Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Isl1. (This text reflects annotations as of Tuesday, May 21, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations in this gene have been associated with maturity-onset diabetes of the young. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Isl1
  • participates in the following biological processes:
    • positive regulation of cell proliferation ^[7]
    • positive regulation of DNA binding ^[7]
    • positive regulation of granulocyte colony-stimulating factor production ^[4]
    • positive regulation of granulocyte macrophage colony-stimulating factor production ^[4]
    • positive regulation of interferon-gamma production ^[4]
    • positive regulation of interleukin-1 alpha production ^[4]
    • positive regulation of interleukin-1 beta production ^[4]
    • positive regulation of interleukin-12 production ^[4]
    • positive regulation of interleukin-6 production ^[4]
    • positive regulation of macrophage colony-stimulating factor production ^[4]
    • positive regulation of transcription from RNA polymerase II promoter ^[10]
    • positive regulation of tumor necrosis factor production ^[4]
    • positive regulation of tyrosine phosphorylation of Stat3 protein ^[7]
    • positive regulation vascular endothelial growth factor production ^[4]
  • performs the following molecular functions:
    • chromatin binding ^{[10, 15]}
    • DNA binding ^[10]
    • RNA polymerase II transcription coactivator activity ^[7]
  • is located in the following cellular components:
    • intracellular ^{[2, 9]}
    • nucleus ^{[7, 8, 14, 15, 17, 18]}
• The gene product of Isl1 has been shown to bind to the gene products of Ldb1, Rlim, Stat3. ^{[3, 7, 17]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Isl1
  • participates in the following biological processes:
    • cardiac cell fate determination ^[10]
    • cardiac muscle cell myoblast differentiation ^[10]
    • heart development ^[5]
    • innervation ^[19]
    • mesenchymal cell differentiation ^[1]
    • negative regulation of inflammatory response ^[4]
    • negative regulation of neuron apoptotic process ^[19]
    • negative regulation of transcription from RNA polymerase II promoter ^[19]
    • neuron differentiation ^{[6, 16]}
    • neuron fate specification ^[19]
    • pancreas development ^[1]
    • peripheral nervous system neuron axonogenesis ^[19]
    • pituitary gland development ^[20]
    • positive regulation of angiogenesis ^[4]
    • positive regulation of transcription from RNA polymerase II promoter ^[19]
    • regulation of gene expression ^[17]
    • regulation of secondary heart field cardioblast proliferation ^[10]
    • retinal ganglion cell axon guidance ^[15]
    • sensory system development ^[19]
    • spinal cord motor neuron differentiation ^[16]
    • trigeminal nerve development ^[19]
• Researchers have inferred, based on genetic interactions, that the gene product of Isl1
  • participates in the following biological processes:
    • atrial septum morphogenesis based on interactions with Ctnnb1 ^[11]
    • cardiac right ventricle morphogenesis based on interactions with Ctnnb1 ^[11]
    • endocardial cushion morphogenesis based on interactions with Ctnnb1 ^[11]
    • heart morphogenesis based on interactions with Smo ^[12]
    • negative regulation of canonical Wnt receptor signaling pathway based on interactions with Ctnnb1 ^[10]
    • negative regulation of neuron differentiation based on interactions with Isl2 ^[21]
    • neural crest cell migration based on interactions with Smo ^[12]
    • neuron differentiation based on interactions with Pou4f2 ^[13]
    • neuron fate commitment based on interactions with Isl2 ^[21]
    • outflow tract morphogenesis based on interactions with Ctnnb1 ^[11]
    • outflow tract septum morphogenesis based on interactions with Ctnnb1 ^[11]
    • pharyngeal system development based on interactions with Ctnnb1 ^[11]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Pou4f2 ^[15]
    • spinal cord motor neuron cell fate specification based on interactions with Lhx3 ^[17]
    • ventricular cardiac muscle tissue morphogenesis based on interactions with Ctnnb1 ^[11]
    • visceral motor neuron differentiation based on interactions with Isl2 ^[21]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Isl1:
  • participates in the following biological processes:
    • cardiac cell fate determination
    • negative regulation of intracellular estrogen receptor signaling pathway
    • negative regulation of protein homodimerization activity
    • positive regulation of insulin secretion
    • positive regulation of transcription from RNA polymerase II promoter
    • regulation of transcription, DNA-dependent
    • secondary heart field specification
  • performs the following molecular functions:
    • bHLH transcription factor binding
    • enhancer sequence-specific DNA binding
    • estrogen receptor binding
    • ligand-dependent nuclear receptor binding
    • RNA polymerase II activating transcription factor binding
    • RNA polymerase II transcription coactivator activity
    • sequence-specific DNA binding
  • is located in the following cellular components:
    • nucleus

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Summary text based on GO annotations supported by structural data

• Isl1 encodes a protein or proteins that contain the following InterPro domains: Homeobox, conserved site, Homeodomain, Homeodomain-like, Zinc finger, LIM-type, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent
  • performs the following molecular functions:
    • sequence-specific DNA binding transcription factor activity
    • zinc ion binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Isl1 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
  • performs the following molecular functions:
    • metal ion binding

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References

1. Ahlgren U et al. (1997) Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature, 385:257-60. (PubMed:9000074)
2. Arber S et al. (1999) Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity [see comments] Neuron, 23:659-74. (PubMed:10482234)
3. Bach I et al. (1999) RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nat Genet, 22:394-9. (PubMed:10431247)
4. Barzelay A et al. (2012) Islet-1 gene delivery improves myocardial performance after experimental infarction. Atherosclerosis, 223:284-90. (PubMed:22727192)
5. Cai CL et al. (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell, 5:877-89. (PubMed:14667410)
6. Elshatory Y et al. (2008) The LIM-homeobox gene Islet-1 is required for the development of restricted forebrain cholinergic neurons. J Neurosci, 28:3291-7. (PubMed:18367596)
7. Hao A et al. (2005) The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities. Mol Biol Cell, 16:1569-83. (PubMed:15659653)
8. Hao Z et al. (1999) Differential expression of Hoxa-2 protein along the dorsal-ventral axis of the developing and adult mouse spinal cord. Dev Dyn, 216:201-17. (PubMed:10536059)
9. Jensen J et al. (2000) Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes, 49:163-76. (PubMed:10868931)
10. Kwon C et al. (2009) A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nat Cell Biol, 11:951-7. (PubMed:19620969)
11. Lin L et al. (2007) Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proc Natl Acad Sci U S A, 104:9313-8. (PubMed:17519333)
12. Lin L et al. (2006) Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Dev Biol, 295:756-63. (PubMed:16687132)
13. Mak KK et al. (2008) Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development, 135:1947-56. (PubMed:18434416)
14. Mitsiadis TA et al. (2003) Role of Islet1 in the patterning of murine dentition. Development, 130:4451-4460. (PubMed:12900460)
15. Pan L et al. (2008) ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells. Development, 135:1981-90. (PubMed:18434421)
16. Pfaff SL et al. (1996) Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell, 84:309-20. (PubMed:8565076)
17. Song MR et al. (2009) Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity. Development, 136:2923-32. (PubMed:19666821)
18. Sumazaki R et al. (2004) Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet, 36:83-7. (PubMed:14702043)
19. Sun Y et al. (2008) A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci, 11:1283-93. (PubMed:18849985)
20. Takuma N et al. (1998) Formation of Rathke's pouch requires dual induction from the diencephalon. Development, 125:4835-40. (PubMed:9806931)
21. Thaler JP et al. (2004) A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Neuron, 41:337-50. (PubMed:14766174)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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