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FLASH GENE
Symbol ISL1 contributors: shn/npt - updated : 31-05-2015
HGNC name ISL LIM homeobox 1
HGNC id 6132
Location 5q11.1      Physical location : 50.678.957 - 50.690.557
Synonym name
  • ISL1 transcription factor, LIM/homeodomain, (islet-1)
  • islet-1 nuclear protein
  • Synonym symbol(s) ISL-1, ISLET1
    DNA
    TYPE functioning gene
    STRUCTURE 11.61 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map ISL1 gene has been mapped by linkage analysis on 5q
    regionally located cen - D5S466 - D5S822 - ISL1 - D5S660 - D5S2035 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2729 36.7 349 mouse tooth and mandibular development Mitsiadis et al, 2003
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal glandmedulla   
    Nervousbraindiencephalonepithalamuspineal gland 
     brainbasal nucleistriatum   Homo sapiensFetal
     gangliasensory gangliadorsal root  
    Reproductivemale systemtestis   
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsensoryvisualinner nuclear layer 
    Nervousautonomous   
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text In embryonic mice, sensory neurons coexpress the pan-sensory homeodomain ranscription factors Islet1 and Brn3a
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two cysteine-rich (LIM) domain
  • an helix-turn-helix DNA binding domain
  • HOMOLOGY
    interspecies ortholog to murine, Isl1
    ortholog to isl1, Xenopus (Silurana) tropicalis
    ortholog to isl-1, Rattus norvegicus
    ortholog to islet1, Danio rerio
    intraspecies homolog to Isl2, Lim1 and Lim2, Lhx6 and Lhx7
    Homologene
    FAMILY
  • LIM-homeo domain family of transcription factors
  • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • plays an important role in the embryogenesis of pancreatic islets of Langerhans
  • required for proliferation, survival, and migration of recently defined second heart field progenitors
  • LIM homeodomain protein that plays an important role in insulin gene transcriptional activation and islet cell formation and may be required for motor neuron generation
  • In the spinal cord, Islet1 has an essential role in the early survival of motor neurons
  • Islet1 is required to terminate the expression of key
  • regulators of the neurogenic phase of sensory development
  • requirement in the development of restricted telencephalic cholinergic neurons and the development of cholinergic neurons in anatomically disparate sites is linked to ISL1 function (Elshatory 2008)
  • ISL1 and POU4F2 concurrently bind to and synergistically regulate the expression of a common set of retinal ganglion cells-specific genes
  • essential for pancreatic islet cell and dorsal mesenchyme development
  • transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages
  • plays essential roles during embryogenesis
  • required for the survival and specification of spinal cord motor neurons, and required for survival of cranial ganglia neurons
  • required for the nuclear accumulation of CTNNB and hence for activation of the CTNNB pathway, and the CTNNB pathway maintains ISL1 expression
  • hindlimb-specific transcriptional regulator of initiation
  • transcription factor that has been associated with the multipotency of human cardiac progenitors
  • is required for the normal expression of Ikaros in striatal neuron progenitors
  • ISL1-expressing progenitors give rise to striatal neurons belonging to the striatonigral pathway
  • is required for the normal development of striatonigral neurons
  • marks the progenitors of the striatonigral pathway and is required for their development and survival
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • LIM complex composed of ISL1 and LHX3 directs the specification of spinal motor neurons (MNs) in embryos
  • ISL1-GATA3 transcription regulatory axis is essential for normal pyloric development
  • crucial regulatory axis for the ventral axonal trajectory of developing spinal MNs, consisting of the ISL1-LHX3 complex, STAM1 and CXCR4
  • INTERACTION
    DNA binding to the enhancer region of the insulin gene
    RNA
    small molecule
    protein
  • interacting with NEUROD1 (could activate insulin gene transcription synergistically)
  • transcriptional activator for insulin gene expression, and the interactions of ISL1 with NEUROD1 are required for the transcriptional activity of the insulin gene
  • FBXO25 acts as an ubiquitin E3 ligase to target cardiac transcription factors including NKX2-5, ISL1, and HAND1, indicating that cardiac protein homeostasis through FBXO25 has a pivotal impact on cardiac development
  • binds to a known POU4F1-regulated enhancer in the NEUROD4 gene, suggesting a mechanism of interaction between these genes
  • novel transcriptional regulator of LHX3
  • ISL1 directly regulates FGF10 transcription during human cardiac outflow formation
  • AJUBA binds ISL1, represses its transcriptional activity, and is also required for autorepression of ISL1 expression in an Retinoic acid (RA)-dependent manner
  • LDB1 is a critical transcriptional coregulator during islet alpha-, beta-, and delta-cell development through ISL1-dependent and potentially ISL1-independent control
  • CDH6 is necessary for the generation of ISL1-positive dorsal interneurons, as well as the initiation of pre-migratory neural crest cell emigration
  • potent BARX1 functions in intestinal rotation and stomach myogenesis occur through ISL1, PITX1, SIX2 and PITX2, intermediary transcription factors
  • LDB1 binds to the key regulator of cardiac progenitors, ISL1, and protects it from degradation
  • is a transcription factor important for pancreatic islet cell development, maturation, and function, which largely requires interaction with LDB1 coregulator
  • SSBP3 interacts with LDB1 and ISL1 in beta-cell lines and in human islets and is coexpressed with LDB1 and ISL1 pancreas tissue
  • SSBP3 is a critical component of LDB1-ISL1 regulatory complexes, required for expression of critical beta-cell target genes
  • cell & other
    REGULATION
    Other regulated by CTNNB1 in cardiovascular progenitors (required for multiple aspects of cardiogenesis)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to obesity
  • to non insulin dependent diabetes mellitus, familial
  • to non-syndromic congenital heart disease
  • Variant & Polymorphism SNP , other
  • SNP47A>G increases the body weight in diabetic morbidly obese
  • genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease.
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mice with a homozygous null mutation in the Isl1 gene exhibited growth retardation and heart abnormalities (Cai et al, 2003)
  • Mouse conditional knockout for Isl1 gene showed a loss of the nociceptive markers TrkA, TrkB and Runx1 and a near absence of cutaneous innervation, an excess of cell apoptosis, a ganglion size markedly diminished, a profound loss of cutaneous innervation. Mouse Isl1 CKO exhibits rofound deficits in the sensory innervation of the CNS and periphery, extensive changes in sensory gene expression, and markedly increased sensory apoptosis, with relative sparing of proprioceptor neuron (Sun et al, 2008)