ID:IKZF1_HUMAN DESCRIPTION: RecName: Full=DNA-binding protein Ikaros; AltName: Full=Ikaros family zinc finger protein 1; AltName: Full=Lymphoid transcription factor LyF-1; FUNCTION: Transcription regulator of hematopoietic cell differentiation. Binds gamma-satellite DNA. Binds with higher affinity to gamma satellite A. Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (terminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). SUBUNIT: Heterodimer with other IKAROS family members. Interacts with IKZF4 AND IKZF5 (By similarity). Component of the chromatin- remodeling NuRD repressor complex which includes at least HDAC1, HDAC2, RBBP4, RBBP7, IKZF1, MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4. Interacts directly with the CHD4 component of the NuRD complex. Component of the BAF (SWI/SNF) gene activator complex which includes ACTB, ARID1A, ARID1B, IKZF1, ARID1A, ARID1B, SMARCA2, SMARCA4 and at least one BAF subunit. Interacts directly with the SMARCA4 component of the BAF complex (By similarity). Interacts with SUMO1; the interaction sumoylates IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform alpha); the interaction promotes sumoylation and reduces transcription repression. Interacts, to a lesser extent, with PIAS3. Interacts with PPP1CC; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with IKZF3 (By similarity). SUBCELLULAR LOCATION: Nucleus. Note=In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events (By similarity). SUBCELLULAR LOCATION: Isoform Ik2: Nucleus. Note=In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events (By similarity). SUBCELLULAR LOCATION: Isoform Ik6: Cytoplasm (By similarity). TISSUE SPECIFICITY: Abundantly expressed in thymus, spleen and peripheral blood Leukocytes and lymph nodes. Lower expression in bone marrow and small intestine. DOMAIN: The N-terminal zinc-fingers 2 and 3 are required for DNA binding as well as for targeting IKFZ1 to pericentromeric heterochromatin (By similarity). DOMAIN: The C-terminal zinc-finger domain is required for dimerization (By similarity). PTM: Phosphorylation controls cell-cycle progression from late G(1) stage to S stage. Hyperphosphorylated during G2/M phase. Dephosphorylated state during late G(1) phase. Phosphorylation on Thr-140 is required for DNA and pericentromeric location during mitosis. CK2 is the main kinase, in vitro. GSK3 and CDK may also contribute to phosphorylation of the C-terminal serine and threonine residues. Phosphorylation on these C-terminal residues reduces the DNA-binding ability. Phosphorylation/dephosphorylation events on Ser-13 and Ser-295 regulate TDT expression during thymocyte differentiation. Dephosphorylation by protein phosphatase 1 regulates stability and pericentromeric heterochromatin location. Phosphorylated in both lymphoid and non- lymphoid tissues (By similarity). PTM: Sumoylated. Simulataneous sumoylation on the 2 sites results in a loss of both HDAC-dependent and HDAC-independent repression. Has no effect on pericentromeric heterochromatin location. Desumoylated by SENP1 (By similarity). PTM: Polyubiquitinated (By similarity). DISEASE: Note=Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL. SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein family. SIMILARITY: Contains 6 C2H2-type zinc fingers. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/IkarosID258.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13422
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0019904 protein domain specific binding GO:0044212 transcription regulatory region DNA binding GO:0046872 metal ion binding
Biological Process: GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0007049 cell cycle GO:0007275 multicellular organism development GO:0007498 mesoderm development GO:0030098 lymphocyte differentiation GO:0030218 erythrocyte differentiation GO:0045892 negative regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051291 protein heterooligomerization
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
