Disease relevance of TRIM17

• RBCK1 (RBCC protein interacting with PKC 1) has originally been identified as a protein kinase CbetaI (PKCbetaI)-binding partner by a two-hybrid screen and as one of the gene transcripts that increases during adult cardiac hypertrophy [1].
• Despite low identity within the RBCC domain, all fusion proteins were found to restrict HIV-1 but not the nonbinding G89V mutant, indicating that the overall structure of RBCC and not its primary sequence was important for the restriction function [2].
• Ro52, one of the major autoantigens in the rheumatic disease Sjögren's syndrome (SS), belongs to the tripartite motif (TRIM) or RING-B-box-coiled-coil (RBCC) protein family, thus comprising an N-terminal RING, followed by a B-box and a coiled-coil region [3].

High impact information on TRIM17

• MUL is ubiquitously expressed and encodes a new member of the RING-B-box-Coiled-coil (RBCC) family of zinc-finger proteins, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis [4].
• Subclassification of the RBCC/TRIM superfamily reveals a novel motif necessary for microtubule binding [5].
• Further bioinformatics investigation permitted subclassification of the entire human RBCC complement into nine subfamilies based on their varied C-terminal domain compositions [5].
• A novel matrix-assisted laser desorption ionization time-of-flight mass spectrometry strategy for time-resolved proteolysis experiments of large protein domains was developed to facilitate analysis and to help resolve the tertiary arrangement of the entire RBCC subregion [6].
• This suggests that a large number of tripartite motif family members sharing the RBCC moiety may participate in the control of cell survival [7].

Biological context of TRIM17

• Several RBCC proteins, such as PML, TIF1alpha and RFP, have transformation capabilities when found in chromosomal translocations [8].
• These results provide additional evidence that the mouse 11B region displays conserved linkage homology with the rat 10q22 region, whereas in the case of RNF16, this homology is only conserved among rodents, distinct from the 1q42 region of the human genome [9].
• Although RFP is known to become oncogenic when its RBCC moiety is connected to a tyrosine kinase domain by DNA rearrangement, its biological function is not well defined [7].
• The locations of exon/intron boundaries correlated well with those for the regions of conserved amino acid sequences (RBCC motif, PHD finger and bromodomain) [10].
• As a structural feature, the RNF21 cDNA possessed at least three kinds of isoforms, due to alternative splicing, consisting of the long form with the RBCC-RBCC-B30.2 domain, the medium form with the RBCC-B30.2 domain, and the short form with only the RBCC domain [11].

Anatomical context of TRIM17

• Then, the human homologue of the terf cDNA was also isolated from a testis library [8].
• Human RNF16 is located at 1q42 based on PCR-assisted analysis of both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid-mapping panel [9].
• Previously, we isolated a novel haploid-germ-cell-specific gene in the mouse; this gene, named haprin, encodes the RING-finger, B-box-type zinc finger and coiled-coil domain (RBCC) motif protein and may be involved in the acrosome reaction [12].

Analytical, diagnostic and therapeutic context of TRIM17

• Molecular cloning of a novel RING finger-B box-coiled coil (RBCC) protein, terf, expressed in the testis [8].
• This gene was designated testis RING finger protein (terf) because the corresponding transcripts were detected almost exclusively in the testis by Northern blot analysis [8].
• Immunofluorescence confocal microscopy indicated that MUL localizes to cytosolic bodies, with targeting to these structures mediated by a RBCC tripartite domain within the MUL protein [13].
• A combination of gel filtration, analytical ultracentrifugation, chemical cross-linking, non-denaturing gel electrophoresis, and site-directed mutagenesis techniques has revealed that the KAP-1-RBCC must oligomerize likely as a homo-trimer in order to bind the KRAB domain [14].
• Nrdp1 belongs to the tripartite or RBCC (RING, B-box, coiled-coil) family of ubiquitin ligases in which the RING domain is responsible for ubiquitin ligation and a variable C-terminal region mediates substrate recognition [15].

References