Disease relevance of ORF1

• ORF1 encoded a retrovirus-like major homology region and a Cys/His box motif, also present in Gag polyproteins of related retrotransposons and retroviruses [1].
• Interestingly, in contrast to other adenoviruses, in which oncogenic viral functions are entirely encoded within the E1 region, Ad9 requires an E4 region transforming protein (ORF1) for its unique mammary oncogenicity [2].
• Adenovirus type 9 (Ad9) is distinct among human adenoviruses because it elicits solely mammary tumors in animals and its primary oncogenic determinant is the E4 region-encoded ORF1 (E4-ORF1) protein [3].
• P40 is the protein encoded by the first open reading frame (ORF1) of the human LINE-1 (L1Hs) retrotransposon; it is 338 amino acids long, has a leucine zipper motif and has been found in human teratocarcinoma cell lines and some tumor cells [4].
• VP10, a minor structural protein of the calicivirus rabbit hemorrhagic disease virus, is encoded in the small 3'-terminal open reading frame (ORF) 2 and is translated with an efficiency of approximately 20% of the preceding ORF1 [5].

High impact information on ORF1

• Using a site-directed mutagenesis approach, we found that this clone recognized a transframe epitope generated by an internal +1 frameshifting in the IL-10 sequence and so derived partly from ORF1, partly from ORF2 [6].
• Based on our results, we propose a model wherein E4-ORF1 binding to Dlg1 triggers the resulting complex to translocate to the plasma membrane and, at this site, to promote Ras-mediated PI3K activation [7].
• Despite a general belief that such interactions function solely to inactivate this suspected human tumor suppressor protein, we demonstrate here that E4-ORF1 specifically requires endogenous Dlg1 to provoke oncogenic activation of phosphatidylinositol 3-kinase (PI3K) in cells [7].
• The retrotransposition requires conserved domains in both open reading frames (ORFs), including the ORF1 cysteine- histidine motifs [8].
• Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2 [3].

Chemical compound and disease context of ORF1

• In contrast, subgroup D human adenovirus type 9 (Ad9) induces estrogen-dependent mammary tumors in female rats and requires the E4 region-encoded ORF1 oncoprotein for its tumorigenicity [9].
• The predicted amino acid sequence of the 5' proximal ORF1 (nucleotides 28 to 4218) exhibited significant identity and possessed consensus sequences characteristic of the helicase, cysteine protease, and RNA-dependent RNA polymerase sequence motifs from picornaviruses, picorna-like viruses, comoviruses, caliciviruses, and sequiviruses [10].
• The DNA sequence corresponding to ORF1, termed epsilon 1, is similar to a part of the insertion element IS51 from Pseudomonas savastanoi [11].
• Analysis of the amino acid sequence deduced from the first of these open reading frames (ORF1) revealed domains which are highly conserved among D-alanine-activating enzymes (DltA) in Lactobacillus rhamnosus (formerly Lactobacillus casei) and Bacillus subtilis [12].
• ORF1, ORF5 and ORF6 proteins had significant similarities (21-38 % identity) to the nucleocapsid protein (N), glycoprotein (G) and polymerase (L) gene products, respectively, of other rhabdoviruses, especially nucleorhabdoviruses, whereas ORF2, ORF3 and ORF4 proteins had no significant similarities to other proteins in the international databases [13].

Biological context of ORF1

• A nucleotide alignment of 10 full-length SaV genome sequences was subjected to similarity plot analysis, which indicated that the most conserved site was the polymerase-capsid junction in open reading frame 1 (ORF1) [14].
• Although the predicted amino acid sequence of ORF1 is not closely related to any known proteins, it is highly basic; thus, it has long been hypothesized that ORF1 protein functions to bind LINE-1 (L1) RNA during retrotransposition [15].
• We found that novel (i.e., unrelated) regulatory regions (5'UTR) have been frequently recruited during the evolution of L1, whereas the two open-reading frames (ORF1 and ORF2) have remained relatively conserved [16].
• The RNA sequence of the 3'-terminal 84 nucleotides of ORF1 but not the encoded peptide was found to be crucial for VP10 expression [5].
• One of gene products (ORF1) catalyzed the methylation reactions of glycine and sarcosine with S-adenosylmethionine acting as the methyl donor [17].

Anatomical context of ORF1

• The results are compatible with a model for ORF1 translation initiation in which the majority of ribosomes scan from a point 5' of nt 661 but suggest that ORF2 is not translated by attached ribosomes that reinitiate after the termination of ORF1 translation [18].
• The presence of both ORF1- and ORF2-encoded proteins in vascular endothelial cells and its apparent association with certain stages of differentiation and maturation of blood vessels may have functional relevance for vasculogenesis and/or angiogenesis [19].
• The ORF1 polypeptide targets EGFP to cytosol and nucleus whereas ORF2 targets EGFP to mitochondria [20].
• Immunohistochemical analyses revealed coexpression of ORF1 and ORF2 in prespermatogonia of fetal testis, in germ cells of adult testis, and in distinct somatic cell types, such as Leydig, Sertoli, and vascular endothelial cells [19].
• While PDZ domain-containing proteins represent cellular targets for several different viral oncoproteins, including human papillomavirus E6, human T-cell leukemia virus type 1 Tax, and human adenovirus E4-ORF1, the functional consequences for such interactions have not been elucidated [21].

Associations of ORF1 with chemical compounds

• This protein, termed Tip (tyrosine kinase interacting protein), is identified as a viral protein encoded by the open reading frame 1 (ORF1) [22].
• Disruption of ORF1 with a chloramphenicol-resistance cassette (CAT) rendered the H. pylori mutants more susceptible to cupric ion than their parental strains, whereas there is no significant alteration of susceptibility to Ni2+, Cd2d+ and Hg2+ between the mutants and the parental strains [23].
• The first open reading frame (ORF1) of PsCR1 has two unusual arrangements of Cys residues [24].
• Rather, the lysine substitutions alter the delicate balance between the ORF1 protein's melting and reannealing activities, thereby reducing its nucleic acid chaperone activity [25].
• An in-frame fusion of ORF1 to the malE gene of the expression vector, pMAL-c2, yielded a protein that was immunostained with antibodies raised against the maltose binding protein and A. naeslundii T14V whole bacteria [26].

Other interactions of ORF1

• Galectin-3 mRNA and L1-related ORF1/ p40 protein showed similar expression patterns [27].
• The induction of p38delta appears to be mediated by an ORF1/p40-dependent process [28].
• The fact that several different human virus oncoproteins, including adenovirus type 9 E4-ORF1, evolved to target the Dlg1 mammalian homolog of the membrane-associated Drosophila discs-large tumor suppressor has implicated this cellular factor in human cancer [7].
• Two ORFs were predicted within human MGC9753 mRNA, and ORF1 (nucleotide position 18-980 of NM_033419.1) was predicted as the coding region of human MGC9753 mRNA based on comparative genomics [29].
• A database search revealed that 2P1 was 91% identical to ORF1 of E3-3, a rat gene probably involved in the regulation of alternative splicing [30].

Analytical, diagnostic and therapeutic context of ORF1

• Real-time quantitative RT-PCR was used for detecting ORF1 messenger RNA (mRNA) [27].
• Based on UV crosslinking and electrophoretic mobility-shift assays using purified components, we demonstrate here that the ORF1 protein encoded by mouse L1 binds nucleic acids with a strong preference for RNA and other single-stranded nucleic acids [15].
• To assess genetic heterogeneity of the TTV genome in more detail, a sequence analysis of PCR fragments (271 bp) amplified from open reading frame 1 (ORF1) was performed [31].
• Western blot analysis indicated that MAEBL expression was better correlated with the appearance of the canonical ORF1 transcript [32].
• Confocal microscopy imaging of cells transfected with a vector plasmid that provided expression of the entire Norwalk virus N-terminal protein (amino acids 1 to 398 of the ORF1 polyprotein) showed colocalization of this protein with cellular proteins of the Golgi apparatus [33].

References