The reference OMIM entry for this protein is 612598

Ring finger protein 11; rnf11

CLONING

By searching an EST database for sequences similar to mouse Rnf11, followed by screening a fetal brain cDNA library, Seki et al. (1999) cloned human RNF11. Both mouse and human RNF11 contain 144 amino acids, and they differ at only 1 amino acid. Northern blot analysis detected Rnf11 expression in all mouse tissues and embryonic stages examined. RT-PCR showed ubiquitous expression in human tissues. Using subtractive hybridization and differential display with matched normal and breast tumor cell lines, followed by RT-PCR, Kitching et al. (2003) cloned full-length RNF11 and a possible splice variant. The deduced full-length 154-amino acid protein contains a potential WW domain-binding PPPPY motif in its N-terminal region, followed by potential SH2 domain-binding sites and a C-terminal RING-H2 domain. Northern blot analysis detected highest expression in skeletal muscle, followed by testis, heart, brain, and placenta. All other tissues examined showed weaker RNF11 expression. Immunohistochemical analysis showed that RNF11 was cytosolic, with higher expression in breast cancer cells than in normal breast epithelial cells. By Northern blot analysis of human brain regions, Anderson et al. (2007) detected highest expression of the 2.4-kb RNF11 transcript in amygdala, with moderate to low expression in other regions. Immunohistochemical analysis of rat and human brain showed that RNF11 was variably expressed in neurons and was excluded from white matter.

GENE FUNCTION

Using protein pull-down assays, Kitching et al. (2003) showed that AIP4 (ITCH; 606409), an E3 ubiquitin ligase, interacted with endogenous RNF11 from breast tumor cells lines and with epitope-tagged RNF11 expressed in human embryonic kidney cells. The interaction required the PY motif of RNF11 and the first WW domain of AIP4. Subramaniam et al. (2003) found that the RNF11 protein was overexpressed in invasive breast cancers and more weakly expressed in kidney and prostate tumors. Using protein pull-down and immunoprecipitation assays, they found that RNF11 interacted with the E3 ubiquitin ligase SMURF2 (605532), leading to ubiquitination of both proteins. The interaction required the PY motif of RNF11 and WW domains 2 and 3 of SMURF2. RNF11 also interacted with the ubiquitin-conjugating protein UBCH5 (UBE2D1; 602961), but not with UBC3 (CDC34; 116948), and ubiquitination of RNF11 by SMURF2 required the PY motif. SMURF2 represses TGF-beta (TGFB1; 190180) signaling, and Subramaniam et al. (2003) showed that RNF11 relieved SMURF2-mediated transcriptional inhibition of a TGF-beta-responsive promoter in reporter gene assays in a manner dependent on its PY motif. Using RNF11 as bait in a yeast 2-hybrid screen of a human ovary cDNA library, Li and Seth (2004) showed that human RNF11 interacted with ZBRK1 (ZNF350; 605422), EPS15 (600051), and AMSH (STAMBP; 606247). The interaction of RNF11 with AMSH was independent of the RNF11 RING finger domain and PY motif. AMSH was ubiquitinated by SMURF2 in the presence of RNF11, and reduction in the steady-state level of AMSH required both RNF11 and SMURF2. Li and Seth (2004) concluded that RNF11 recruits AMSH to SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome. Connor et al. (2005) showed that AKT (see 164730) phosphorylated RNF11 on thr135, which is located within a 14-3-3 (see 113508)-binding motif within the C-terminal RING finger domain of RNF11. RNF11 showed enhanced binding to 14-3-3 in ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 612598 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).