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FLASH GENE
Symbol TXNIP contributors: mct - updated : 23-10-2016
HGNC name thioredoxin interacting protein
HGNC id 16952
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an arrestin-like N-terminal domain
  • an arrestin-like C-terminal domain
  • two C-terminal tail PPXY motifs that mediate E3 ubiquitin ligase binding and TXNIP protein stability
  • HOMOLOGY
    interspecies homolog to rattus Txnip (96.92 pc)
    homolog to murine Txnip (96.14 pc)
    Homologene
    FAMILY
  • arrestin family
  • tumor suppressor family
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • alpha arrestin functioning as a natural antagonist of thioredoxin
  • having a unique role in epidermis regulating the conversion of postmitotic cells to differentiating ones
  • antitumor gene which forms a transcriptional repressor complex
  • involved in perinecrotic hypoxia
  • modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion
  • regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor
  • required for normal glucose homeostasis in the liver
  • is a novel member of the MTOR upstream that acts as a negative regulator in response to stress signals
  • AMPK is an important regulator of TXNIP transcription via modulation of MLXIPL activity
  • has multiple functions and plays an important role in redox homeostasis, increasing the production of reactive oxygen species (ROS), and oxidative stress, resulting in cellular apoptosis
  • critical role for TXNIP in AGRP neurons in mediating diet-induced obesity through the regulation of energy expenditure and adipose tissue metabolism, independently of food intake
  • metabolic regulator, which modulates insulin sensitivity and likely plays a role in type 2 diabetes
  • major redox regulator and a Tumor Suppressor Gene (TSG) in various solid tumors and hematological malignancies
  • is a new regulator of the ECD-MDM2-TP53 loop
  • is a multifunctional protein involved in diverse cellular processes such as cell proliferation and apoptosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with SCEL in keratinocytes
  • inhibits MTOR activity by binding to and stabilizing DDIT4 protein
  • inhibits adipogenesis directly, and thioredoxin binding regulates TXNIP by enhancing TXNIP protein stability
  • insulin stimulates TXNIP degradation by a PI3 kinase-dependent mechanism, which activates the ubiquitin/proteasome pathway and likely serves to mitigate insulin resistance
  • negative regulator of creatine levels, responsible for mediating substrate feedback inhibition and a potential target for modulating creatine homeostasis
  • interacts with ECD and decreases MDM2-mediated TP53 ubiquitination, leading to TP53 stabilization and an increase in TP53 activity
  • FOXO1 up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver
  • interaction between TXNIP and VAV2
  • cell & other
    REGULATION
    induced by 1,25-dihydroxyvitamin D-3
    FOXO1, responsible for glucose-induced induction of TXNIP (glucose increased the binding of FOXO1 to the TXNIP promoter via MAPK14 pathway)(Li 2009)
    AGER (AGER induces the expression of thioredoxin interacting protein (TXNIP) in Schwann cells and the injured sciatic nerve)
    high glucose that markedly increases TXNIP expression by promoting transcription
    Other regulated by various stresses including ROS, UV, and heat shock
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in diabetes and has deleterious effects on pancreatic beta-cells and the cardiovascular system
    constitutional     --over  
    is critical to regulating energy expenditure and fuel use during the extreme hypometabolic state of torpor
    constitutional     --low  
    in IBD (inflammatory bowel disease) patients suggesting that modulation of redox signaling may be an important therapeutic target
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutic use of small molecular inhibitors to reactivate TXNIP expression for cancer treatment
    neurosensorialvisualdegenerative
    targeting TXNIP expression is a potential therapeutic target for retinal neurodegenerative disease
    diabetetype 2 
    potential target to ameliorate blinding ocular complications of diabetic retinopathy
    ANIMAL & CELL MODELS