1 is a substrate for GZMB and ubiquitination
  • is an important mediator of FCGR2A function in human monocytes
    • cell & other
    REGULATION
    activated by lymphokine activated killer (LAK) and natural killer (NK) cells (cathepsin G-like 1) (see SPAS@)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    are independently associated with insulin resistance and also with increased cardiovascular (CV) risk in adolescent polycystic ovary syndrome patients
    constitutional       loss of function
    diminished the ability of a high dose of CD8(+) T cells to cause lethal graft-versus-host disease
    Susceptibility to autism spectrum disorder
    Variant & Polymorphism
    Candidate gene
    Marker
  • both T2DM and central obesity were predicting factors for GZMB
    • Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    inhibiting donor-derived GzmB function may represent a promising strategy to improve GVT effect without exacerbating graft-versus-host disease
    ANIMAL & CELL MODELS
  • internalized killer cells from GzmB-deficient mice underwent a typical non-apoptotic entotic cell-in-cell death similar to that of non-cytotoxic immune cells or tumor cells