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

GO curators for mouse genes have assigned the following annotations to the gene product of Rara. (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.] This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

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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 Rara
  • participates in the following biological processes:
    • cellular response to lipopolysaccharide ^[19]
    • intracellular receptor mediated signaling pathway ^[13]
    • negative regulation of transcription from RNA polymerase II promoter ^[24]
    • negative regulation of transcription, DNA-dependent ^[22]
    • negative regulation of translational initiation ^[5]
    • regulation of transcription, DNA-dependent ^{[3, 13, 23]}
    • retinoic acid receptor signaling pathway ^[4]
  • performs the following molecular functions:
    • DNA binding ^{[4, 21]}
    • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity ^[13]
    • retinoic acid receptor activity ^[4]
    • sequence-specific DNA binding ^[10]
    • sequence-specific DNA binding transcription factor activity ^{[4, 24]}
  • is located in the following cellular components:
    • cytoplasm ^[3]
    • dendrite ^[5]
    • neuronal cell body ^[5]
    • nucleus ^{[3, 19]}
• The gene product of Rara has been shown to bind to the gene products of Klf5, Med1, Med25, Nfatc2, Nrip1, Trim24. ^{[8, 15, 16, 17, 19, 23]} Researchers have inferred, based on physical interactions, that the gene product of Rara
  • performs the following molecular functions:
    • transcription factor binding ^[17]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Rara
  • participates in the following biological processes:
    • chondroblast differentiation ^[25]
    • germ cell development ^[6]
    • negative regulation of cartilage development ^[25]
    • negative regulation of cell differentiation ^[25]
    • positive regulation of gene expression ^[19]
    • regulation of granulocyte differentiation ^[11]
    • response to retinoic acid ^[11]
    • Sertoli cell fate commitment ^[7]
    • spermatogenesis ^[18]
    • ureteric bud development ^[1]
    • ventricular cardiac muscle cell differentiation ^[12]
  • performs the following molecular functions:
    • transcription regulatory region DNA binding ^[19]
• Researchers have inferred, based on genetic interactions, that the gene product of Rara
  • participates in the following biological processes:
    • growth plate cartilage development based on interactions with Rarg ^[26]
    • multicellular organism growth based on interactions with Rarg ^[26]
    • negative regulation of gene expression based on interactions with Trim24 ^[14]
    • negative regulation of transcription from RNA polymerase II promoter based on interactions with Ncor1 ^[9]
    • positive regulation of cell proliferation based on interactions with Trim24 ^[14]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Arnt, Hif1a, Rxra, Rxrb, Rxrg ^{[2, 20]}
  • performs the following molecular functions:
    • sequence-specific DNA binding based on interactions with Rxra, Rxrb, Rxrg ^[2]

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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 Rara:
  • participates in the following biological processes:
    • apoptotic cell clearance
    • cellular response to estrogen stimulus
    • cellular response to retinoic acid
    • intracellular estrogen receptor signaling pathway
    • male gonad development
    • negative regulation of cell proliferation
    • negative regulation of granulocyte differentiation
    • negative regulation of interferon-gamma production
    • negative regulation of transcription, DNA-dependent
    • negative regulation of translation
    • negative regulation of tumor necrosis factor production
    • positive regulation of binding
    • positive regulation of cell cycle
    • positive regulation of cell proliferation
    • positive regulation of interleukin-13 production
    • positive regulation of interleukin-4 production
    • positive regulation of interleukin-5 production
    • positive regulation of neuron differentiation
    • positive regulation of T-helper 2 cell differentiation
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription, DNA-dependent
    • protein phosphorylation
    • regulation of apoptotic process
    • regulation of myelination
    • regulation of synaptic plasticity
    • response to estradiol stimulus
    • response to ethanol
    • response to retinoic acid
    • retinoic acid receptor signaling pathway
    • signal transduction
  • performs the following molecular functions:
    • chromatin DNA binding
    • drug binding
    • enzyme binding
    • mRNA 5'-UTR binding
    • protein domain specific binding
    • protein heterodimerization activity
    • protein kinase A binding
    • protein kinase B binding
    • receptor binding
    • retinoic acid binding
    • retinoic acid receptor activity
    • retinoic acid-responsive element binding
    • sequence-specific DNA binding transcription factor activity
    • transcription coactivator activity
    • transcription corepressor activity
    • transcription factor binding
    • translation repressor activity, nucleic acid binding
  • is located in the following cellular components:
    • cytoplasm
    • dendrite
    • neuron projection
    • nuclear chromatin
    • nucleus
    • perinuclear region of cytoplasm

