Recombinant Human E3 ubiquitin-protein ligase Arkadia (RNF111), Truncated

Uniprot Id

Q6ZNA4

Target Species

Human

Target Name

RNF111

Target Full Name

E3 ubiquitin-protein ligase Arkadia

Target Function

E3 ubiquitin-protein ligase. Required for mesoderm patterning during embryonic development. Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP. In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded. Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL. Associates with UBE2D2 as an E2 enzyme. Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates. Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair. Mediates ubiquitination and degradation of sumoylated PML. The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs).

Target Subcellular Location

Nucleus. Cytoplasm. Nucleus, PML body.

Target Protein Families

Arkadia family

Target Tissue Specificity

Broadly expressed.

Target Synonyms

RNF111; E3 ubiquitin-protein ligase Arkadia; EC 2.3.2.27; RING finger protein 111; hRNF111; RING-type E3 ubiquitin transferase Arkadia

Target Background

The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.