title: Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene.
abstract: The Drosophila kelch protein is a structural component of ring canals and is required for oocyte maturation. Here, we report the cloning and genomic structure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The approximately 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a predicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylation sites and alternative splicing; thus, as many as 12 mRNA variants and six putative protein isoforms could be produced. The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans approximately 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no inactivating mutations of KLHL3 in malignant myeloid disorders with loss of 5q.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine and The Cancer Research Center, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: F
authors.initials: F
authors.lastname: Lai
authors.forename: B J
authors.initials: BJ
authors.lastname: Orelli
authors.forename: B G
authors.initials: BG
authors.lastname: Till
authors.forename: L A
authors.initials: LA
authors.lastname: Godley
authors.forename: A A
authors.initials: AA
authors.lastname: Fernald
authors.forename: L
authors.initials: L
authors.lastname: Pamintuan
authors.forename: M M
authors.initials: MM
authors.lastname: Le Beau
mesh_terms: D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004330:Drosophila / Q000737:chemistry; D029721:Drosophila Proteins; D017353:Gene Deletion; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D016366:Open Reading Frames; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020080:Tandem Repeat Sequences; D014018:Tissue Distribution
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; C489837:KLHL3 protein, human; D008840:Microfilament Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C080353:kel protein, Drosophila