Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MLXIPL contributors: mct/pgu - updated : 22-10-2016
HGNC name MLX interacting protein-like
HGNC id 12744
DNA
TYPE functioning gene
STRUCTURE 54.75 kb     17 Exon(s)
MAPPING cloned Y linked N status provisional
Map cen - GUSB - ASL ASL - GTF2IP1 - NCF1P - GTF2IRD2P - POM121 - NSUN5 - TRIM50A - FKBP6 - D7S489 - FZD9 - BAZ1B - BCL7B - TBL2 - D7S2476 /MLXIPL - WBSCR18 - WBSCR22 - VPS37D - STX1A - ABHD11 - CLDN3 - CLDN4 - WBSCR27 - WBSCR28 - ELN -LIMK1 - WBSCR1 - LAT2 - RFC2 - CLIP2 - GTF2IRD1 - D7S1870 - GTF2I - NCF1 - GTF2IRD2 - NCF1P - GTF2IP1 - POM121 - HIP1 - MDH2 - qter
regionally located in a region commonly deleted in Williams-Beuren syndrome
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 splicing 3288 93.1 852 - 2006 16644671
also called WBSCR14 alpha
17 splicing 3231 91 833 expression in human adipose tissue predicts insulin sensitivity, indicating that it may be an effective target for treating diabetes 2006 16644671
  • also called WBSCR14 beta, CHREBP beta
  • same ORF than alpha
  • may be a novel strategy for preventing and treating obesity-related metabolic dysfunction and type 2 diabetes
  • 17 splicing 3225 90.8 831 - 2006 16644671
  • also called WBSCR14 delta
  • same ORF than alpha
  • 17 splicing 3282 92.8 850 - 2006 16644671
  • also called WBSCR14 gamma
  • same ORF than alpha
  • 16 splicing 3094 62.8 575 - 2006 16644671
    also called WBSCR14 epsilon
    - splicing - - - - 2006 16644671
    also called WBSCR14 zeta
    - splicing - - - - 2006 16644671
    also called also called WBSCR14 eta
    - splicing - - - - 2006 16644671
    also called WBSCR14 theta
    - splicing - - - - 2006 16644671
    also called WBSCR14 iota
    - splicing - - - - 2006 16644671
    also called WBSCR14 kappa
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine   highly
     stomach   highly
    Endocrinepancreas     Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposewhite highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • bipartite nuclear localization signal (NLS)
  • a glucose-sensing module (GSM) that mediates glucose responsiveness
  • a low-glucose inhibitory domain (LID)
  • a glucose-response activation conserved element (GRACE)
  • two NES sequences, NES2 and now the new NES1 coordinate to interact together with CRM1 (exportin) for nuclear export of the carbohydrate response element binding protein )
  • a DNA binding helix-loop-helix/leucine zipper (bHLH/ZIP) domain at the C terminal region (AAs 600860), and proline-rich regions
  • C-terminal 227 AA region containing the DNA-binding domain interacted with FLII
  • mono polymer heteromer , dimer
    isoforms Precursor O-linked glycosylation of ChREBP itself or other proteins that regulate MLXIPL is essential for the production of functional MLXIPL
    HOMOLOGY
    Homologene
    FAMILY
  • Myc/Max/Mad superfamily
  • Mondo family
  • basic helix-loop-helix family of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • shuttles between the cytoplasm and nucleus
  • translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity
  • sequestered in the cytosol at low glucose concentrations, but upon stimulation with glucose and activation of Ca(2)(+) influx, rapidly translocates to the nucleus
  • ketone bodies play an important role in the regulation of MLXIPL activity by restricting MLXIPL localization to the cytoplasm, thus inhibiting fat synthesis during periods of ketosis
  • MLXIPL and FLII localized in both the cytoplasm and nucleus of cancer cells
  • basic FUNCTION
  • helix-loop-helix/leucine zipper (bHLH/ZIP) transcription factor that binds to carbohydrate response element in the promoter of some glucose-regulated genes and activates their expression upon glucose stimulation
  • regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein
  • coordinates transcriptional regulation of enzymes that channel glycolytic end-products into lipogenesis and energy storage
  • transcription factor that mediates glucose-responsive changes in gene expression in hepatocytes
  • in the liver, is responsible for converting excess carbohydrate to fatty acids for long-term storage
  • plays a key role both in redirecting glucose metabolism to anabolic pathways and suppressing TP53 activity
  • activates a number of glycolytic and lipogenic genes in response to glucose stimulation
  • responsible for conversion of dietary carbohydrate to storage fat in liver by coordinating expression of the enzymes that channel glycolytic pyruvate into lipogenesis
  • transcription factor whose expression and activity are increased in pancreatic beta-cells maintained at elevated glucose concentrations (
