title: The novel human HUEL (C4orf1) protein shares homology with the DNA-binding domain of the XPA DNA repair protein and displays nuclear translocation in a cell cycle-dependent manner.
abstract: We have previously isolated and characterized a novel human gene HUEL (C4orf1) that is ubiquitously expressed in a wide range of human fetal, adult tissues and cancer cell lines. HUEL maps to region 4p12-p13 within the short arm of chromosome 4 whose deletion is frequently associated with bladder and other carcinomas. Here we present the genomic organization, sizes and boundaries of exons and introns of HUEL. The GC-rich upstream genomic region and 5' untranslated region (UTR) together constitute a CpG island, a hallmark of housekeeping genes. The 3250 bp HUEL cDNA incorporates a 1704 bp ORF that translates into a hydrophilic protein of 568-amino acids (aa), detected as a band of approximately 70 kDa by Western blotting. We have isolated the murine homolog of HUEL which exhibits 89% nucleotide and 94% amino acid identity to its human counterpart. The HUEL protein shares significant homology with the minimal DNA-binding domain (DNA-BD) of the DNA repair protein encoded by the xeroderma pigmentosum group A (XPA) gene. Other notable features within HUEL include the putative nuclear receptor interaction motif, nuclear localization and export signals, zinc finger, leucine zipper and acidic domains. Mimosine-mediated cell cycle synchronization of PLC/PRF/5 liver cancer cells clearly portrayed translocation of HUEL into the nucleus specifically during the S phase of the cell cycle. Yeast two-hybrid experiments revealed interactions of HUEL with two partner proteins (designated HIPC and HIPB) bearing similarity to a mitotically phosphorylated protein and to reverse transcriptase. Co-immunoprecipitation assays validated the interaction between HUEL and HIPC proteins in mammalian cells. HUEL is likely to be an evolutionarily conserved, housekeeping gene that plays a role intimately linked with cellular replication, DNA synthesis and/or transcriptional regulation.
authors.affiliation: Human Genome Laboratory, Department of Microbiology, Faculty of Medicine, National University of Singapore, Kent Ridge 117597, Singapore.
authors.forename: Del L C
authors.initials: DL
authors.lastname: Sim
authors.forename: W M
authors.initials: WM
authors.lastname: Yeo
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D001749:Urinary Bladder Neoplasms; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D027682:Cation Transport Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C120900:SLC30A9 protein, human; D014157:Transcription Factors; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse