F box gene transcriptions

Associate Editor(s)-in-Chief: Henry A. Hoff

"The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction."

Gene transcriptions

"The F-box of Elongin A binds Elongin C (El C). The association of Elongins B and C with A increases Elongin A transcriptional activity."

Def. that "part of a biomolecule (such as a protein) that is the target of an immune response" is called an epitope.

"SCF complexes generally recognize substrates after they are phosphorylated on specific epitopes [10]. Phosphorylation is one of the major mechanisms used by cells to rapidly transduce signals. SCF complexes are therefore ideal for dynamic processes that require an abrupt change to be made irreversible (at least in the short term) via the degradation of key proteins. Examples of such processes are cell-cycle phase transitions - during which the cell-cycle regulators that were required for the previous phase are degraded as the cell enters the new phase - and shifts in transcription that last for a longer time period than otherwise because a transcriptional inhibitor is degraded. There is a wide variety of SCF targets that include cell-cycle regulators, for example, G1-phase cyclins, cyclin-dependent kinase inhibitors, DNA replication factors, and transcription factors that promote cell-cycle progression, as well as non-cell-cycle functions, such as a cytoskeletal regulator, cell-surface receptors, transcription-factor inhibitors, and non-cell-cycle transcription factors (Table 2)."

"Second, Elongin A, the transcriptionally active subunit of the Elongin (SIII) complex - which facilitates transcription elongation by RNA polymerase II [16] - is an F-box protein (Figure 2c). Elongin A was isolated by virtue of its ability to increase the catalytic rate of transcript elongation by RNA polymerase II in vitro [16]. Binding of the other components of the complex, Elongin B and C, increases the specific activity of Elongin A. The F-box motif of Elongin A is in the smallest region shown to be sufficient for Elongin A to bind Elongin C in both yeast and humans [17,18]. Elongin C has homology to Skp1; the F-box-Elongin C interaction may therefore be evolutionarily conserved."

"In order to examine the factors involved in regulating telomere length homoeostasis, Liu et al.²⁵ carried out a genome-wide screen of deletion mutations that impacted telomere length in S. pombe²⁵. Deletion of 168 genes was found to alter telomere length, with four causing ‘very short’ telomeres (>150 bp shorter than wild type). These were est1, trt1 and ccq1, which are essential for telomerase activity, and pof8, of unknown function. Pof8 is a putative F-box protein, which bind to Skp1 and Cullin to form an SCF E3 ubiquitin ligase complex²⁶. Previous studies identified Pof8 as a Skp1 binding protein but the association with Cullin was not determined^27,28, implying a function distinct from a canonical F-box protein. Here we redefine Pof8 as an RNA-binding protein of the ancient LARP7 family (Laribonucleoprotein domain family member 7 or La-related protein 7) and thus rename it Lar7. LARP7 proteins are characterised by an N-terminal RNA-binding domain termed a La-motif and two RNA-recognition motifs (RRMs). LARP7 proteins associate with non-coding RNAs transcribed by RNA polymerase III, which have a hallmark 3′-UUU-OH tag²⁹. Here we report that Lar7 interacts with TER1 and plays a crucial role during its biogenesis. Lar7 stabilises the interaction between TER1 and the Lsm2–8 complex and facilitates assembly with Trt1. Loss of Lar7 leads to disassembly of telomerase and exosomal degradation of TER1, resulting in impaired telomerase activity and maintenance of very short telomeres. Further, we report a high degree of conservation between Lar7 and both the human protein hLARP7 and Tetrahymena thermophila telomerase RNA-binding protein p65. In human cells, loss of hLARP7 has recently been shown to cause telomere shortening³⁰. Thus, LARP7-familiy proteins are universally crucial for telomere maintenance."

"Lar7 is a member of the LARP7 RNA-binding protein family. In order to assess the function of Lar7 in telomere biology, we first analysed its predicted structure for key domains or moieties that may allude to its function. Using the bioinformatics tool HHpred (homology detection and structure prediction by HMM-HMM) and the Protein Homology/Analogy Recognition Engine v2.0 (Phyre2)^33,34, we identified two likely RNA-recognition motifs (RRMs), which have the format β1-α1-β2-β3-α2-β4, in four fission yeast species [...]. Additionally, we identified structural similarity between Lar7 and the human protein hLARP7 (La-related protein 7 or La ribonucleoprotein domain family member 7), which is part of the wider LARP7 family of non-coding RNA-binding proteins³⁵. Remarkably, a well-described member of this family and orthologue of hLARP7 is the telomerase-binding protein p65 in ciliate T. thermophila. All LARP-family proteins (including hLARP7 and p65) have a conserved N-terminal La-motif followed by an RRM (together termed the ‘La-module’) and a second RRM toward the C-terminus [...]. The alignment of S. pombe Lar7 with p65 and hLARP7 and a comparison of Lar7 with the published structures of hLARP7 and p65^36–38 revealed considerable sequence and structural similarity between the three proteins [...]. The reported secondary structure of a La-motif is α1-β1-α2-α3-β2-β339. According to the HHpred analysis, the N-terminus of S. pombe Lar7 corresponds to this predicted structure (amino acids 64–138), preceding RRM1 (amino acids 148–230). We have therefore assigned this region a La-motif. Interestingly, the domain assigned as an F-box in Lar7 (amino acids 66–106^27,28) lies within the La-motif. Due to this striking conservation and the criteria defining LARP7 family proteins²⁹, in addition to the function of Lar7 in telomerase RNA binding (defined in this report), we concluded that the annotated Pof8 is a member of the LARP7 family and accordingly renamed it Lar7 (La-related protein 7)."

F box genes

Gene ID: 22992 is KDM2A lysine demethylase 2A on 11q13.2: "This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants."

1. NP_001243334.1 lysine-specific demethylase 2A isoform b: "Transcript Variant: This variant (3) lacks several 5' exons but contains an alternate 5' exon, uses an internal downstream promoter, and differs in its 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (b, also known as SF-KDM2A or short-form KDM2A) has a distinct and shorter N-terminus, compared to isoform a."
2. NP_036440.1 lysine-specific demethylase 2A isoform a: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a)."

Gene ID: 23194 is FBXL7 F-box and leucine rich repeat protein 7 on 5p15.1: "This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene."

1. NP_001265246.1 F-box/LRR-repeat protein 7 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 2 which is shorter at the N-terminus compared to isoform 1."
2. NP_036436.1 F-box/LRR-repeat protein 7 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

See also

• A1BG gene transcriptions
• H box gene transcription laboratory