Disease relevance of RNF6

• Identification of somatic mutations of the RNF6 gene in human esophageal squamous cell carcinoma [1].
• We report here the cloning of RNF6, a new gene that maps close to the chromosome 13 breakpoint in a case of myelofibrosis with a t(4;13)(q26;q12) [2].
• We expressed the EL5 RING-H2 finger domain in Escherichia coli and determined its structure in solution by NMR spectroscopy [3].
• The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase [4].

High impact information on RNF6

• SCF and Cullin/Ring H2-based ubiquitin ligases [5].
• Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins [6].
• The regions of similarity among the UBR family members include a putative zinc finger and RING-H2 finger, another zinc-binding domain [7].
• Identification of multiple somatic mutations in RNF6 suggests that RNF6 is a potential tumor suppressor gene involved in the pathogenesis of ESCC [1].
• In contrast, three somatic mutations in the RNF6 gene were detected in the ESCC primary tumors, and one mutation was also found in a tumor cell line [1].

Biological context of RNF6

• FISH and physical mapping indicated that RNF6 is located at 13q12.2 close to marker D13S1121, and it is oriented from telomere to centromere [2].
• We conclude that the RING-H2 finger domain of EL5 is the E2 binding site of EL5 [3].
• We introduced point mutations into the EL5 RING-H2 finger so that residues that functionally interact with OsUBC5b could be identified when assayed for ubiquitination activity in vitro [8].
• Both genes encode a protein of 643 amino acids containing a seven transmembrane domain, a RING-H2 motif and a leucine zipper motif and showed a 94.7% amino acid sequence identity to each other [9].
• The expression of LeATL6, an ortholog of Arabidopsis ATL6 that encodes a RING-H2 finger protein, was induced in tomato roots treated with a cell wall protein fraction (CWP) elicitor of the biocontrol agent Pythium oligandrum [10].

Anatomical context of RNF6

• Goliath, a ring-H2 mitochondrial protein, regulated by luteinizing hormone/human chorionic gonadotropin in rat leydig cells [11].
• Disruption of the Ring-H2 finger motif does not affect the cellular localization of CKBBP1 in HeLa cells [12].
• The regulation of the TGF-beta pathway through a PRAJA, a RING finger (RING-H2) protein, and ELF, a beta-Spectrin adaptor protein, both which were originally identified in endodermal stem/progenitor cells committed to foregut lineage, could play a pivotal role in gastric carcinogenesis [13].

Associations of RNF6 with chemical compounds

• APC11 contains a RING-H2-finger domain, which includes one histidine and seven cysteine residues that coordinate two Zn(2+) ions [14].
• The domains that interacted with ANAC contain a glutamic acid residue in a position corresponding to a proline in many RING-H2 domains [15].
• A variant of the RING domain is the RING-H2 domain, in which one of the cysteines is replaced by a histidine [16].
• We cloned human and mouse entire kf-1 cDNAs encoding conserved 79 kDa proteins containing a zinc-binding RING-H2 finger motif at the carboxy-terminus as found in acetylcholine receptor-associated protein (RAPsyn) [17].

Physical interactions of RNF6

• Active site residues and amino acid specificity of the ubiquitin carrier protein-binding RING-H2 finger domain [8].

Other interactions of RNF6

• Our laboratory has found that the 154aa RING finger protein 11 (RNF11), has modular domains and motifs including a RING-H2 finger domain, a PY motif, an ubiquitin interacting motif (UIM), a 14-3-3 binding sequence and an AKT phosphorylation site [18].
• A double RING-H2 domain in RNF32, a gene expressed during sperm formation [16].
• hRUL138, a novel human RNA-binding RING-H2 ubiquitin-protein ligase [19].
• hVPS41 is expressed in multiple isoforms and can associate with vesicles through a RING-H2 finger motif [20].
• Molecular cloning and characterization of a RING-H2 finger protein, ANAPC11, the human homolog of yeast Apc11p [21].

Analytical, diagnostic and therapeutic context of RNF6

• Cloning and characterization of RNF6, a novel RING finger gene mapping to 13q12 [2].
• The residue positions were selected based on the results of an EL5 RING-H2 finger/OsUBC5b NMR titration experiment [8].
• Site-directed mutagenesis analysis identifies RING-H2 finger residues Cys(42), Cys(45), Cys(75), His(77), His(80), Cys(83), Cys(94), and Asp(97) as being essential for the ROC1-dependent ubiquitin ligase activity [22].
• Here we present evidence suggesting that a conserved RING-H2 structure within ROC1 is critical for its ubiquitin ligation function [22].

References