Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse
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Established Ikaros as a family of lymphocyte-restricted zinc finger DNA binding proteins in human and mouse, with multiple alternatively spliced isoforms
"differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues. Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes."
Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of mouse Ikaros/LyF-1
Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes
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Identified Ikaros as a component of the NuRD chromatin remodeling complex and showed direct interaction with CHD4 and SMARCA4, demonstrating Ikaros targets both NuRD and BAF complexes in lymphocytes
"a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin."
Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities
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Characterized IKZF4 (Eos) and IKZF5 (Pegasus) interactions with IKZF1 (Ikaros), demonstrating heterodimerization between Ikaros family members
"Pegasus self-associates and binds to other family members but recognizes distinct DNA-binding sites. Eos and Pegasus repress the expression of reporter genes containing their recognition elements. Our results suggest that these proteins may associate with previously described Ikaros family proteins in lymphoid cells"
Structural studies on a protein-binding zinc-finger domain of Eos reveal both similarities and differences to classical zinc fingers.
Human Ikaros function in activated T cells is regulated by coordinated expression of its largest isoforms
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Demonstrated that Ikaros function in human T cells depends on coordinated expression of different isoforms, with dominant-negative isoforms modulating activity; confirmed subcellular localization and gamma-satellite DNA binding
"the DNA binding affinity of hIK-H differs from that of hIK-VI. Co-expression of hIk-H with hIk-VI alters the ability of Ikaros complexes to bind DNA motifs found in pericentromeric heterochromatin (PC-HC). In the nucleus, hIK-VI is localized solely in PC-HC, whereas the hIK-H protein exhibits dual centromeric and non-centromeric localization."
The role of Ikaros in human erythroid differentiation
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Demonstrated that Ikaros plays a role in human erythroid differentiation and lymphocyte differentiation, using isoform manipulation of hematopoietic progenitors
"Ikaros is involved in human adult or fetal erythroid differentiation as well as in the commitment between erythroid and myeloid cells"
Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing
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Demonstrated Ikaros binding to gamma-satellite DNA at pericentromeric heterochromatin
"These arrays contain CTCF and Ikaros binding sites. In MEL cells, this gamma-satellite DNA activity depends on binding of Ikaros proteins involved in differentiation along the hematopoietic pathway."
Next-generation sequencing to generate interactome datasets
Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene
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Identified IKZF1 Y210C mutation causing CVID13, characterized DNA binding defect and loss of pericentromeric heterochromatin localization in the mutant
"DNA studies revealed a point mutation in one allele of the IKAROS gene, resulting in an amino acid substitution in the DNA-binding zinc finger domain. Functional studies demonstrated that the observed mutation decreased Ikaros DNA-binding affinity, and immunofluorescence microscopy revealed aberrant Ikaros pericentromeric localization."
Cell cycle-specific function of Ikaros in human leukemia
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Demonstrated cell cycle-dependent DNA binding and nuclear localization of Ikaros, with phosphorylation regulating these properties
"RESULTS: The DNA-binding activity of human Ikaros complexes undergoes dynamic changes as the cell cycle progresses"
Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros
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SYK phosphorylates Ikaros at S361 and S364, augmenting nuclear localization and sequence-specific DNA binding activity. SYK-induced Ikaros activation is essential for nuclear localization and optimal transcription factor function.
"SYK phoshorylates Ikaros at unique C-terminal serine phosphorylation sites S358 and S361, thereby augmenting its nuclear localization and sequence-specific DNA binding activity"
A proteome-scale map of the human interactome network
Loss of B Cells in Patients with Heterozygous Mutations in IKAROS
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Identified multiple IKZF1 mutations (R162Q, R162L, H167R, R184Q) in CVID13 patients that abolish DNA binding, demonstrating essential role of zinc finger domain integrity for Ikaros function
"Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers"
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
Systematic identification of post-transcriptional regulatory modules
Multimodal cell maps as a foundation for structural and functional genomics