title: Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukaemia.
abstract: The AF-4 gene on human chromosome 4q21 is involved in reciprocal translocations to the ALL-1 gene on chromosome 11q23, which are associated with acute lymphoblastic leukaemias. A set of recombinant phage carrying genomic fragments for the coding region and flanking sequences of the AF-4 gene were isolated. Phage inserts were assembled into four contigs with 21 exons, and an intron phase map was produced enabling the interpretation of translocation-generated fusion proteins. The gene contains two alternative first exons, 1a and 1b, both including a translation initiation codon. The translocation breakpoint cluster region is flanked by exons 3 and 6 and two different polyadenylation signals were identified. Polyclonal antisera directed against three different portions of the AF-4 protein were produced and used to detect a 116 kD protein in cellular extracts of human B-lymphoblastoid and proB cell lines. In mitogen-stimulated human peripheral blood mononuclear cells the AF-4 antigen was predominantly located in the nucleus. The AF-4 gene is a member of the AF-4, LAF-4 and FMR-2 gene family. The members of this family encode serine-proline-rich proteins with properties of nuclear transcription factors. Comparison of AF-4 protein coding sequences with the LAF-4 and FMR-2 sequences revealed five highly conserved domains of potential functional relevance.
authors.affiliation: Department of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Nilson
authors.forename: M
authors.initials: M
authors.lastname: Reichel
authors.forename: M G
authors.initials: MG
authors.lastname: Ennas
authors.forename: R
authors.initials: R
authors.lastname: Greim
authors.forename: C
authors.initials: C
authors.lastname: Knörr
authors.forename: G
authors.initials: G
authors.lastname: Siegler
authors.forename: J
authors.initials: J
authors.lastname: Greil
authors.forename: G H
authors.initials: GH
authors.lastname: Fey
authors.forename: R
authors.initials: R
authors.lastname: Marschalek
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017421:Sequence Analysis; D015534:Trans-Activators; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic
chemical_list: C099930:AFF2 protein, human; C097738:AFF3 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D035602:Transcriptional Elongation Factors; C081449:AFF1 protein, human