KLF1
Domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Function
Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis. Is a dual regulator of fetal-to-adult globin switching. Binds to the CACCC box in the beta-globin gene promoter and acts as a preferential activator of this gene. Furthermore, it binds to the BCL11A promoter and activates expression of BCL11A, which in turn represses the HBG1 and HBG2 genes. This dual activity ensures that, in most adults, fetal hemoglobin levels are low. Able to activate CD44 and AQP1 promoters. When sumoylated, acts as a transcriptional repressor by promoting interaction with CDH2/MI2beta and also represses megakaryocytic differentiation.
Involvement in disease
Anemia, congenital dyserythropoietic, 4
CDAN4
A blood disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDA4 also have increased levels of fetal hemoglobin.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Acetylated; can be acetylated on both Lys-274 and Lys-288. Acetylation on Lys-274 (by CBP) appears to be the major site affecting EKLF transactivation activity (By similarity).
Sumoylated; sumoylation, promoted by PIAS1, leads to repression of megakaryocyte differentiation. Also promotes the interaction with the CDH4 subunit of the NuRD repression complex (By similarity).
Phosphorylated primarily on serine residues in the transactivation domain. Phosphorylation on Thr-23 is critical for the transactivation activity (By similarity).
Sequence Similarities
Belongs to the krueppel C2H2-type zinc-finger protein family.
Tissue Specificity
Expression restricted to adult bone marrow and fetal liver. Not expressed in myeloid nor lymphoid cell lines.
Cellular localization
- Nucleus
- Colocalizes with SUMO1 in nuclear speckles.
Alternative names
EKLF, KLF1, Krueppel-like factor 1, Erythroid krueppel-like transcription factor