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Summary text based on GO annotations supported by structural data

• Rara encodes a protein or proteins that contain the following InterPro domains: Nuclear hormone receptor, ligand-binding, Nuclear hormone receptor, ligand-binding, core, Retinoic acid receptor, Steroid hormone receptor, Zinc finger, NHR/GATA-type, Zinc finger, nuclear hormone receptor-type, indicating that the gene product:
  • participates in the following biological processes:
    • steroid hormone mediated signaling pathway
  • performs the following molecular functions:
    • steroid hormone receptor activity
    • zinc ion binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Rara indicates that it:
  • participates in the following biological processes:
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • metal ion binding

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References

1. Batourina E et al. (2002) Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat Genet, 32:109-15. (PubMed:12195422)
2. Ben-Shushan E et al. (1995) A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. Mol Cell Biol, 15:1034-48. (PubMed:7823919)
3. Braun KW et al. (2002) Positive regulation of retinoic Acid receptor alpha by protein kinase C and mitogen-activated protein kinase in sertoli cells. Biol Reprod, 67:29-37. (PubMed:12079996)
4. Chen CF et al. (2005) Dominant-negative retinoic acid receptors elicit epidermal defects through a non-canonical pathway. J Biol Chem, 280:3012-21. (PubMed:15528198)
5. Chen N et al. (2008) The nuclear transcription factor RARalpha associates with neuronal RNA granules and suppresses translation. J Biol Chem, 283:20841-7. (PubMed:18495661)
6. Chung SS et al. (2005) Male sterility in mice lacking retinoic acid receptor alpha involves specific abnormalities in spermiogenesis. Differentiation, 73:188-98. (PubMed:15901285)
7. Doyle TJ et al. (2007) Potential functions of retinoic acid receptor A in Sertoli cells and germ cells during spermatogenesis. Ann N Y Acad Sci, 1120:114-30. (PubMed:17905941)
8. Flajollet S et al. (2006) Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation. J Biol Chem, 281:20338-48. (PubMed:16723356)
9. Horlein AJ et al. (1995) Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor [see comments] Nature, 377:397-404. (PubMed:7566114)
10. Jepsen K et al. (2007) SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron. Nature, 450:415-9. (PubMed:17928865)
11. Kastner P et al. (2001) Positive and negative regulation of granulopoiesis by endogenous RARalpha. Blood, 97:1314-20. (PubMed:11222375)
12. Kastner P et al. (1997) Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytes. Development, 124:4749-58. (PubMed:9428411)
13. Khetchoumian K et al. (2004) TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids. J Biol Chem, 279:48329-41. (PubMed:15322135)
14. Khetchoumian K et al. (2007) Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha. Nat Genet, 39:1500-6. (PubMed:18026104)
15. Le Douarin B et al. (1996) A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J, 15:6701-15. (PubMed:8978696)
16. Lee CH et al. (1999) Characterization of receptor-interacting protein 140 in retinoid receptor activities. J Biol Chem, 274:31320-6. (PubMed:10531331)
17. Lee HK et al. (2007) MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. EMBO J, 26:3545-57. (PubMed:17641689)
18. Lufkin T et al. (1993) High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci U S A, 90:7225-9. (PubMed:8394014)
19. Maitra U et al. (2009) An innate immunity signaling process suppresses macrophage ABCA1 expression through IRAK-1-mediated downregulation of retinoic acid receptor alpha and NFATc2. Mol Cell Biol, 29:5989-97. (PubMed:19752193)
20. Makita T et al. (2005) Retinoic acid, hypoxia, and GATA factors cooperatively control the onset of fetal liver erythropoietin expression and erythropoietic differentiation. Dev Biol, 280:59-72. (PubMed:15766748)
21. Perissi V et al. (2004) A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell, 116:511-26. (PubMed:14980219)
22. Potter GB et al. (2001) The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes Dev, 15:2687-701. (PubMed:11641275)
23. Shindo T et al. (2002) Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling. Nat Med, 8:856-63. (PubMed:12101409)
24. Sylvester I et al. (1994) Regulation of the Oct-4 gene by nuclear receptors. Nucleic Acids Res, 22:901-11. (PubMed:8152920)
25. Weston AD et al. (2000) Regulation of skeletal progenitor differentiation by the BMP and retinoid signaling pathways. J Cell Biol, 148:679-90. (PubMed:10684250)
26. Williams JA et al. (2009) Retinoic acid receptors are required for skeletal growth, matrix homeostasis and growth plate function in postnatal mouse. Dev Biol, 328:315-27. (PubMed:19389355)

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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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