  • glucose-responsive transcription factor required for fatty acid synthesis in the fed state
  • important transcription factor in the pathogenesis of obesity and diabetes and their complications (
  • identified as a transcription factor regulating the induction of liver pyruvate kinase and other lipogenic genes in response to a high carbohydrate diet and it contribute potentially to the glucose-responsiveness of PNPLA3
  • functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat
  • required for maximal induction of RGS16 during fasting, suggesting that RGS16 couples hepatic glucose production with the rate of fatty acid oxidation
  • function in managing the utilization of fatty acids during prolonged fasting, by inducing expression of FGF21 to promote fat mobilization from WAT stores and RGS16 to couple gluconeogenesis to the modulation of fatty acid oxidation in hepatocytes
  • emerging as an important mediator of glucotoxity both in the liver and in the pancreatic beta-cells
  • major determinant of adipose tissue fatty acid synthesis and systemic insulin sensitivity
  • adipose tissue MLXIPL has a key role in integrating adipocyte and whole-body metabolic function and this may be mediated by transcriptional regulation of the potent CHREBP-beta isoform
  • glucose-responsive transcription factor that plays a critical role in converting excess carbohydrate to storage fat in liver
  • FLII is a component of the MLXIPL transcriptional complex and negatively regulates MLXIPL function in cancer cells
  • SREBF1 and MLXIPL are major transcriptional regulators that induce key lipogenic enzymes to promote lipogenesis in the liver
  • plays a key role in the dietary fructose transport as well as conversion into lactate and glucose through direct transcriptional control of genes involved in fructose transport, fructolysis, and gluconeogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • heterodimer with BHLHZIP protein
  • dimerizing with TCLF4
  • interacting with YWHAB, YWHAG, YWHAZ, YWHAQ for regulation of its transcriptional activity
  • inhibits the expression of several other key beta-cell genes, namely PDX1, MAFA, GCK and insulin (
  • interacting with MGEA5 (MGEA5 modification is necessary for the glucose response of MLXIPL)
  • interacting with RGS16 (inhibits hepatic fatty acid oxidation in a MLXIPL-dependent manner)
  • AMPK is an important regulator of TXNIP transcription via modulation of MLXIPL activity
  • in the excitable pancreatic beta-cell, interacts with sorcin
  • SLC2A4 regulates the expression of carbohydrate-responsive-element-binding protein, MLXIPL, a transcriptional regulator of lipogenic and glycolytic genes
  • CCND1 inhibited the activity of MLXIPL by regulating the glucose-sensing motif of this transcription factor
  • hepatic MLXIPL activity is regulated in large part by nucleocytoplasmic shuttling of MLXIPL protein via interactions with 14-3-3 proteins
  • FOXO1 inhibits beta cell TXNIP transcription, suggesting that FOXO1 confers this inhibition by interfering with MLXIPL DNA binding at target gene promoters
  • feedback loop between MXIPL and PPARA plays an important role in the regulation of lipogenesis in brown adipocytes
  • PPARGC1B-mediated coactivation of MLXIPL is likely involved in the lipogenic response to hyperglycemia
  • interacts with AR and regulates its transcriptional activity
  • direct interaction of MLXIPL with the SLC2A5 promoter, but not the SLC9A3 promoter, in the small intestine
  • cell & other
    REGULATION
    activated by high glucose
    G6P (G-6-P mediates the activation of MLXIPL)
    induced by G6P and X5P that can activate MLXIPL transactivity, but their potencies to induce MLXIPL transactivity were much lower than that of glucose
    inhibited by cAMP
    Other its activity is regulated by nucleo-cytoplasmic shuttling of MLXIPL via interactions with 14-3-3 proteins and importins
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    may exacerbate beta-cell dysfunction and accelerate beta-cell failure in type 2 diabetes
    Susceptibility to reduced triglyceride level
    Variant & Polymorphism SNP
  • G771C (Gln241His) associated with plasma triglyceride levels (lower triglyceride level)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    strategies to reduce MXIPL activity might protect against beta-cell dysfunction in type 2 diabetes
    diabetemetabolic syndrom 
    may be a novel strategy for preventing and treating obesity-related metabolic dysfunction and type 2 diabetes
    ANIMAL & CELL MODELS
  • Mice deleted for both alleles of ChREBP display diminished rates of hepatic glycolysis and lipogenesis resulting in high liver glycogen content, low plasma free fatty acid levels and reduced adipose tissue mass