InterPro domain: IPR043640

The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression [ 1 ].

In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) [ 2 , 2 ].

Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila [ 3 ].

This entry represents the C-terminal domain homology domain fthat is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. This domain consists of eight helices and is distantly related to tetratrico peptide repeat motifs. The CHD domain mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. [ 4 ].

1. Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability. Hum. Mol. Genet. 20, 1873-85
2. Lilliputian: an AF4/FMR2-related protein that controls cell identity and cell growth. Development 128, 791-800
3. Transcriptional regulation of cytoskeletal functions and segmentation by a novel maternal pair-rule gene, lilliputian. Development 128, 801-13
4. Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization. J. Biol. Chem. 294, 10663-10673