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

GO curators for mouse genes have assigned the following annotations to the gene product of Six1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [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 Six1
  • participates in the following biological processes:
    • negative regulation of transcription from RNA polymerase II promoter ^[12]
    • positive regulation of transcription from RNA polymerase II promoter ^[1]
    • regulation of transcription, DNA-dependent ^[11]
  • performs the following molecular functions:
    • sequence-specific DNA binding ^{[6, 17]}
    • sequence-specific DNA binding transcription factor activity ^[1]
  • is located in the following cellular components:
    • nucleus ^{[11, 17]}
    • transcription factor complex ^[11]
• The gene product of Six1 has been shown to bind to the gene products of Eya1, Tbx18. ^{[3, 13, 15, 19]} Researchers have inferred, based on physical interactions, that the gene product of Six1
  • performs the following molecular functions:
  • is located in the following cellular components:
    • transcription factor complex ^[19]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Six1
  • participates in the following biological processes:
    • cochlea morphogenesis ^[20]
    • epithelial cell differentiation ^[23]
    • facial nerve morphogenesis ^[20]
    • generation of neurons ^[10]
    • inner ear development ^[2]
    • kidney development ^[4]
    • mesonephric tubule formation ^[9]
    • metanephric mesenchyme development ^[9]
    • middle ear morphogenesis ^[20]
    • negative regulation of branching involved in ureteric bud morphogenesis ^[12]
    • negative regulation of neuron apoptotic process ^[10]
    • organ induction ^[18]
    • otic vesicle development ^[21]
    • pattern specification process ^[21]
    • positive regulation of branching involved in ureteric bud morphogenesis ^[9]
    • positive regulation of transcription, DNA-dependent ^[9]
    • positive regulation of ureteric bud formation ^[9]
    • regulation of branch elongation involved in ureteric bud branching ^[9]
    • regulation of neuron differentiation ^[22]
    • sensory perception of sound ^[20]
    • skeletal system morphogenesis ^[20]
    • thymus development ^[23]
    • thyroid gland development ^[23]
    • ureter smooth muscle cell differentiation ^[13]
    • ureteric bud development ^[18]
• Researchers have inferred, based on genetic interactions, that the gene product of Six1
  • participates in the following biological processes:
    • anatomical structure development based on interactions with Eya1, Six4 ^[23]
    • aorta morphogenesis based on interactions with Eya1, Fgf8, Tbx1 ^[7]
    • branching involved in ureteric bud morphogenesis based on interactions with Eya1 ^[18]
    • embryonic cranial skeleton morphogenesis based on interactions with Six4 ^[8]
    • embryonic skeletal system morphogenesis based on interactions with Six4 ^[5]
    • inner ear morphogenesis based on interactions with Six4 ^[5]
    • myoblast migration based on interactions with Six4 ^[5]
    • outflow tract morphogenesis based on interactions with Eya1, Fgf8, Tbx1 ^[7]
    • pattern specification process based on interactions with Eya1 ^[23]
    • pharyngeal system development based on interactions with Eya1, Fgf8, Tbx1 ^[7]
    • positive regulation of mesenchymal cell proliferation involved in ureter development based on interactions with Tbx18 ^[13]
    • positive regulation of secondary heart field cardioblast proliferation based on interactions with Eya1 ^[7]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Eya1 ^[7]
    • regulation of gene expression based on interactions with Six4 ^[14]
    • regulation of protein localization based on interactions with Six4 ^[14]
    • regulation of synaptic growth at neuromuscular junction based on interactions with Six4 ^[14]
    • renal system development based on interactions with Bmp4 ^[12]
    • skeletal muscle tissue development based on interactions with Six4 ^[5]
    • thymus development based on interactions with Six4 ^[23]
    • ureteric bud development based on interactions with Eya1, Pax2 ^[16]
  • performs the following molecular functions:
    • chromatin binding based on interactions with Eya3, Ski ^[19]

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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 Six1:
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter
    • protein localization to nucleus
  • performs the following molecular functions:
    • DNA binding
    • sequence-specific DNA binding
    • transcription regulatory region DNA binding
  • is located in the following cellular components:
    • nucleolus
    • nucleus

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Six1 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • transcription, DNA-dependent

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References

1. Ando Z et al. (2005) Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and Six4. FEBS J, 272:3026-41. (PubMed:15955062)
2. Bosman EA et al. (2009) Catweasel mice: a novel role for Six1 in sensory patch development and a model for branchio-oto-renal syndrome. Dev Biol, 328:285-96. (PubMed:19389353)
3. Buller C et al. (2001) Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome. Hum Mol Genet, 10:2775-81. (PubMed:11734542)
4. Bush KT et al. (2006) Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system. Dev Biol, 298:571-84. (PubMed:16934795)
5. Grifone R et al. (2005) Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo. Development, 132:2235-49. (PubMed:15788460)
6. Grifone R et al. (2007) Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo. Dev Biol, 302:602-16. (PubMed:17098221)
7. Guo C et al. (2011) A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest, 121:1585-95. (PubMed:21364285)
8. He G et al. (2010) Inactivation of Six2 in mouse identifies a novel genetic mechanism controlling development and growth of the cranial base. Dev Biol, 344:720-30. (PubMed:20515681)
9. Kobayashi H et al. (2007) Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric-tubule defects. Mech Dev, 124:290-303. (PubMed:17300925)
10. Konishi Y et al. (2006) Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis. Brain Res, 1116:93-102. (PubMed:16938278)
11. Li X et al. (2003) Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature, 426:247-54. (PubMed:14628042)
12. Nie X et al. (2011) Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis. Dev Biol, 352:141-51. (PubMed:21281623)
13. Nie X et al. (2010) SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development, 137:755-65. (PubMed:20110314)
14. Richard AF et al. (2011) Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1 and Six4 gene expression. Dev Biol, 359:303-20. (PubMed:21884692)
15. Ruf RG et al. (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A, 101:8090-5. (PubMed:15141091)
16. Sajithlal G et al. (2005) Eya 1 acts as a critical regulator for specifying the metanephric mesenchyme. Dev Biol, 284:323-36. (PubMed:16018995)
17. Spitz F et al. (1998) Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc Natl Acad Sci U S A, 95:14220-5. (PubMed:9826681)
18. Xu PX et al. (2003) Six1 is required for the early organogenesis of mammalian kidney. Development, 130:3085-94. (PubMed:12783782)
19. Zhang H et al. (2009) Ski regulates muscle terminal differentiation by transcriptional activation of Myog in a complex with Six1 and Eya3. J Biol Chem, 284:2867-79. (PubMed:19008232)
20. Zheng W et al. (2003) The role of Six1 in mammalian auditory system development. Development, 130:3989-4000. (PubMed:12874121)
21. Zou D et al. (2006) Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear. Dev Biol, 298:430-41. (PubMed:16916509)
22. Zou D et al. (2004) Eya1 and Six1 are essential for early steps of sensory neurogenesis in mammalian cranial placodes. Development, 131:5561-72. (PubMed:15496442)
23. Zou D et al. (2006) Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev Biol, 293:499-512. (PubMed:16530750)

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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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