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Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). 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 (fikzfterminal 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). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067).
Abundantly expressed in thymus, spleen and peripheral blood Leukocytes and lymph nodes. Lower expression in bone marrow and small intestine.
Involvement in disease
Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL. Chromosomal aberrations involving IKZF1 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), with BCL6.
Belongs to the Ikaros C2H2-type zinc-finger protein family. Contains 6 C2H2-type zinc fingers.
The N-terminal zinc-fingers 2 and 3 are required for DNA binding as well as for targeting IKFZ1 to pericentromeric heterochromatin. The C-terminal zinc-finger domain is required for dimerization.
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). Phosphorylation at Ser-361 and Ser-364 downstream of SYK induces nuclear translocation. 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. Polyubiquitinated.
Cytoplasm; Nucleus. 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 and Nucleus. 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).