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FLASH GENE
Symbol GLRX3 contributors: mct - updated : 21-11-2019
HGNC name glutaredoxin 3
HGNC id 15987
Location 10q26.3      Physical location : 131.934.662 - 131.977.870
Synonym name
  • PKC-interacting cousin of thioredoxin
  • thioredoxin-like 2
  • glutaredoxin 4
  • PKC-theta-interacting protein
  • PKCq-interacting protein
  • protein kinase C-interacting cousin of thioredoxin
    • Synonym symbol(s) PICOT, bA500G10.4, GRX3, GLRX4, GRX4, TXNL2, FLJ11864, TXNL3
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 46.50 kb     11 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1274 37 335 - 2019 30595380
    12 - 1365 - 335 - 2019 30595380
    12 - 1385 - 189 - 2019 30595380
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Digestiveliver    
    Reproductivefemale systemuteruscervix highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose  highly
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal tioredoxin homology domain
  • two tandem repeats of a domain highly conserved from plants to mammals
  • a carboxy-terminal tandem repeat of a monothiol glutaredoxin-like domain
    • conjugated MetalloP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Txnl2
    Homologene
    FAMILY
  • thioredoxin family
    • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • colocalizes with CSRP3 in the Z-disc
  • predominant cytosolic staining of epithelial cells and low or undetectable levels of GLRX3 in the stroma
  • predominantly localized in the cytoplasm under normal growth conditions, whereas under oxidizing conditions, GLRX3 is translocated into and accumulated in the nucleus
    • basic FUNCTION
  • regulator of thioderoxin system
  • may act as an endogenous negative feedback regulator of cardiac hypertrophy through its ability to inhibit PKC activity, which is elevated during cardiac hypertrophy
  • inhibiting cardiac remodeling by with a concomitant increase in ventricular function and cardiomyocyte contractility
  • inhibit pressure overload-induced cardiac hypertrophy, concomitant with an increase in ventricular function and cardiomyocyte contractility
  • inhibits cardiac hypertrophy largely by negatively regulating calcineurin-NFAT signaling via disruption of the CSRP3-calcineurin interaction
  • protein invovled in the regulation of signal transduction
  • is an essential [2Fe-2S]-binding protein with ill-defined roles in immune cell response, embryogenesis, cancer cell growth, and regulation of cardiac hypertrophy
  • multi-domain mono-thiol glutaredoxin that is involved in several signal transduction pathways and is necessary for cell growth and metastasis
  • possibility that the pro-apoptotic role of GLRX3 is actively regulated via CASP3-mediated cleavage
  • evolutionarily conserved role of cytosolic monothiol multidomain glutaredoxins in cellular iron metabolism pathways, including the biogenesis of Fe/S proteins and hemoglobin maturation
  • critical in maintaining redox homeostasis and regulating cell survival pathways in cancer cells
  • important for regulating cellular redox homeostasis in the cell
  • is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS
  • involved in the regulation of signal transduction in T lymphocytes and cardiac muscle, and in cellular iron metabolism and biogenesis of Fe/S proteins
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • iron-sulfur protein
  • apo BOLA2 binds to each Grx domain in the [2Fe-2S] GLRX3 homodimer forming a [2Fe-2S] BOLA2-GLRX3 heterotrimer
  • monothiol glutaredoxin GLRX3 and BOlA2 function as a [2Fe-2S] chaperone complex
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • binding 2 bridging [2Fe-2S] clsuters in a homodimeric complex
    • protein
  • protein kinase C
  • inhibiting the c Jun N terminal kinase/AP-1 and Nekappa B pathway
  • directly interacts with CSRP3 via its C-terminal half (PICOT-C) (colocalizes with CSRP3 in the Z-disc, and CSRP3 is known to play a role in anchoring calcineurin to the Z-disc in the sarcomere and is critical for calcineurin-NFAT signaling)
  • is a cleavage substrate of the apoptosis-related protein CASP3
  • interactions between GLRX3, BOLA2, and components of the cytosolic iron-sulfur cluster assembly system
  • GLRX3 interacts with embryonic ectoderm development (EED), a Polycomb Group (PcG) protein that serves as a core component of the Polycomb repressive complex 2 (PRC2) and contributes to the regulation of chromatin remodeling and cell differentiation
  • BOLA2 physically interacts with GLRX3 (glutaredoxin 3) to form a [2Fe–2S]-bridged heterotrimeric complex
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    increased the ventricular function and cardiomyocyte contractility
    tumoral     --over  
    in various human cancers including breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularcardiomyopathy 
    may provide an efficient modality for treatment of cardiac hypertrophy and heart failure
    ANIMAL & CELL MODELS